Membrane potential
n Electrical potential exist across cell membrane
n Generates electrochemical impulses
Membrane potential caused by diffusion
n K concentration is very great inside the cell
n K concentration is very low outside the cell
n Assume that the membrane is permeable only to k
n Concentration gradients dictates K to diffuse out
n K carry + charges resulting to electropositvity outside and electronegativity inside
n Thus concentration difference of ions across a permeable membrane cause the membrane potential
Diffusion potential and concenetration difference
n Nearnst potential –potential level across the membrane that prevents diffusion of the ion in either direction
- measured by the ratio of ion concentration
from two sides of the membrane
n Nearnst potential
n EMF(millivolts) = +61 log conc. I
______
conc. O
n Calculated potential is the potential inside the cell
n When the membrane is permeable to other ions
the diffusion potential that develops depend
on the following:
1. polarity of the electrical charge
2. permeability of the membrane
3. concentration of the respective ions in
and out of the membrane
n Goldman hogkin katz equation
Resting membrane potential of a nerve
n membrane potential of a large nerve = -90m
n Origin of membrane potential
1. from the K diffusion potential = -94mv
2.from the Na diffusion potential = +61mv
considering both with goldman equation
= -86mv
3.from Na and K pump = -4mv
Nerve action potential
n Rapid changes in the membrane potential
n Conduction of nerve signal
n Stages of action potential
1.resting stage- membrane is polarized
- negative membrane potential
2. depolarization stage – membrane becomes
permeable to Na
- polarized state is lost
3. repolarization stage – Na channel closes
- K channel opens
Voltage gated sodium and potassium channel
n Role in causing action potential
n Voltage gated Na channel has 2 gates
1. activation gate
2. inactivation gate
- at resting state(-90mv) activation gate is closed
and inactivation gate is open
- when membrane potential becomes less negative
(-70 to -50mv) conformational change in
activation gate open Na flow toward inside
- this is the activated state
n Inactivation of Na channel
n Closure of the inactivation gate follows a few 10,000th of a second after the activation gate is open
Role of other ions during action potential
n 1. impermeant negatively charged ions inside the axon
-protein molecules, organic and phosphate compounds
-deficit in positive ions inside the membrane leave an
excess negatively charged ion
n Increase permeability of Na channels when there is deficit of calcium ions
-Na channels are activated by very little increase of
membrane potential above normal level – highly
excitable state tetany
- calcium ions binds with exterior surface of Na channel
increasing the requirement to open the gate
n 3.chloride ions
- leak channel
- passive role
Initiation of action potential
n Any rise in membrane potential
n Opening of the voltage gated Na channel
Threshold for action potential
n Sudden rise of membrane potential by
15 to 30mv
n Threshold for stimulation is -65mv
Accommodation of the membrane
n Failure to fire despite rising voltage
n Very slow rise in membrane potential
n Inactivating gates will have time to close at the
same time that the activating gates are opening
n Ineffective Na flow
Propagation of action potential
n Excitation of adjacent area
n Transmission of depolarization along nerve
or muscle IMPULSE
n Direction of depolarization all branches
of nerve fiber
all or nothing principle
n Once an action potential has been elicited at any
point on the membrane, the depolarization
process will travel over entire membrane if
the conditions are right or it might not travel
at all if conditions are not right
n Safety factor for propagation
Initiation and excitation of action potential
n Any factor causing Na diffusion
n Mechanical
n Chemical
n Electrical
n Threshold for initiation of action potential
- rise in membrane potential of 15-30mv
- -65mv ---- threshold for stimulation
Plateau in some action potential
n Membrane does not repolarize immediately after
depolarization--- heart muscle
n causes: 2 types of channel
1.fast channel – v gated Na channel
2.slow channel – allows diffusion mostly calcium but
also Na
--activation of fast channel causes spike portion
-- slow but prolonged activation of slow channel is responsible for plateau
-- v-gated K channel are slowly activated sometimes – delays the return
of membrane potential
rhythmicity of action potential
n Repetitive discharge
n Heart muscle, smooth muscle, neurons of CNS
n Reexcitation process – resting membrane must already be
permeable enough to Na ions
n Resting membrane potential of -60 to -70mv not enough to
keep the Na channel and Ca channel closed
special aspect of action potential
n Myelinated and unmyelinated fibers
n Myelin sheath is deposited around axon by Schwann cell
n Sphyngomyelin – excellent insulator
n Node of Ranvier – uninsulated areas
n Saltatory conduction in myelinated fibers
n Value of saltatory conduction
1. increases velocity of nerve conduction
2. conserve energy
3. allows repolarization process to occur with very
little transfer of ions
excitation
n Any factor that can cause Na ion influx
n Maybe mechanical, chemical or electrical factor
n Decrease in electrical voltage across membrane
n Threshold for excitation and acute local potentials
-a weak stimulus may not be able to excite a fiber
- progressive increased in stimulus will reach a point when
excitation does take place
inhibition of excitability
n Stabilizers and local anesthesia
n Decrease membrane excitability
n Increase extracellular calcium
n Decrease extracellular calcium level
n Local anesthesia makes activation gate difficult to open
Wednesday, January 30, 2008
slide smooth m
Smooth muscle
Responsible for the contractility of hollow organs
blood vessel
gastrointestinal tract
uterus
urinary bladder
smooth muscle contraction
Small fibers
Skeletal fibers 20 times bigger ,thousand times longer
Same principles of contraction
Differ in physical arrangement
Types of smooth muscle
A. MULTIUNIT SMOOTH MUSCLE
B. SINGLE UNIT SMOOTH MUSCLE
A. multiunit smooth muscle
-discrete muscle fibers
-each fiber operates independently
-Innervated by a single nerve ending
-covered by basement-like membrane substances
-control by nerve signal
-rarely exhibit spontaneous contraction
-ciliary muscle of the eye
-iris of the eye
B. single unit smooth muscle
-group of muscle fibers that contract together as a single
unit
-aggregated into sheets or bundles
-cell membranes are adherent
-impulse generated at one fiber can be transmitted to the
next fiber
-gap junction—thru which ion can flow from one cell to
the other
-syncitial smooth muscle : visceral sm m.– walls of most
viscera
contraction process
Chemical basis – actin and myosin but no troponin
Physical basis – actin attached to dense bodies
- dense bodies are attached to the
cell membranes and other structural
proteins linking them to one another
- myosin filamints are sparsely seen
- less regularity that is characteristics of
skeletal muscle
comparison of smooth and skeletal m
Skeletal muscle contraction – rapid
Smooth m. contraction – prolonged and sustained
Slow cycling of cross bridges – 1/10 to 1/300 the frequency
of skeletal m.
- myosin head lacks ATPase activity
- fraction of time of attachment of cross bridges
actin filamints is increased
Energy required to sustain smooth m. contraction:
only 1/10 to 1/300 in skeletal m.
Slowness of onset of contraction and relaxation:
- contracts 50 to 100 millisec.after it is
excited
- reaches full contraction ½ sec. later
- contraction time of 1 to 3 sec.(30x longer)
- due to slow cycling of cross bridges
Force of contraction – 4 -6 kg/cm2
Percentage of shortening of smooth m. during contraction –
- greater percentage of shortening while maintaining
full force of contraction
-important in function of hollow viscus
due to: 1. optimal overlapping of filamints
2. longer actin filamints
Prolonged holding contraction
The latch mechanism:
once the muscle has developed full contraction the
degree of activation of the muscle can be reduced to less
than the initial level
at the same time the muscle maintain its full strength
of contraction
- responsible for the prolonged tonic with minimal
energy utilization
- little excitatory signal is required
- due to prolonged attachment of filaments
Stress relaxation of smooth m
Ability to return to its original force of contraction seconds after it has been elongated or stretched
example; urinary bladder
Related to latch phenomenon
Regulation of contraction
Initiating event for contraction is increase in intracellular calcium
Increase of calcium by:
1.nervous stimulation
2.hormonal stimulation
3.mechanical factor such as stretch
4. changes in chemical environment
Mechanism of contraction
NO troponin thus different mechanism thru calmodulin
1. calmodulin binds with calcium
2. complex activates myosin kinase
3.one of the light chains of the myosin head(regulatory)
becomes phosphorylated
4. phosphorylation start binding of myosin head with
actin thus cycling process occurs
Cessation of contraction is due to
- myosin phosphatase
- splits phosphate from regulatory chain
Myosin kinase and myosin phosphatase may explain the latch phenomenon
Neural and hormonal regulation of contraction
Skeletal muscle is activated exclusively by nervous system
Smooth m. can be stimulated by
nervous
hormonal stimuli and other ways
Presence of receptor proteins in the cell membrane
Some are inhibitory receptors
Neuromuscular junction of smooth m
Terminal axon has varicosities which contain transmitter substances
Transmitter substances– acetylcholine and norepinephrine both can either be inhibitory or excitatory depending on the receptor protein
Membrane and action potential in smooth m
Value is variable from one type to the other
Usually between -50 to -60millivolts
Action potentials occur in single unit smooth m. the same way as in skeletal m.
Action potential occurs in single unit smooth m.
the same way in skeletal muscle
Action potential do not normally occur in many
or most of the multiunit type
2 types of potential in smooth m
1. spike potential
2. action potential with plateau
Spike potential
Such as those seen in skeletal m.
Can be seen in most single unit smooth m.
Can be elicited by:
1. electrical stimulation
2. hormonal stimulation
3. transmitter substance
4. spontaneous generation
Action potential with plateaus
Onset is similar to spike potential
Repolarization is delayed by several hundreds
to thousands of milliseconds
Important in prolonged contraction like:
ureter
uterus
other vascular smooth muscle
calcium channel in action potential
Cell membrane of smooth m. has more calcium channel and few sodium channel
Very little sodium participation
Influx of calcium is responsible for potential generation
Calcium channels open more slowly than sodium channel
Slow action potential
Calcium entry into the cell can act directly on the contracting mechanism
Slow wave potentials in single unit smooth muscle and spontaneous genearation of action potential
Some smooth muscle are self excitatory
Due to basic slow wave rhythm of membrane
potential
Slow wave itself is not an action potential but a local
property of smooth muscle fibers
slow potential
Cause of slow wave
1. waxing and waning of pumping of sodium
2. rhythmical increase and decrease of ionic
conductance
Importance of slow wave is that it can initiate action
potential thus also known as pacemaker waves
excitation of smooth m by stretch
When single unit smooth m. is stretched this results
to spontaneous generation of action potential
Due to normal slow wave and decrease in the
negativity of the membrane cause by the stretch
itself
Response of the hollow organ to resist stretch as
seen in the gut
depolarization of smooth m without action potential
Normally contract mainly in response to nerve stimuli
Nerve endings release transmitter substances
Half or most of all smooth m. contraction is initiated
not by action potentials but by stimulatory factors
acting directly on smooth muscle machinery
The 2 factors are
1. local tissue factors
2. various hormones
Local tissue factors
Contraction of arterioles and meta-arterioles and
precapillary sphincter as respond to rapidly changing condition in the interstitial fluid
specific control factors
1.lack of O2 in the local tissue –smooth m.relaxation
2.excess CO2 – vasodilatation
3.increased hydrogen ion conc.- vasodilatation
Hormonal factors
Norepinephrine, epinephrine,acetylcholine,
Angiotensin,oxytocin, serotonin and histamine
Hormone can cause contraction if the membrane contains hormone-gated excitatory receptor and inhibition if receptor is inhibitory
Smooth m contraction
Some hormone receptors in smooth m. open sodium
or calcium channels thus depolarization
Sometime action potential result
Enhance rhythmical action potential
Mostly no action potential into the cell
Calcium ion entry into the cell promotes contraction
Activation of some membrane receptors inhibits contraction
-due to closing of the sodium or calcium channel
-opening of the potassium channels resulting to
efflux of K ion increasing negativity inside—
HYPERPOLARIZATION
Sometimes contraction or inhibition is initiated by hormones without change in the membrane potential
-hormone activates a membrane receptor that does
open ion channel but causes an internal change
in muscle fiber: release of calcium ion
- activating enzymes like adenyl cyclase resulting
AMP as second messenger-inhibition of contraction
by affecting calcium pump in sarcoplasmic and
cell membrane
source of calcium ions
Both through the cell membrane and sarcoplasmic
reticulum
Source of calcium ions differ from that of skeletal m.
Sarcoplasmic reticulum is a rudimetary structure in
most of smooth m.
Most calcium ions in smooth m. comes from extra
cellular fluid
Because smooth m. fibers are small – calcium can
diffuse to all parts of the fiber causing contraction
Calcium can also enter inside the m. fiber through
hormone activated calcium channel
Calcium may not cause action potential because of
sodium pump but contraction can proceed
role of sarcoplamic reticulum
Moderately developed in some fibers
Situated close to the cell membrane invagination-
calveoli
Calveoli represents the T tubules in the skeletal m.
The more extensive the sarcoplasmic reticulum in the
smooth m. the faster it can contract
effect of extracellular calcium ion
Low concentration results to weakened muscular contraction
Calcium pump
In cell membrane
In organelle membrane
Removal of calcium ions result in relaxation of
contractile filamints
Calcium pump in smooth m. is slow acting –
longer duration of contraction
neural and hormonal control of smooth m contraction
Skeletal muscle is activated exclusively by nervous
system
Smooth m. can be stimulated by nervous and
hormonal stimuli and other ways
Presence of receptor proteins in the cell membrane
Some are inhibitory receptors
Responsible for the contractility of hollow organs
blood vessel
gastrointestinal tract
uterus
urinary bladder
smooth muscle contraction
Small fibers
Skeletal fibers 20 times bigger ,thousand times longer
Same principles of contraction
Differ in physical arrangement
Types of smooth muscle
A. MULTIUNIT SMOOTH MUSCLE
B. SINGLE UNIT SMOOTH MUSCLE
A. multiunit smooth muscle
-discrete muscle fibers
-each fiber operates independently
-Innervated by a single nerve ending
-covered by basement-like membrane substances
-control by nerve signal
-rarely exhibit spontaneous contraction
-ciliary muscle of the eye
-iris of the eye
B. single unit smooth muscle
-group of muscle fibers that contract together as a single
unit
-aggregated into sheets or bundles
-cell membranes are adherent
-impulse generated at one fiber can be transmitted to the
next fiber
-gap junction—thru which ion can flow from one cell to
the other
-syncitial smooth muscle : visceral sm m.– walls of most
viscera
contraction process
Chemical basis – actin and myosin but no troponin
Physical basis – actin attached to dense bodies
- dense bodies are attached to the
cell membranes and other structural
proteins linking them to one another
- myosin filamints are sparsely seen
- less regularity that is characteristics of
skeletal muscle
comparison of smooth and skeletal m
Skeletal muscle contraction – rapid
Smooth m. contraction – prolonged and sustained
Slow cycling of cross bridges – 1/10 to 1/300 the frequency
of skeletal m.
- myosin head lacks ATPase activity
- fraction of time of attachment of cross bridges
actin filamints is increased
Energy required to sustain smooth m. contraction:
only 1/10 to 1/300 in skeletal m.
Slowness of onset of contraction and relaxation:
- contracts 50 to 100 millisec.after it is
excited
- reaches full contraction ½ sec. later
- contraction time of 1 to 3 sec.(30x longer)
- due to slow cycling of cross bridges
Force of contraction – 4 -6 kg/cm2
Percentage of shortening of smooth m. during contraction –
- greater percentage of shortening while maintaining
full force of contraction
-important in function of hollow viscus
due to: 1. optimal overlapping of filamints
2. longer actin filamints
Prolonged holding contraction
The latch mechanism:
once the muscle has developed full contraction the
degree of activation of the muscle can be reduced to less
than the initial level
at the same time the muscle maintain its full strength
of contraction
- responsible for the prolonged tonic with minimal
energy utilization
- little excitatory signal is required
- due to prolonged attachment of filaments
Stress relaxation of smooth m
Ability to return to its original force of contraction seconds after it has been elongated or stretched
example; urinary bladder
Related to latch phenomenon
Regulation of contraction
Initiating event for contraction is increase in intracellular calcium
Increase of calcium by:
1.nervous stimulation
2.hormonal stimulation
3.mechanical factor such as stretch
4. changes in chemical environment
Mechanism of contraction
NO troponin thus different mechanism thru calmodulin
1. calmodulin binds with calcium
2. complex activates myosin kinase
3.one of the light chains of the myosin head(regulatory)
becomes phosphorylated
4. phosphorylation start binding of myosin head with
actin thus cycling process occurs
Cessation of contraction is due to
- myosin phosphatase
- splits phosphate from regulatory chain
Myosin kinase and myosin phosphatase may explain the latch phenomenon
Neural and hormonal regulation of contraction
Skeletal muscle is activated exclusively by nervous system
Smooth m. can be stimulated by
nervous
hormonal stimuli and other ways
Presence of receptor proteins in the cell membrane
Some are inhibitory receptors
Neuromuscular junction of smooth m
Terminal axon has varicosities which contain transmitter substances
Transmitter substances– acetylcholine and norepinephrine both can either be inhibitory or excitatory depending on the receptor protein
Membrane and action potential in smooth m
Value is variable from one type to the other
Usually between -50 to -60millivolts
Action potentials occur in single unit smooth m. the same way as in skeletal m.
Action potential occurs in single unit smooth m.
the same way in skeletal muscle
Action potential do not normally occur in many
or most of the multiunit type
2 types of potential in smooth m
1. spike potential
2. action potential with plateau
Spike potential
Such as those seen in skeletal m.
Can be seen in most single unit smooth m.
Can be elicited by:
1. electrical stimulation
2. hormonal stimulation
3. transmitter substance
4. spontaneous generation
Action potential with plateaus
Onset is similar to spike potential
Repolarization is delayed by several hundreds
to thousands of milliseconds
Important in prolonged contraction like:
ureter
uterus
other vascular smooth muscle
calcium channel in action potential
Cell membrane of smooth m. has more calcium channel and few sodium channel
Very little sodium participation
Influx of calcium is responsible for potential generation
Calcium channels open more slowly than sodium channel
Slow action potential
Calcium entry into the cell can act directly on the contracting mechanism
Slow wave potentials in single unit smooth muscle and spontaneous genearation of action potential
Some smooth muscle are self excitatory
Due to basic slow wave rhythm of membrane
potential
Slow wave itself is not an action potential but a local
property of smooth muscle fibers
slow potential
Cause of slow wave
1. waxing and waning of pumping of sodium
2. rhythmical increase and decrease of ionic
conductance
Importance of slow wave is that it can initiate action
potential thus also known as pacemaker waves
excitation of smooth m by stretch
When single unit smooth m. is stretched this results
to spontaneous generation of action potential
Due to normal slow wave and decrease in the
negativity of the membrane cause by the stretch
itself
Response of the hollow organ to resist stretch as
seen in the gut
depolarization of smooth m without action potential
Normally contract mainly in response to nerve stimuli
Nerve endings release transmitter substances
Half or most of all smooth m. contraction is initiated
not by action potentials but by stimulatory factors
acting directly on smooth muscle machinery
The 2 factors are
1. local tissue factors
2. various hormones
Local tissue factors
Contraction of arterioles and meta-arterioles and
precapillary sphincter as respond to rapidly changing condition in the interstitial fluid
specific control factors
1.lack of O2 in the local tissue –smooth m.relaxation
2.excess CO2 – vasodilatation
3.increased hydrogen ion conc.- vasodilatation
Hormonal factors
Norepinephrine, epinephrine,acetylcholine,
Angiotensin,oxytocin, serotonin and histamine
Hormone can cause contraction if the membrane contains hormone-gated excitatory receptor and inhibition if receptor is inhibitory
Smooth m contraction
Some hormone receptors in smooth m. open sodium
or calcium channels thus depolarization
Sometime action potential result
Enhance rhythmical action potential
Mostly no action potential into the cell
Calcium ion entry into the cell promotes contraction
Activation of some membrane receptors inhibits contraction
-due to closing of the sodium or calcium channel
-opening of the potassium channels resulting to
efflux of K ion increasing negativity inside—
HYPERPOLARIZATION
Sometimes contraction or inhibition is initiated by hormones without change in the membrane potential
-hormone activates a membrane receptor that does
open ion channel but causes an internal change
in muscle fiber: release of calcium ion
- activating enzymes like adenyl cyclase resulting
AMP as second messenger-inhibition of contraction
by affecting calcium pump in sarcoplasmic and
cell membrane
source of calcium ions
Both through the cell membrane and sarcoplasmic
reticulum
Source of calcium ions differ from that of skeletal m.
Sarcoplasmic reticulum is a rudimetary structure in
most of smooth m.
Most calcium ions in smooth m. comes from extra
cellular fluid
Because smooth m. fibers are small – calcium can
diffuse to all parts of the fiber causing contraction
Calcium can also enter inside the m. fiber through
hormone activated calcium channel
Calcium may not cause action potential because of
sodium pump but contraction can proceed
role of sarcoplamic reticulum
Moderately developed in some fibers
Situated close to the cell membrane invagination-
calveoli
Calveoli represents the T tubules in the skeletal m.
The more extensive the sarcoplasmic reticulum in the
smooth m. the faster it can contract
effect of extracellular calcium ion
Low concentration results to weakened muscular contraction
Calcium pump
In cell membrane
In organelle membrane
Removal of calcium ions result in relaxation of
contractile filamints
Calcium pump in smooth m. is slow acting –
longer duration of contraction
neural and hormonal control of smooth m contraction
Skeletal muscle is activated exclusively by nervous
system
Smooth m. can be stimulated by nervous and
hormonal stimuli and other ways
Presence of receptor proteins in the cell membrane
Some are inhibitory receptors
Friday, January 25, 2008
cvs lymphatics lec slides
• Heart is composed of
• -3 major types of cardiac muslce
• 1. atrial muscle
• 2. ventricular muscle
• 3. excitatory and conductive muscle fibers(more of conductive function)
Cardiac muscle as a syncytium
• -presence of intercalated disc-
• --cell membrane separating individual muscle fibers
• ---offers easy diffusion of ions resulting in rapid spread of action potential to cardiac muscles---gap junction
• 2 syncitiums: atrial and ventricular
Action potential in cardiac muscle
• Resting membrane potential of
– -85 to -95mv in ventricular muscle
– -90 to -100mv in conductive fibers
– Shows spike potential followed by a plateau
– --due to fast channel and slow channel
• Contraction of cardiac muscle
• -excitation contraction coupling mechanism
• Extra calcium from T tubules (not only form SR)
• Regulation of heart pumping
• -at rest –pumps only 4 to 6 liters/min
• -severe exercise – pumps 4 to 7 times
• Regulation by
• 1. Intrinsic cardiac regulation
• 2. autonomic nervous system.
• Intrinsic regulation
• Frank-Starling mechanism
• --the more venous return the more blood is pump out to the systemic circulation
• --extra amount of blood in the ventricles stretch the muscle to its optimum interdigitation
• Sympathetic and parasympathetic regulation
• -sympathetic –excites the heart
• -parasympathetic(vagal) stimulation –depressed
• The normal electrocardiogram
• - reflection of cardiac impulse occuring thru the heart
• -electrical currents spread into the tissues surrounding the heart and some to the surface of the body
• Depolarization and repolarization waves
• --P wave is caused by electrical potentials generated as the atria depolarizes
• --QRS complex is caused by ventricular depolarization
• --T wave is caused by potentials generated as the ventricles recover from the state of depolarization(repolarization)
• Cardiac arrhythmias
• Due to
• 1. abnormal rhythmicity of the pacemaker
• 2. shift of the pacemaker from the sinus node to other parts of the heart
• 3. blocks at different points in the transmission of impulse through the heart
• 4. abnormal pathways of impulse transmission through the heart.
• 5. spontaneous generation of abnormal impulses in almost any part of the heart
Abnormal rhythms
• Tachycardia- faster than 100 beats/min
• --increased body temperature
• --stimulation of the heart by sympathetic nerves
• Bradycardia – less than 60 beats/min
• ---athletes
• --vagal stimulation
Abnormal rhythm resulting from impulse conduction block
• -atrioventricular block
• ----conditions causing decrease or total block of impulse conduction in the bundle of his
Premature contraction
• -contraction of the heart prior to the time that normal contraction would have been expected.
• ---caused by ectopic beat
• --premature atrial or ventricular contraction
Most serious of all cardiac arrhythmias
• -ventricular fibrillation--fatal
• --impulse have gone berserk resulting in uncoordinated, asynchronous and ineffective heart muscle contraction
• consequence--pumping action is impaired
• Causes
• -sudden electrical shock
• -ischemia of the heart
Electroshock of the ventricles
• -strong electrical current passed through the ventricles can stop fibrillation by throwing all ventricular muscle to refractory stage …all impulse stopped
• -after which the heart will begin to beat again from the SA node
Muscle blood flow and cardiac output during exercise
• Very strenuous exercise is the most stressful condition that the normal circulatory system faces
• -increase of more than 20 fold in blood flow to the muscle
• -1 liter/min to as great as 20 liters/min
• - increase in cardiac output to 5-6 times normal
Intermittent blood flow during muscle contraction
• -blood flow increases and decreases during contraction- relaxation and contraction phases
• -opening of muscle capillaries during exercise—during rest only 20-25% of muscle capillaries have flowing blood
• during strenuous exercise all capillaries open up—faster diffusion of oxygen from the capillaries to the muscle fiber
Control of blood flow through the skeletal muscles
1. Local effects in the muscles acting directly on the arterioles to cause vasodilatation
• -decrease in oxygen concentration
• -release of vasodilator substances
• -potassium ions,
• acetylcholine,
• adenosine triphosphate,
• lactic acid, and carbon dioxide
2.nervous control
• -presence of sympathetic vasoconstrictor nerves
• -release of norepinephrine
• -additional secretion of norepiniphrine and epinephrine from adrenal medullae
Circulatory readjustments during exercise
• 1. mass discharge of the sympathetic nervous system
• 2.increase in arterial pressure
• 3. increase cardiac output
The coronary circulation
• 1/3 of all deaths in the affluent society result from coronary artery disease
• Left coronary artery-
• --anterior and lateral portions of the left ventricle
• Right coronary artery-
• --most of the right ventricle and post. Part of left ventricle
Ischemic heart disease
• -atherosclerosis
• -most common site- first few centimeters of the coronary arteries
• -myocardial infarction
• --follows immediately after acute occlusion
• --area of muscle that has low or zero flow cant sustain muscle contraction
• Ischemic heart diseases
• -single most common cause of death in western culture
• -may cause sudden death due to acute coronary occlusion
• -or slow death over periods of weeks to years as a result of progressive weakening of heart pumping process
Causes of death following acute coronary occlusion
• 1. decrease cardiac output
• 2. damming of blood in the pulmonary circulation—resulting in edema
• 3.fibrillation of the heart
• 4. rupture of the heart
• Angina pectoris
• -cause is unknown but could be due to lactic acid, histamine kinins or proteolytic enzymes(not removed due to lost of circulation)
• Pain is felt in the chest, sternum, left arm and shoulder
• --trigger by exercise or emotional experience
Treatment for angina pectoris
• --vasodilators
• --beta blockers-blocks beta receptors which then prevents sympathetic stimulation of the heart that occurs during exercise and emotional episodes
• --surgical treatment
• ---aortic-coronary by-pass
• ---coronary angioplasty
Peripheral circulation
• The function of circulation is
• - to service the needs of the tissues
• -transport nutrients
• -waste products away,
• -to conduct hormones
• -maintain appropriate environment in all tissue fluids(maintain the internal ‘mellieu’)
Functional parts of circulation
• Arteries- transport blood under high pressure
• Arterioles – last, smallest branch of the arterial system, act as control valves through which blood is released to the capillaries
• Capillaries- for exchange of fluid –thus very thin and permeable to small molecular substances
• Venules- collects blood from capillaries
• -- reservoir of blood- low pressure and thin walls- keeps 84% of blood volume
Microcirculation and lymphatic system
• Where most purposeful function of he circulation occurs,
• -transport of nutrients to the tissues
• -removal of cellular excreta
Structure of the microcirculation
• Each nutrient artery entering an organ branches six to eight times before the arteries become small enough to be called arterioles
• Arterioles branch 2 to 5 times- capillaries
• Diameter of arterioles – 20 micrometer
• Diameter of capillaries-5 -9 micrometer
Pores in the capillary membrane
• - intercellular cleft- thin slit between endothelial cells in the capillaries
• - plasmalemmal vesicles- transport substance across endothelial cells
Flow of blood in the capillaries
• vasomotion
• -intermittent flow due to metaarteriole and precapillary sphincters –regulated by oxygen concentration
Exchange of nutrients between blood and interstitial fluid
• Diffusion
• -diffusion of lipid-soluble substances through the capillary membrane
• -diffusion of water-soluble substances through the capillary membrane
• Effect of molecular size on passage through the pores
• Effect of concentration difference on net rate of diffusion through the capillary membrane
The interstitium and the interstitial fluid
• -spaces between cells
• -collagen fibers and proteoglycan filamints
• - gel in the interstitium
• - rivulets
Distribution of fluid volume between the plasma and the interstitial fluid
• Four primary forces that determine fluid movement through the capillary membrane
• 1. capillary pressure – force fluid outward
• 2. Interstitial fluid pressure- force fluid inward
• 3.plasma colloid osmotic pressure- forced fluid inward
• 4. interstitial fluid colloid osmotic pressure -forces fluid outward
The lymphatic system
• Accessory route
• Carry proteins and large particulate matter
• Removal of protein from the interstitial space is essential without it can result in death
• Lymphatic channel of the body
• Lymph from the lower part of the body flows up the thoracic duct and empties into the venous system at the juncture of the left internal jugular vein and subclavian vein
• Lymph form left side of the head the left arm and parts of the chest region also enters the thoracic duct
• Lymph from the right side of the neck and head, from right arm and thorax- right subclavian vein
• Most fluid filtering from the arterial capillaries flows among the cells and is finally reabsorbed back into the venous ends of microcirculation.
• One tenth of the fluid enters the lymphatic capillaries
• High molecular weights like protein cant be reabsorbed into the venous capillaries but thru lymphatic capillaries
Structure of the lymphatic capillaries
• - overlapping endothelial cell provide valve for passage.
Cardiac failure
• -decrease ability of heart to pump blood
• --causes
• --decrease contractility of the heart
• --decrease coronary blood flow
• --damage to the heart valves
• --external pressure
Acute effects of moderate cardiac failure
• --reduced cardiac output
• --damming of blood in the veins- increased in systemic venous pressure
• -from 5 liters/min to less than 2/min
• At <2/min- can sustain life but associated with fainting
• Acute cardiac failure is compensated by sympathetic reflexes
• --baroreceptor reflex
• --chemoreceptor reflex
• --cns ischemic response
• Response
• --strengthens heart contraction
• --increase venous return by increasing vasomotor tone in the veins
• Sympathetic reflex is good for acute phase only
Chronic stage heart failure
• -characterized by
• 1. retention of fluid by the kidneys
• 2. progressive recovery of the heart
• In general renal output remains reduced as long as cardiac output is significantly less than normal
• Beneficial effects of moderate fluid retention in cardiac failure
• --increase tendency for venous return
• ---- increase in mean systemic pressure
• -----distends the veins reduces resistance to venous flow
Decompensated heart failure
• --if severely damaged –cannot be compensated
• --continue to retain fluid – severe edema and eventually lead to death
Sunday, January 13, 2008
BACILLUS
a genus of Gram-positive bacteria
ubiquitous in nature
(soil, water, and airborne dust).
Some species are natural flora in the human intestines.
most species of Bacillus are harmless saprophytes
two species are considered medically significant:
B.anthracis and B. cereus
B. anthracis
causes anthrax in cows, sheep, and sometimes humans.
Anthrax
transmitted to humans via direct contact with animal products
or inhalation of endospores
cells appear to have square ends
• Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis.
• -most commonly occurs in wild and domestic lower vertebrates (cattle, sheep, goats, camels, antelopes, and other herbivores)
• - also occur in humans when they are exposed to infected animals or tissue
• transmitted to humans via direct contact with animal products
• - or inhalation of endospores
CUTANEOUS INFECTION (95% of human cases)
INHALATION ANTHRAX (rare but fatal)
GASTROINTESTINAL ANTHRAX (very rare!)
• Anthrax is most common in agricultural regions where it occurs in animals
it is usually due to an occupational exposure to infected animals or their products
• vaccine is reported to be 93% effective in protecting against anthrax.
Who should be vaccinated
B. cereus
• cause toxin-mediated food poisoning
inhabit many kinds of food including stew, cereal, and milk.
been found in fried rice.
toxins released by the bacterium lead to vomiting and diarrhea, symptoms similar to those of Staphylococcus food poisoning.
proper cold storage of food is recommended immediately after preparation.
LACTOBACILLUS
non-spore-forming bacterium
ferment glucose into lactose, hence the name Lactobacillus.
most common application is industrial-dairy production.
natural flora of the human vagina.
create an acidic environment derive lactic acid from glucose
• Acidic environement inhibits growth of many bacterial species which can lead to
urogenital infections.
generally harmless to humans
• Treatment
- consists of high doses of penicillin in combination with gentamicin.
• promoted as good probiotics for human usage—
Prebiotics ---refers to the soluble fiber component found in certain foods or supplements that stimulate the growth of probiotics in the gastrointestinal tract.
• Lactobacillus Acidophilus
-most commonly used probiotic
Such healthy bacteria inhabit the
intestines and vagina
• -protect against the entrance and
proliferation of "bad" organisms that
• can cause disease.
• the breakdown of food by L. acidophilus leads to production of
• lactic acid
• hydrogen peroxide
•
• and other byproducts that make the environment hostile for undesired organisms
• L. acidophilus also produces lactase, the enzyme that breaks down milk sugar (lactose) into simple sugars
• Probiotics offer a variety of potential therapeutic uses
-Replacing the "friendly" intestinal bacteria destroyed by antibiotics.
Aiding digestion and suppressing disease-causing bacteria.
-Preventing and treating diarrhea
• uses
• Alleviating symptoms of irritable bowel syndrome and, possibly, inflammatory bowel disease
Preventing and/or reducing the recurrence of vaginal yeast infections, urinary tract infections, and cystitis
Enhancing the immune response - yogurt
• Dietary Sources
The primary dietary sources of L. acidophilus include
• - milk enriched with acidophilus
• - yogurt containing live L. acidophilus cultures, miso, and tempeh.
• Available Forms
L. acidophilus preparations consist of dried or liquid cultures of living bacteria.
These cultures are usually grown in milk but can sometimes be grown in milk-free cultures.
• L. acidophilus is available in the following forms:
• Freeze-dried granules
• Freeze-dried powders
• Freeze-dried capsules
• Liquid L. acidophilus preparations (which must be kept refrigerated)
• How to Take It
• Prevention or treatment of diarrhea: 1 to 2 billion viable cells per day
• Vaginal infections: 8 ounces of yogurt
• Clinical experience also suggests that placing yogurt with live acidophilus cultures directly to the vaginal area
Corynebacterium diphtheriae
• Gram positive
strict aerobe
pleomorphic (e.g. club-shaped)
Diphtheria
• infection
– upper respiratory tract (pharynx)
– pseudomembrane
– chocking
– bacteria do not spread systemically
Diptheria toxin
• spreads
• systemic and fatal injury
Treatment
• anti-toxin
• antibiotic
Immunization against diphtheria
(infant)
• disease vanished in US
– without immunization will return
toxoid (+ pertussis and tetanus) DPT
• neutralizing antibodies
colonization not inhibited
– found in normal flora
Clostridium sp
relatively large, Gram-positive, rod-shaped bacteria.
All species form endospores
strictly fermentative mode of metabolism
will not grow under aerobic conditions
vegetative cells are killed by exposure to O2
spores are able to survive long periods of exposure to air
clostridia are ancient organisms
live in virtually all of the anaerobic habitats of nature
where organic compounds are present
soils, aquatic sediments and the intestinal tracts of animals
Clostridium botulinum
Botulism
Botulin is the poison
canning meat, fish, fruits and veggies
In the US an average of 110 cases of botulism are
reported each year
• food poisoning
– rare
– fatal
• germination of spore
• inadequately sterilized canned food
– home
• not an infection
Botulinum toxin
• binds peripheral nerve receptors
– acetylcholine neurotransmitter
• inhibits nerve impulses
• flaccid paralysis
• death
– respiratory
– cardiac failure
Infection with C. botulinum
• Neonatal botulism
– uncommon
– the predominant form of botulism
– colonization occurs
• no normal flora to compete
• unlike adult
Botulinum toxin
• Bioterrorism
– not an infection
– resembles a chemical attack
Treatment
• anti-toxin
• antibiotic therapy (if infection)
Clostridium difficile
"difficile," because they are difficult
pseudomembranous colitis
endoscopy -big white spots
• After antibiotic use
• intestinal normal flora
– greatly decreased
• colonization occurs
• enterotoxin secreted
• pseudomembanous colitis
Therapy
• discontinuation of initial antibiotic (e.g. ampicillin)
• specific antibiotic therapy (e.g. vancomycin)
Clostridium perfringens
invasive pathogen
huge array of invasins and toxins
causes wound and surgical infections
severe uterine infections
• soil, fecal contamination
• war
• gas gangrene
– swelling of tissues
– gas release
* fermentation products
• wound contamination
gas gangrene
foot rot, or boot rot
the foot and leg swell up due to the gas produced
the gas bubbles out
• It smells really fetid like the putrid smell of rotted meat
Pathogenesis
• tissue degrading enzymes
– lecithinase [" toxin]
– proteolytic enzymes
– saccharolytic enzymes
• destruction of blood vessels
• tissue necrosis
• anaerobic environment created
• organism spreads
Without treatment death
occurs within 2 days
Ø effective antibiotic therapy
Ø debridement
Ø anti-toxin
Ø amputation & death is rare
Clostridium tetani
A severe case of tetanus.
muscles, back and legs are rigid
muscle spasms can break bones
can be fatal (e.g respiratory falure
• Non-invasive
Tetanospasmin
• disseminates systemically
• binds to ganglioside receptors
– inhibitory neurones in CNS
• Blocks release of glycine
– Inhibitory neurotransmitter
• stops nerve impulse to muscles
• spastic paralysis
• severe muscle contractions and spasms
• can be fatal
Vaccination
• infant
• DPT (diptheria, pertussis, tetanus)
• tetanus extremely uncommon in US
• tetanus toxoid
– antigenic
– no exotoxic activity
a genus of Gram-positive bacteria
ubiquitous in nature
(soil, water, and airborne dust).
Some species are natural flora in the human intestines.
most species of Bacillus are harmless saprophytes
two species are considered medically significant:
B.anthracis and B. cereus
B. anthracis
causes anthrax in cows, sheep, and sometimes humans.
Anthrax
transmitted to humans via direct contact with animal products
or inhalation of endospores
cells appear to have square ends
• Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis.
• -most commonly occurs in wild and domestic lower vertebrates (cattle, sheep, goats, camels, antelopes, and other herbivores)
• - also occur in humans when they are exposed to infected animals or tissue
• transmitted to humans via direct contact with animal products
• - or inhalation of endospores
CUTANEOUS INFECTION (95% of human cases)
INHALATION ANTHRAX (rare but fatal)
GASTROINTESTINAL ANTHRAX (very rare!)
• Anthrax is most common in agricultural regions where it occurs in animals
it is usually due to an occupational exposure to infected animals or their products
• vaccine is reported to be 93% effective in protecting against anthrax.
Who should be vaccinated
B. cereus
• cause toxin-mediated food poisoning
inhabit many kinds of food including stew, cereal, and milk.
been found in fried rice.
toxins released by the bacterium lead to vomiting and diarrhea, symptoms similar to those of Staphylococcus food poisoning.
proper cold storage of food is recommended immediately after preparation.
LACTOBACILLUS
non-spore-forming bacterium
ferment glucose into lactose, hence the name Lactobacillus.
most common application is industrial-dairy production.
natural flora of the human vagina.
create an acidic environment derive lactic acid from glucose
• Acidic environement inhibits growth of many bacterial species which can lead to
urogenital infections.
generally harmless to humans
• Treatment
- consists of high doses of penicillin in combination with gentamicin.
• promoted as good probiotics for human usage—
Prebiotics ---refers to the soluble fiber component found in certain foods or supplements that stimulate the growth of probiotics in the gastrointestinal tract.
• Lactobacillus Acidophilus
-most commonly used probiotic
Such healthy bacteria inhabit the
intestines and vagina
• -protect against the entrance and
proliferation of "bad" organisms that
• can cause disease.
• the breakdown of food by L. acidophilus leads to production of
• lactic acid
• hydrogen peroxide
•
• and other byproducts that make the environment hostile for undesired organisms
• L. acidophilus also produces lactase, the enzyme that breaks down milk sugar (lactose) into simple sugars
• Probiotics offer a variety of potential therapeutic uses
-Replacing the "friendly" intestinal bacteria destroyed by antibiotics.
Aiding digestion and suppressing disease-causing bacteria.
-Preventing and treating diarrhea
• uses
• Alleviating symptoms of irritable bowel syndrome and, possibly, inflammatory bowel disease
Preventing and/or reducing the recurrence of vaginal yeast infections, urinary tract infections, and cystitis
Enhancing the immune response - yogurt
• Dietary Sources
The primary dietary sources of L. acidophilus include
• - milk enriched with acidophilus
• - yogurt containing live L. acidophilus cultures, miso, and tempeh.
• Available Forms
L. acidophilus preparations consist of dried or liquid cultures of living bacteria.
These cultures are usually grown in milk but can sometimes be grown in milk-free cultures.
• L. acidophilus is available in the following forms:
• Freeze-dried granules
• Freeze-dried powders
• Freeze-dried capsules
• Liquid L. acidophilus preparations (which must be kept refrigerated)
• How to Take It
• Prevention or treatment of diarrhea: 1 to 2 billion viable cells per day
• Vaginal infections: 8 ounces of yogurt
• Clinical experience also suggests that placing yogurt with live acidophilus cultures directly to the vaginal area
Corynebacterium diphtheriae
• Gram positive
strict aerobe
pleomorphic (e.g. club-shaped)
Diphtheria
• infection
– upper respiratory tract (pharynx)
– pseudomembrane
– chocking
– bacteria do not spread systemically
Diptheria toxin
• spreads
• systemic and fatal injury
Treatment
• anti-toxin
• antibiotic
Immunization against diphtheria
(infant)
• disease vanished in US
– without immunization will return
toxoid (+ pertussis and tetanus) DPT
• neutralizing antibodies
colonization not inhibited
– found in normal flora
Clostridium sp
relatively large, Gram-positive, rod-shaped bacteria.
All species form endospores
strictly fermentative mode of metabolism
will not grow under aerobic conditions
vegetative cells are killed by exposure to O2
spores are able to survive long periods of exposure to air
clostridia are ancient organisms
live in virtually all of the anaerobic habitats of nature
where organic compounds are present
soils, aquatic sediments and the intestinal tracts of animals
Clostridium botulinum
Botulism
Botulin is the poison
canning meat, fish, fruits and veggies
In the US an average of 110 cases of botulism are
reported each year
• food poisoning
– rare
– fatal
• germination of spore
• inadequately sterilized canned food
– home
• not an infection
Botulinum toxin
• binds peripheral nerve receptors
– acetylcholine neurotransmitter
• inhibits nerve impulses
• flaccid paralysis
• death
– respiratory
– cardiac failure
Infection with C. botulinum
• Neonatal botulism
– uncommon
– the predominant form of botulism
– colonization occurs
• no normal flora to compete
• unlike adult
Botulinum toxin
• Bioterrorism
– not an infection
– resembles a chemical attack
Treatment
• anti-toxin
• antibiotic therapy (if infection)
Clostridium difficile
"difficile," because they are difficult
pseudomembranous colitis
endoscopy -big white spots
• After antibiotic use
• intestinal normal flora
– greatly decreased
• colonization occurs
• enterotoxin secreted
• pseudomembanous colitis
Therapy
• discontinuation of initial antibiotic (e.g. ampicillin)
• specific antibiotic therapy (e.g. vancomycin)
Clostridium perfringens
invasive pathogen
huge array of invasins and toxins
causes wound and surgical infections
severe uterine infections
• soil, fecal contamination
• war
• gas gangrene
– swelling of tissues
– gas release
* fermentation products
• wound contamination
gas gangrene
foot rot, or boot rot
the foot and leg swell up due to the gas produced
the gas bubbles out
• It smells really fetid like the putrid smell of rotted meat
Pathogenesis
• tissue degrading enzymes
– lecithinase [" toxin]
– proteolytic enzymes
– saccharolytic enzymes
• destruction of blood vessels
• tissue necrosis
• anaerobic environment created
• organism spreads
Without treatment death
occurs within 2 days
Ø effective antibiotic therapy
Ø debridement
Ø anti-toxin
Ø amputation & death is rare
Clostridium tetani
A severe case of tetanus.
muscles, back and legs are rigid
muscle spasms can break bones
can be fatal (e.g respiratory falure
• Non-invasive
Tetanospasmin
• disseminates systemically
• binds to ganglioside receptors
– inhibitory neurones in CNS
• Blocks release of glycine
– Inhibitory neurotransmitter
• stops nerve impulse to muscles
• spastic paralysis
• severe muscle contractions and spasms
• can be fatal
Vaccination
• infant
• DPT (diptheria, pertussis, tetanus)
• tetanus extremely uncommon in US
• tetanus toxoid
– antigenic
– no exotoxic activity
Saturday, January 12, 2008
lec slides on gen pathology
• Atrophy –
• A decrease in individual cell size due to lower rates of metabolism and decreased protein synthesis.
Causes of atrophy
• (1) Decreased workload
• (2) Loss of innervation
• (3) Diminished blood supply
• (4) Inadequate nutrition
• (5) Loss of endocrine stimulation
• (6) Aging
• Hypertrophy –
• An increase in tissue mass resulting from an increase in cell size rather than cell numbers.
Hypertrophy may be caused by
• (1) Increased functional demand
• (2) Hormonal stimulation
• Hyperplasia –
• Increase in tissue mass due to an increased rate of cell division and cellular proliferation.
•
• Hyperplasia may be physiologic or pathologic.
• (1) Physiologic hyperplasia -as a result of
normal hormonal stimulation
e.g., female breast enlargement during puberty and
pregnancy
• (2) Pathologic hyperplasia is the result of a noxious
stimulus
callous formation on the hands of a manual laborer
or excessive hormonal stimulation
• Pathologic hyperplasia
is probably a step in the development of cancer (neoplasia).
• Thus hyperplastic changes in some tissues may be considered premalignant.
• Metaplasia –
• A reversible change in cell structure from one fully differentiated form to another in response to a noxious stimulus.
• represents an attempt by tissue to replace a susceptible cell type with a more resistant one.
metaplasia
• In smokers -columnar cells cells are replaced by stratified squamous epithelium
• Smokers who quit may regain normal mucous secreting bronchial epithelium.
• Persistent stimulus producing metaplasia -it may induce malignant transformation.
• Thus, like hyperplasia, metaplasia is considered a
pre-malignant change.
• Dysplasia –
• Disordered cellular morphology, organization, and function
– Dysplastic tissues display abnormal variation in overall cell size and shape as well as nuclear structure.
– Dysplasia is strongly implicated as a precursor to cancer.
– Dysplasia is distinguished from cancer by the important fact that dysplastic changes can be reversed if the abnormal stimulus is removed.
CELLULAR INJURY
LIMITS OF ADAPTIVE CAPACITY IS EXCEEDED
CAUSE OF REVERSIBLE CELL INJURY AND CELL DEATH
EXTERNAL GROSS PHYSICAL VIOLENCE
INTERNAL ENDOGENOUS CAUSE
CAUSES OF CELLULAR INJURY
• HYPOXIA
• PHYSICAL AGENTS
• CHEMICAL AGENTS AND DRUGS
• INFECTIOUS AGENTS
• IMMUNOLOGICAL REACTIONS
• GENETIC DERANGEMENTS
• NUTRITIONAL IMBALANCES
HYPOXIA
IMPINGES ON AEROBIC OXIDATIVE RESPIRATION
CAUSES OF HYPOXIA
1. LOSS OF BLOOD SUPPLY (ISCHEMIA)
–MOST COMMON CAUSE
2. INADEQUATE OXYGENATION OF BLOOD
- DUE TO CARDIORESPIRATORY FAILURE
3. LOSS OF OXYGEN CARRYING CAPACITY OF
BLOOD
• DEPENDING ON THE SEVERITY OF HYPOXIA THE CEL MAY
ADAPT
UNDERGO INJURY
DIE
MECHANISMS OF CELL INJURY
• 4 INTRACELLULAR SYSTEMS THAT ARE VULNERABLE TO INJURY
• 1. INTEGRITY OF THE CELL MEMBRANE
• 2. AEROBIC RESPIRATION
• 3. PRODUCTION OF ENZYMES AND STRUCTURAL
PROTEIN
• 4. GENETIC APPARATUS
• Injury at one locus can lead to wide ranging secondary effects…
• Impairment of aerobic respiration—lead to disruption of energy dependent sodium pump--- disrupts cellular ionic and fluid balance
Ischemic and hypoxic injury
• Sequence of events and ultrastructural changes
• Occlusion of coronary artery and examination of the muscle supplied by the artery.
Reversible cell injury
• First point of attack in hypoxia
• Aerobic respiration
• Decrease in production of ATP
• In heart muscle occlusion of 60sec. Resulted in cessation of contraction
Anaerobic glycolysis
• Consequence of decrease ATP
• 1. Increase in lactic acid
• 2. Decrease intracellular ph
• 3. Clumping of nuclear material
Acute cellular swelling
• Earliest and most common manifestation of cellular hypoxia
• Impairment of cellular volume regulation
• Failure of active transport by sodium pump
• Accumulation of sodium intracellularly
• Net gain of solute accompanied by isosmotic gain of water
Detachment of ribosome
• Ribosomes detached from E.R.
• Maybe due to disruption of energy-dependent reaction between ribosome and E.R. membrane
• Blebs start to form
• All changes are still reversible
Irreversible cellular injury
• If hypoxia continues irreversible changes occur
• Vacuolization of mitochondria
• Extensive damage to plasma membrane
• Swelling of lysosomes
• Release of lysosomal enzymes
• Digestion of cellular components
• Cell death
Cell death
• Progressive degradation of cell components
• Leakage of cellular enzymes into ECF
• In cardiac muscle after 30-40mins of hypoxia
• SGOT, LDH, CK– criteria for MI
Mechanisms of irreversible injury
• What is the critical biochemical event responsible for the “point of no return”?
• Duration of hypoxia differs in type of tissue
• liver—1 to 2 hrs
• brain ----2 to 3 mins
Cell systems most vulnerable to injuries that induce necrosis include
1. Cell membranes
2. Aerobic respiration
3. Synthetic apparatus (proteins, enzymes)
4. Genetic apparatus
Four common mechanisms associated with injuries that induce necrosis
1. ATP DEPLETION
2. FREE RADICALS
3. MEMBRANE DAMAGE
4. CALCIUM INFLUX
• caspases
• are a family of proteins that are one of the main executors of the apoptotic process.
• They belong to a group of enzymes known as cysteine proteases and exist within the cell as inactive pro-forms or zymogens
Free radicals and cell injury
• Chemical species that has a single unpaired electron in an outer orbital
• Extremely reactive and unstable
• Reacts with inorganic and organic chemicals—key molecules in membranes
• Initiates autocatalyctic reactions
molecules they react to becomes free
radicals themselves thus propagating damage
FREE RADICALS
• MAYBE INITATED WITHIN CELLS BY
1. radiant energy
2. oxidative reactions within normal
metabolism
3.metabolism by exogenous chemicals
The Role of Oxygen-derived Free Radicals
• While oxygen is vital for normal energy metabolism, it also plays a special role in cell injury.
• mitochondria generates
Superoxide
hydrogen peroxide
hydroxyl radicals
• These are short-lived molecules unstable and highly reactive.
MORPHOLOGIC TYPES OF NECROSIS
1. COAGULATION NECROSIS
2. LIQUEFACTION NECROSIS
3. FAT NECROSIS
4. CASEOUS NECROSIS
5. GANGRENOUS NECROSIS
COAGULATION NECROSIS
• most common pattern of necrosis
• lost of nucleus
• preservation of basic cell outline and architecture
• sudden severe ischemia
• denaturation of protein and enzymes
LIQUEFACTION NECROSIS
• Ischemic destruction of brain tissue
• Autolysis and heterolysis by hydrolytic enzymes
• Necrotic tissue is converted to cystic structure
• Filled with fluid and debris
FAT NECROSIS
• Opaque, chalky white deposits
• Fatty acids forming complex with calcium
• Lipases catalyze decomposition of triglycerides
• Acute pancreatic necrosis
CASEOUS NECROSIS
• Combination of coagulative and liquefactive necrosis
• Tuberculous infections
• Friable whitish-gray debris– cheesy material
• Encountered within granulomatous wall
GANGRENOUS NECROSIS
• Usually applied to a limb
• Lost of blood supply in lower limb
• Ischemic cell death and coagulative necrosis modified by liquifactive necrosis
• Dry gangrene – if coagulative predominates
• Wet gangrene – if liquefaction predominates
Chemical injury
• 1. Act directly by combining with some molecular
component or organelle
• 2. Some are converted to reactive toxic
metabolite
May result to
1. membrane injury or
2. generation of free radical
Virus induced cell injury
• 2 types
• 1. cytolytic/cytopathic viruses
• 2. oncogenic tumors
CYTOPATHIC EFFECTS OF VIRUSES
• 1. Rapidly replicating virus particles interfere with host cell metabolism
• 2. Induction of immunologic response
- destruction of cell by antibody or cell mediated reaction
Hepatitis B
• Damage to the hepatocytes
- caused by cytolysis mediated by T lymphocytes
INFLAMMATION
• Inflammation is the process in which healthy tissue responds to an injury
• Purpose of inflammation
1. To destroy and remove substances recognized as being foreign to the body
2. to prevent minor infections from becoming overwhelming
3. To prepare any damaged tissue for repair
INFLAMMATION AND REPAIR
• Reaction of vascularized living tissue to injury
• Destroy, dilute wall off injurious agents
• Heal and repair damaged tissue:
• 1. Regeneration of native parenchymal cell
• 2. filling of defects with fibroblastic tissue(scar)
Causes of Inflammation
• Infection
• Physical trauma
• Chemical trauma
• Irradiation
• Thermal injury (hot or cold)
• Immunity (hypersensitivity)
• Ischemia
• Nutrient deprivation
Acute/Chronic Inflammation
• Short term inflammatory process that complete resolves
– mostly PMN’s
• Chronic Inflammation
long term that may or may not completely
resolve
inflammation
• Acute
-short duration
- exudation of fluid and plasma protein
- emigration of leukocytes
Chronic inflammation
• Longer duration
• Presence of lymphocytes and macrophages
• Proliferation of blood vessels and connective tissue
Systemic Manifestations
• Fever
– endogenous pyrogens are produced by the macrophages and possibly by the eosinophils
• Mechanism
– act on hypothalamus to reset thermostat
– body generates arachidonic acid
– vasoconstriction
– piloerection
– shivering
Changes in vascular flow
• 1.transient vasoconstriction
• 2. vasodilatation – increase blood flow
• 3. slowing of circulation – brought about by
increased in permeability resulting in
hemoconcentration – stasis
• 4. leukocytic margination - emigration
Changes in vascular compartment
• Increase in hydrostatic pressure and vasodilatation - transudation
Cellular events
• Most important feature of inflammation
– -accumulation of leukocytes
– Engulf and degrade bacteria, immune complexes
Margination
Adhesion
Emigration toward chemotactic stimulus
phagocytosis
Systemic Manifestations
• Lymphadenopathy
– enlarged lymph node
• Lymphangiitis
– inflammation of lymphatic vessel
• Lymphadenitis
– inflammation of lymph nodes
Vascular Response
• Momentary vasoconstriction which decreases blood flow
• Vasodilation of the arterioles and venules which increases blood flow
– fluid flows from the capillaries into the interstitial spaces to dilute the injurious agent
– fluid brings complement and antibodies to the area
Cellular Response
• Polymorphonuclear Neutrophils
– first to arrive at the injury
– secrete powerful chemotactic chemicals
Cellular ResponseMargination
• Movement of neutrophils toward the endothelial lining
• Causes of margination
– electrical charge on the endothelial cells changes
– blood viscosity increases
– blood flow slows
– chemical mediators
Cellular Response Diapedesis
• When activated, neutrophils squeeze through the endothelial gaps into the tissues by a process known as Diapedesis
• Diapedesis means “cell-walking
Cellular ResponseChemotaxis
• Chemotaxis
• --is the directional and purposeful movement of cells by ameboid movement toward an area of injury in response to a chemical mediator.
Cellular ResponsePhagocytosis
• The plasma membrane of the neutrophil flows around the foreign particle and engulfs it.
• Lysosomes release chemicals which digest the foreign particle.
• The phagocyte often dies.Cellular debris is removed by monocytes and macrophages
• A decrease in individual cell size due to lower rates of metabolism and decreased protein synthesis.
Causes of atrophy
• (1) Decreased workload
• (2) Loss of innervation
• (3) Diminished blood supply
• (4) Inadequate nutrition
• (5) Loss of endocrine stimulation
• (6) Aging
• Hypertrophy –
• An increase in tissue mass resulting from an increase in cell size rather than cell numbers.
Hypertrophy may be caused by
• (1) Increased functional demand
• (2) Hormonal stimulation
• Hyperplasia –
• Increase in tissue mass due to an increased rate of cell division and cellular proliferation.
•
• Hyperplasia may be physiologic or pathologic.
• (1) Physiologic hyperplasia -as a result of
normal hormonal stimulation
e.g., female breast enlargement during puberty and
pregnancy
• (2) Pathologic hyperplasia is the result of a noxious
stimulus
callous formation on the hands of a manual laborer
or excessive hormonal stimulation
• Pathologic hyperplasia
is probably a step in the development of cancer (neoplasia).
• Thus hyperplastic changes in some tissues may be considered premalignant.
• Metaplasia –
• A reversible change in cell structure from one fully differentiated form to another in response to a noxious stimulus.
• represents an attempt by tissue to replace a susceptible cell type with a more resistant one.
metaplasia
• In smokers -columnar cells cells are replaced by stratified squamous epithelium
• Smokers who quit may regain normal mucous secreting bronchial epithelium.
• Persistent stimulus producing metaplasia -it may induce malignant transformation.
• Thus, like hyperplasia, metaplasia is considered a
pre-malignant change.
• Dysplasia –
• Disordered cellular morphology, organization, and function
– Dysplastic tissues display abnormal variation in overall cell size and shape as well as nuclear structure.
– Dysplasia is strongly implicated as a precursor to cancer.
– Dysplasia is distinguished from cancer by the important fact that dysplastic changes can be reversed if the abnormal stimulus is removed.
CELLULAR INJURY
LIMITS OF ADAPTIVE CAPACITY IS EXCEEDED
CAUSE OF REVERSIBLE CELL INJURY AND CELL DEATH
EXTERNAL GROSS PHYSICAL VIOLENCE
INTERNAL ENDOGENOUS CAUSE
CAUSES OF CELLULAR INJURY
• HYPOXIA
• PHYSICAL AGENTS
• CHEMICAL AGENTS AND DRUGS
• INFECTIOUS AGENTS
• IMMUNOLOGICAL REACTIONS
• GENETIC DERANGEMENTS
• NUTRITIONAL IMBALANCES
HYPOXIA
IMPINGES ON AEROBIC OXIDATIVE RESPIRATION
CAUSES OF HYPOXIA
1. LOSS OF BLOOD SUPPLY (ISCHEMIA)
–MOST COMMON CAUSE
2. INADEQUATE OXYGENATION OF BLOOD
- DUE TO CARDIORESPIRATORY FAILURE
3. LOSS OF OXYGEN CARRYING CAPACITY OF
BLOOD
• DEPENDING ON THE SEVERITY OF HYPOXIA THE CEL MAY
ADAPT
UNDERGO INJURY
DIE
MECHANISMS OF CELL INJURY
• 4 INTRACELLULAR SYSTEMS THAT ARE VULNERABLE TO INJURY
• 1. INTEGRITY OF THE CELL MEMBRANE
• 2. AEROBIC RESPIRATION
• 3. PRODUCTION OF ENZYMES AND STRUCTURAL
PROTEIN
• 4. GENETIC APPARATUS
• Injury at one locus can lead to wide ranging secondary effects…
• Impairment of aerobic respiration—lead to disruption of energy dependent sodium pump--- disrupts cellular ionic and fluid balance
Ischemic and hypoxic injury
• Sequence of events and ultrastructural changes
• Occlusion of coronary artery and examination of the muscle supplied by the artery.
Reversible cell injury
• First point of attack in hypoxia
• Aerobic respiration
• Decrease in production of ATP
• In heart muscle occlusion of 60sec. Resulted in cessation of contraction
Anaerobic glycolysis
• Consequence of decrease ATP
• 1. Increase in lactic acid
• 2. Decrease intracellular ph
• 3. Clumping of nuclear material
Acute cellular swelling
• Earliest and most common manifestation of cellular hypoxia
• Impairment of cellular volume regulation
• Failure of active transport by sodium pump
• Accumulation of sodium intracellularly
• Net gain of solute accompanied by isosmotic gain of water
Detachment of ribosome
• Ribosomes detached from E.R.
• Maybe due to disruption of energy-dependent reaction between ribosome and E.R. membrane
• Blebs start to form
• All changes are still reversible
Irreversible cellular injury
• If hypoxia continues irreversible changes occur
• Vacuolization of mitochondria
• Extensive damage to plasma membrane
• Swelling of lysosomes
• Release of lysosomal enzymes
• Digestion of cellular components
• Cell death
Cell death
• Progressive degradation of cell components
• Leakage of cellular enzymes into ECF
• In cardiac muscle after 30-40mins of hypoxia
• SGOT, LDH, CK– criteria for MI
Mechanisms of irreversible injury
• What is the critical biochemical event responsible for the “point of no return”?
• Duration of hypoxia differs in type of tissue
• liver—1 to 2 hrs
• brain ----2 to 3 mins
Cell systems most vulnerable to injuries that induce necrosis include
1. Cell membranes
2. Aerobic respiration
3. Synthetic apparatus (proteins, enzymes)
4. Genetic apparatus
Four common mechanisms associated with injuries that induce necrosis
1. ATP DEPLETION
2. FREE RADICALS
3. MEMBRANE DAMAGE
4. CALCIUM INFLUX
• caspases
• are a family of proteins that are one of the main executors of the apoptotic process.
• They belong to a group of enzymes known as cysteine proteases and exist within the cell as inactive pro-forms or zymogens
Free radicals and cell injury
• Chemical species that has a single unpaired electron in an outer orbital
• Extremely reactive and unstable
• Reacts with inorganic and organic chemicals—key molecules in membranes
• Initiates autocatalyctic reactions
molecules they react to becomes free
radicals themselves thus propagating damage
FREE RADICALS
• MAYBE INITATED WITHIN CELLS BY
1. radiant energy
2. oxidative reactions within normal
metabolism
3.metabolism by exogenous chemicals
The Role of Oxygen-derived Free Radicals
• While oxygen is vital for normal energy metabolism, it also plays a special role in cell injury.
• mitochondria generates
Superoxide
hydrogen peroxide
hydroxyl radicals
• These are short-lived molecules unstable and highly reactive.
MORPHOLOGIC TYPES OF NECROSIS
1. COAGULATION NECROSIS
2. LIQUEFACTION NECROSIS
3. FAT NECROSIS
4. CASEOUS NECROSIS
5. GANGRENOUS NECROSIS
COAGULATION NECROSIS
• most common pattern of necrosis
• lost of nucleus
• preservation of basic cell outline and architecture
• sudden severe ischemia
• denaturation of protein and enzymes
LIQUEFACTION NECROSIS
• Ischemic destruction of brain tissue
• Autolysis and heterolysis by hydrolytic enzymes
• Necrotic tissue is converted to cystic structure
• Filled with fluid and debris
FAT NECROSIS
• Opaque, chalky white deposits
• Fatty acids forming complex with calcium
• Lipases catalyze decomposition of triglycerides
• Acute pancreatic necrosis
CASEOUS NECROSIS
• Combination of coagulative and liquefactive necrosis
• Tuberculous infections
• Friable whitish-gray debris– cheesy material
• Encountered within granulomatous wall
GANGRENOUS NECROSIS
• Usually applied to a limb
• Lost of blood supply in lower limb
• Ischemic cell death and coagulative necrosis modified by liquifactive necrosis
• Dry gangrene – if coagulative predominates
• Wet gangrene – if liquefaction predominates
Chemical injury
• 1. Act directly by combining with some molecular
component or organelle
• 2. Some are converted to reactive toxic
metabolite
May result to
1. membrane injury or
2. generation of free radical
Virus induced cell injury
• 2 types
• 1. cytolytic/cytopathic viruses
• 2. oncogenic tumors
CYTOPATHIC EFFECTS OF VIRUSES
• 1. Rapidly replicating virus particles interfere with host cell metabolism
• 2. Induction of immunologic response
- destruction of cell by antibody or cell mediated reaction
Hepatitis B
• Damage to the hepatocytes
- caused by cytolysis mediated by T lymphocytes
INFLAMMATION
• Inflammation is the process in which healthy tissue responds to an injury
• Purpose of inflammation
1. To destroy and remove substances recognized as being foreign to the body
2. to prevent minor infections from becoming overwhelming
3. To prepare any damaged tissue for repair
INFLAMMATION AND REPAIR
• Reaction of vascularized living tissue to injury
• Destroy, dilute wall off injurious agents
• Heal and repair damaged tissue:
• 1. Regeneration of native parenchymal cell
• 2. filling of defects with fibroblastic tissue(scar)
Causes of Inflammation
• Infection
• Physical trauma
• Chemical trauma
• Irradiation
• Thermal injury (hot or cold)
• Immunity (hypersensitivity)
• Ischemia
• Nutrient deprivation
Acute/Chronic Inflammation
• Short term inflammatory process that complete resolves
– mostly PMN’s
• Chronic Inflammation
long term that may or may not completely
resolve
inflammation
• Acute
-short duration
- exudation of fluid and plasma protein
- emigration of leukocytes
Chronic inflammation
• Longer duration
• Presence of lymphocytes and macrophages
• Proliferation of blood vessels and connective tissue
Systemic Manifestations
• Fever
– endogenous pyrogens are produced by the macrophages and possibly by the eosinophils
• Mechanism
– act on hypothalamus to reset thermostat
– body generates arachidonic acid
– vasoconstriction
– piloerection
– shivering
Changes in vascular flow
• 1.transient vasoconstriction
• 2. vasodilatation – increase blood flow
• 3. slowing of circulation – brought about by
increased in permeability resulting in
hemoconcentration – stasis
• 4. leukocytic margination - emigration
Changes in vascular compartment
• Increase in hydrostatic pressure and vasodilatation - transudation
Cellular events
• Most important feature of inflammation
– -accumulation of leukocytes
– Engulf and degrade bacteria, immune complexes
Margination
Adhesion
Emigration toward chemotactic stimulus
phagocytosis
Systemic Manifestations
• Lymphadenopathy
– enlarged lymph node
• Lymphangiitis
– inflammation of lymphatic vessel
• Lymphadenitis
– inflammation of lymph nodes
Vascular Response
• Momentary vasoconstriction which decreases blood flow
• Vasodilation of the arterioles and venules which increases blood flow
– fluid flows from the capillaries into the interstitial spaces to dilute the injurious agent
– fluid brings complement and antibodies to the area
Cellular Response
• Polymorphonuclear Neutrophils
– first to arrive at the injury
– secrete powerful chemotactic chemicals
Cellular ResponseMargination
• Movement of neutrophils toward the endothelial lining
• Causes of margination
– electrical charge on the endothelial cells changes
– blood viscosity increases
– blood flow slows
– chemical mediators
Cellular Response Diapedesis
• When activated, neutrophils squeeze through the endothelial gaps into the tissues by a process known as Diapedesis
• Diapedesis means “cell-walking
Cellular ResponseChemotaxis
• Chemotaxis
• --is the directional and purposeful movement of cells by ameboid movement toward an area of injury in response to a chemical mediator.
Cellular ResponsePhagocytosis
• The plasma membrane of the neutrophil flows around the foreign particle and engulfs it.
• Lysosomes release chemicals which digest the foreign particle.
• The phagocyte often dies.Cellular debris is removed by monocytes and macrophages
lec slides on common viral infection
Common viral infections
• Measles
• Rubella
• Mumps
• Varicella or chicken pox
• Influenza
• Hepatitis
• Epstein barr virus or glandular fever
• Cytomegalic virus
• Parvo virus
measles
• Etiologic agent- paramyxovirus
-a common viral infection usually affecting children
-very contagious and is spread by infected people coughing out droplets infected with the virus
characterised by a skin rash or exanthem
-begins with a 4 day prodromal period
consisting of high fever
bright red conjunctivitis
a harsh cough and coryza
development of a maculopapular eruption
maculopapular lesions
starts behind the ears and spreads onto the face, arms, trunk and arms
It becomes confluent and fades by desquamation and staining.
• Koplik spot
• Pathognomonic
of measles
• It is usually an uneventful illness
--but may be complicated by
-viral pneumonia
- secondary bacterial infections
rubella
• caused by the rubella virus
• mild infection of little consequence unless contracted during pregnancy.
• characterised by
– Malaise
– headaches
– conjunctivitis
– and fever
• On the second day a rash of rose-pink or macular spots appears
then fades within 1 to 3 days.
There is accompanying lymphadenopathy
Mumps
• Etiologic agent- paramyxovirus
• usually contracted in childhood
• may be asymptomatic
• or associated with only fever and malaise
It is characteristically associated with
• parotitis
• pancreatitis
• oophoritis
• orchitis
• and lymphocytic meningitis.
Varicella or chicken pox
Etiologic agent --varicella-zoster virus
-infection usually contracted in childhood
initial or primary infection is characterised by
- fever and an eruption
• prodromal period of 1 to 2 days consisting of
– Malaise
– fever
– and vomiting which is followed by the appearance of an eruption
This begins as a macule which rapidly progresses through papule, vesicle, pustule and crust within 48
– Complications in childhood are rare and consist of secondary bacterial infections
– Varicella then becomes a latent viral infection and reactivation may occur 40 to 50 years later as
– -- varicella zoster or shingles
varicella zoster or shingles
• manifests itself usually by recurrence in
• skin
• motor nerves
characterised by the onset of
• severe pain
• hyperaesthesia
• malaise and slight fever
After 3 to 4 days the area affected develops an erythematous rash which is followed by the appearance of closely grouped vesicles. These vesicles rapidly progress to pustules and crusts.
• After 3 to 4 days the area affected develops an
• erythematous rash
• closely grouped vesicles
• pustules and crusts.
Influenza
• Caused by orthomyxoviruses
There are three types of influenza, A, B and C
Type C infuenza - relatively uncommon
type B - produces endemic and small epidemics of influenza
type A virus - produces endemic, epidemic and pandemics of influenza
Influenza
• characterised by
• sudden onset of fever, headaches, myalgia and a cough.
fever usually settles by the third day and the illness by about one week.
The illness may be complicated by a viral or secondary bacterial pneumonia.
VIRAL HEPATITIS
• caused by agents whose primary tissue tropism is the liver.
at least five hepatitis viruses have been recognised, and these have been named:-
Hepatitis A, B, C, D and E.
Clinical Features
• majority of infections are totally asymptomatic
common clinical features include: anorexia, nausea, vomiting, right upper quadrant pain and raised liver enzymes
• Jaundice is the hall mark of infection, but tends to develop late.
Anicteric cases are also very common.
• ENTERICALLY TRANSMITTED HEPATITIS: A and E
PARENTERALLY TRANSMITTED HEPATITIS B , C , D and G
• Hepatitis A - "Infectious Hepatitis"
Caused by a picornavirus, Enterovirus 72
Clinical Features
Incubation period 3-5 weeks (mean 28 days)
-Milder disease than Hepatitis B
-asymptomatic infections are very common, there is no chronic form of the disease.
• Complications:
• Fulminant hepatitis is rare: 0.1% of cases
Pathogenesis
Virus enters via the gut; replicates in the alimentary tract and spreads to infect the liver, where it multiplies in hepatocytes.
Viraemia is transient. Virus is excreted in the stools for two weeks preceding the onset of symptoms.
• Transmission - Enteric
Contamination of food or water with sewage
– Infected food handlers
– Shell fish grown in sewage-polluted water
• Diagnosis
diagnosis is made on the presence of HAV-specific IgM in the patient's blood.
• Prevention
1) Passive immunisation -
Travellers to third world countries
– Household contacts of acute cases
2) Active Immunization
Inactivated cell culture-derived vaccine has recently become available; not in general use
Hepatitis E
• Calicivirus
Recently identified cause of enterically transmitted non-A, non-B (NANB) hepatitis
Clinical Features
Incubation period 30-40 days
Acute, self limiting hepatitis, no chronic carrier state
Age: predominantly young adults, 15-40 years
• Complications
• Fulminant hepatitis in pregnant women. Mortality rate is high (up to 40%).
• Pathogenesis
Similar to hepatitis A
• Diagnosis
No routine laboratory tests are available as yet
Hepatitis B
• Clinical Features
• Incubation period 2 - 5 months
• Insidious onset of symptoms. Tends to cause a more severe disease than Hepatitis A.
• Asymptomatic infections occur frequently.
Pathogenesis
• Infection is parenterally transmitted
The virus replicates in the liver and virus particles, as well as excess viral surface protein, are shed in large amounts into the blood.
Viraemia is prolonged and the blood of infected individuals is highly infectious.
• Complications
• 1) Persistant infection:-
• 5% of infected individuals fail to eliminate the virus completely and become persistantly infected
• The virus persists in the hepatocytes and on-going liver damage occurs because of the host immune response against the infected liver cells
Chronic infection
• Chronic persistent Hepatitis - the virus persists, but there is minimal liver damage
Chronic Active Hepatitis - There is aggressive destruction of liver tissue and rapid progression to cirrhosis or liver failure
• 2) Patients who become persistently infected are at risk of developing hepatocellular carcinoma (HCC)
• 3) Fulminant Hepatitis
• Rare; accounts for 1% of infections.
• Hepatitis B is parenterally transmitted
1) Blood:
• Blood transfusions, serum products,
• sharing of needles, razors
• Tattooing, acupuncture
• Renal dialysis
• Organ donation
2) Sexual intercourse
3) Horizontal transmission in children, families, 'close personal contact'.
.4) Vertical transmission –
perinatal transmission from a carrier mother to her baby
Diagnosis: Serology
A. Acute infection with resolution
Viral antigens
• 1) Surface antigen (HBsAg) - presence in serum indicates that virus replication is occurring in the liver
• 2) 'e' antigen (HBeAg) - Its presence in serum indicates that a high level of viral replication is occurring in the liver
• 3) core antigen (HBcAg) core protein is not found in blood
Antibody response
1) Surface antibody (anti-HBs) –
- indicates immunity following infection-
- It remains detectable for life and is not found in chronic carriers (see below).
2) e antibody (anti-HBe)
-It indicates low infectivity in a carrier.
3) Core IgM rises early in infection and indicates recent infection
4) Core IgG rises soon after IgM, and remains present for life in both chronic carriers as well as those who clear the infection.
• Prevention
• 1) Active Immunization
• Two types of vaccine are available:
– Serum derived - prepared from HBsAg purified from the serum of HBV carriers
– Recombinant HBsAg - made by genetic engineering in yeasts
• Vaccine should be administered to people at high risk of infection with HBV:
– 1) Health care workers
– 2) Sexual partners of chronic carriers
– 3) Infants of HBV carrier mothers
• 2) Passive Antibody
• Hepatitis B immune globulin should be administered to non immune individuals following single episode exposure to HBV-infected blood.
For example: needlestick injuries
Hepatitis C
• The major cause of parenterally transmitted non A non B hepatitis
In 1989, the genome was cloned from the serum of an infected chimpanzee.
Togavirus
Clinical Features
• Incubation period 6-8 weeks
Causes a milder form of acute hepatitis than does hepatitis B
• But 50% individuals develop chronic infection, following exposure
• Complications
• 1) Chronic liver disease
2) Hepatocellular carcinoma
Transmission
• Blood transfusions, blood products
• organ donation
• Intravenous drug abusers
• community acquired: mechanism unclear. ?Vertical transmission
• ?sexual intercourse
Diagnosis
• 1) Serology
Reliable serological tests have only recently become available.
HCV-specific IgG indicates exposure, not infectivity
• 2) PCR detects viral genome in patient's serum
Delta Agent
• Defective virus which requires Hepatitis B as a helper virus in order to replicate.
Infection therefore only occurs in patients who are already infected with Hepatitis B.
Clinial Features
• Increased severity of liver disease in Hepatitis B carriers
Hepatitis G
• originally cloned from the serum of a surgeon with non-A, non-B, non-C hepatitis, has been called Hepatitis G virus.
It was implicated as a cause of parenterally transmitted hepatitis, but is no longer believed to be a major agent of liver disease.
On hiv
Treatment
• attempt to bolster the body's ability to fight HIV
• "therapeutic" vaccines+anti-viral therapy
• may improve the body's response to HIV.
• Other treatments boost CD4 count (T-cells), though this approach is not believed to be useful unless it is combined with an antiviral treatment
Tests That Monitor The Immune System
• HIV viral load.
• testing measures the amount of HIV in blood plasma.
• CD4 count
• measures the number of CD4 cells in a blood sample.
• The CD4 count is one indicator of how much damage HIV has caused to the immune system.
• CD8 count
• CD8s are a different subset of T-cells that include suppressor T-cells and "killer" T-cells.
• At this stage, several things can happen
• The new virus ("provirus") can remain inactive for a long time without triggering the reproduction of virus,
• divide into two proviruses- mitosis
•
• or it can start producing new virus
•
• budding off from the T-cell wall-- eventually destroying the T-cell.
• In the process of viral reproduction
•
• the virus destroys increasing numbers of T-cells
•
• leaving the body open to
• opportunistic infections
•
• How HIV Is Spread
• Requirements For Transmission to Occur
•
• 1. HIV must be present
• 2. In sufficient quantity
• 3. And it must get into the bloodstream.
• Where is HIV Found in the Body?
• HIV can be transmitted from an infected person to another through:
• Blood (including menstrual blood)
• Semen
• Vaginal secretions
• Breast milk
• Possibly infectious "bodily fluids"
• Pre-seminal fluid (pre-cum)
•
•
• Non-infectious "bodily fluids"
• Saliva
• Tears
• Sweat
• Feces
• Urine
•
• Activities That Allow HIV Transmission
• there are three primary ways in which this can happen:
• 1. Unprotected sexual contact
• 2. Direct blood contact
• including injection drug needles, blood transfusions, accidents in health care settings or certain blood products
• 3. Mother to baby
• before or during birth, or through breast milk
• Sexual Routes Of Transmission
• Sexual intercourse (vaginal and anal)
•
• Oral sex (mouth-penis, mouth-vagina)
•
• Heterosexual transmission studies
• Sexual intercourse (vaginal and anal)
•
• Oral sex (mouth-penis, mouth-vagina)
•
• Heterosexual transmission studies
• Non-Sexual Routes Of Transmission
• Sharing injection needles
• Needle sticks
• Blood transfusions
• Hemophilia treatments
• pooled blood of many donors
• Other blood products
• Mother to Child
•
• HIV Is NOT Transmitted By
• Insect bites
• Casual contact
• sharing of dishes/foods
• Donating blood
• Swimming pools/bath tubs
• Pets
• Contact with saliva, tears,sweat,urine,feces
• Rape/sexual assault?
• Transmission Through Tattooing, Piercing, Acupuncture, Electrolysis, and Shaving
•
• What is the risk?
•
• Universal precautions
•
• Measles
• Rubella
• Mumps
• Varicella or chicken pox
• Influenza
• Hepatitis
• Epstein barr virus or glandular fever
• Cytomegalic virus
• Parvo virus
measles
• Etiologic agent- paramyxovirus
-a common viral infection usually affecting children
-very contagious and is spread by infected people coughing out droplets infected with the virus
characterised by a skin rash or exanthem
-begins with a 4 day prodromal period
consisting of high fever
bright red conjunctivitis
a harsh cough and coryza
development of a maculopapular eruption
maculopapular lesions
starts behind the ears and spreads onto the face, arms, trunk and arms
It becomes confluent and fades by desquamation and staining.
• Koplik spot
• Pathognomonic
of measles
• It is usually an uneventful illness
--but may be complicated by
-viral pneumonia
- secondary bacterial infections
rubella
• caused by the rubella virus
• mild infection of little consequence unless contracted during pregnancy.
• characterised by
– Malaise
– headaches
– conjunctivitis
– and fever
• On the second day a rash of rose-pink or macular spots appears
then fades within 1 to 3 days.
There is accompanying lymphadenopathy
Mumps
• Etiologic agent- paramyxovirus
• usually contracted in childhood
• may be asymptomatic
• or associated with only fever and malaise
It is characteristically associated with
• parotitis
• pancreatitis
• oophoritis
• orchitis
• and lymphocytic meningitis.
Varicella or chicken pox
Etiologic agent --varicella-zoster virus
-infection usually contracted in childhood
initial or primary infection is characterised by
- fever and an eruption
• prodromal period of 1 to 2 days consisting of
– Malaise
– fever
– and vomiting which is followed by the appearance of an eruption
This begins as a macule which rapidly progresses through papule, vesicle, pustule and crust within 48
– Complications in childhood are rare and consist of secondary bacterial infections
– Varicella then becomes a latent viral infection and reactivation may occur 40 to 50 years later as
– -- varicella zoster or shingles
varicella zoster or shingles
• manifests itself usually by recurrence in
• skin
• motor nerves
characterised by the onset of
• severe pain
• hyperaesthesia
• malaise and slight fever
After 3 to 4 days the area affected develops an erythematous rash which is followed by the appearance of closely grouped vesicles. These vesicles rapidly progress to pustules and crusts.
• After 3 to 4 days the area affected develops an
• erythematous rash
• closely grouped vesicles
• pustules and crusts.
Influenza
• Caused by orthomyxoviruses
There are three types of influenza, A, B and C
Type C infuenza - relatively uncommon
type B - produces endemic and small epidemics of influenza
type A virus - produces endemic, epidemic and pandemics of influenza
Influenza
• characterised by
• sudden onset of fever, headaches, myalgia and a cough.
fever usually settles by the third day and the illness by about one week.
The illness may be complicated by a viral or secondary bacterial pneumonia.
VIRAL HEPATITIS
• caused by agents whose primary tissue tropism is the liver.
at least five hepatitis viruses have been recognised, and these have been named:-
Hepatitis A, B, C, D and E.
Clinical Features
• majority of infections are totally asymptomatic
common clinical features include: anorexia, nausea, vomiting, right upper quadrant pain and raised liver enzymes
• Jaundice is the hall mark of infection, but tends to develop late.
Anicteric cases are also very common.
• ENTERICALLY TRANSMITTED HEPATITIS: A and E
PARENTERALLY TRANSMITTED HEPATITIS B , C , D and G
• Hepatitis A - "Infectious Hepatitis"
Caused by a picornavirus, Enterovirus 72
Clinical Features
Incubation period 3-5 weeks (mean 28 days)
-Milder disease than Hepatitis B
-asymptomatic infections are very common, there is no chronic form of the disease.
• Complications:
• Fulminant hepatitis is rare: 0.1% of cases
Pathogenesis
Virus enters via the gut; replicates in the alimentary tract and spreads to infect the liver, where it multiplies in hepatocytes.
Viraemia is transient. Virus is excreted in the stools for two weeks preceding the onset of symptoms.
• Transmission - Enteric
Contamination of food or water with sewage
– Infected food handlers
– Shell fish grown in sewage-polluted water
• Diagnosis
diagnosis is made on the presence of HAV-specific IgM in the patient's blood.
• Prevention
1) Passive immunisation -
Travellers to third world countries
– Household contacts of acute cases
2) Active Immunization
Inactivated cell culture-derived vaccine has recently become available; not in general use
Hepatitis E
• Calicivirus
Recently identified cause of enterically transmitted non-A, non-B (NANB) hepatitis
Clinical Features
Incubation period 30-40 days
Acute, self limiting hepatitis, no chronic carrier state
Age: predominantly young adults, 15-40 years
• Complications
• Fulminant hepatitis in pregnant women. Mortality rate is high (up to 40%).
• Pathogenesis
Similar to hepatitis A
• Diagnosis
No routine laboratory tests are available as yet
Hepatitis B
• Clinical Features
• Incubation period 2 - 5 months
• Insidious onset of symptoms. Tends to cause a more severe disease than Hepatitis A.
• Asymptomatic infections occur frequently.
Pathogenesis
• Infection is parenterally transmitted
The virus replicates in the liver and virus particles, as well as excess viral surface protein, are shed in large amounts into the blood.
Viraemia is prolonged and the blood of infected individuals is highly infectious.
• Complications
• 1) Persistant infection:-
• 5% of infected individuals fail to eliminate the virus completely and become persistantly infected
• The virus persists in the hepatocytes and on-going liver damage occurs because of the host immune response against the infected liver cells
Chronic infection
• Chronic persistent Hepatitis - the virus persists, but there is minimal liver damage
Chronic Active Hepatitis - There is aggressive destruction of liver tissue and rapid progression to cirrhosis or liver failure
• 2) Patients who become persistently infected are at risk of developing hepatocellular carcinoma (HCC)
• 3) Fulminant Hepatitis
• Rare; accounts for 1% of infections.
• Hepatitis B is parenterally transmitted
1) Blood:
• Blood transfusions, serum products,
• sharing of needles, razors
• Tattooing, acupuncture
• Renal dialysis
• Organ donation
2) Sexual intercourse
3) Horizontal transmission in children, families, 'close personal contact'.
.4) Vertical transmission –
perinatal transmission from a carrier mother to her baby
Diagnosis: Serology
A. Acute infection with resolution
Viral antigens
• 1) Surface antigen (HBsAg) - presence in serum indicates that virus replication is occurring in the liver
• 2) 'e' antigen (HBeAg) - Its presence in serum indicates that a high level of viral replication is occurring in the liver
• 3) core antigen (HBcAg) core protein is not found in blood
Antibody response
1) Surface antibody (anti-HBs) –
- indicates immunity following infection-
- It remains detectable for life and is not found in chronic carriers (see below).
2) e antibody (anti-HBe)
-It indicates low infectivity in a carrier.
3) Core IgM rises early in infection and indicates recent infection
4) Core IgG rises soon after IgM, and remains present for life in both chronic carriers as well as those who clear the infection.
• Prevention
• 1) Active Immunization
• Two types of vaccine are available:
– Serum derived - prepared from HBsAg purified from the serum of HBV carriers
– Recombinant HBsAg - made by genetic engineering in yeasts
• Vaccine should be administered to people at high risk of infection with HBV:
– 1) Health care workers
– 2) Sexual partners of chronic carriers
– 3) Infants of HBV carrier mothers
• 2) Passive Antibody
• Hepatitis B immune globulin should be administered to non immune individuals following single episode exposure to HBV-infected blood.
For example: needlestick injuries
Hepatitis C
• The major cause of parenterally transmitted non A non B hepatitis
In 1989, the genome was cloned from the serum of an infected chimpanzee.
Togavirus
Clinical Features
• Incubation period 6-8 weeks
Causes a milder form of acute hepatitis than does hepatitis B
• But 50% individuals develop chronic infection, following exposure
• Complications
• 1) Chronic liver disease
2) Hepatocellular carcinoma
Transmission
• Blood transfusions, blood products
• organ donation
• Intravenous drug abusers
• community acquired: mechanism unclear. ?Vertical transmission
• ?sexual intercourse
Diagnosis
• 1) Serology
Reliable serological tests have only recently become available.
HCV-specific IgG indicates exposure, not infectivity
• 2) PCR detects viral genome in patient's serum
Delta Agent
• Defective virus which requires Hepatitis B as a helper virus in order to replicate.
Infection therefore only occurs in patients who are already infected with Hepatitis B.
Clinial Features
• Increased severity of liver disease in Hepatitis B carriers
Hepatitis G
• originally cloned from the serum of a surgeon with non-A, non-B, non-C hepatitis, has been called Hepatitis G virus.
It was implicated as a cause of parenterally transmitted hepatitis, but is no longer believed to be a major agent of liver disease.
On hiv
Treatment
• attempt to bolster the body's ability to fight HIV
• "therapeutic" vaccines+anti-viral therapy
• may improve the body's response to HIV.
• Other treatments boost CD4 count (T-cells), though this approach is not believed to be useful unless it is combined with an antiviral treatment
Tests That Monitor The Immune System
• HIV viral load.
• testing measures the amount of HIV in blood plasma.
• CD4 count
• measures the number of CD4 cells in a blood sample.
• The CD4 count is one indicator of how much damage HIV has caused to the immune system.
• CD8 count
• CD8s are a different subset of T-cells that include suppressor T-cells and "killer" T-cells.
• At this stage, several things can happen
• The new virus ("provirus") can remain inactive for a long time without triggering the reproduction of virus,
• divide into two proviruses- mitosis
•
• or it can start producing new virus
•
• budding off from the T-cell wall-- eventually destroying the T-cell.
• In the process of viral reproduction
•
• the virus destroys increasing numbers of T-cells
•
• leaving the body open to
• opportunistic infections
•
• How HIV Is Spread
• Requirements For Transmission to Occur
•
• 1. HIV must be present
• 2. In sufficient quantity
• 3. And it must get into the bloodstream.
• Where is HIV Found in the Body?
• HIV can be transmitted from an infected person to another through:
• Blood (including menstrual blood)
• Semen
• Vaginal secretions
• Breast milk
• Possibly infectious "bodily fluids"
• Pre-seminal fluid (pre-cum)
•
•
• Non-infectious "bodily fluids"
• Saliva
• Tears
• Sweat
• Feces
• Urine
•
• Activities That Allow HIV Transmission
• there are three primary ways in which this can happen:
• 1. Unprotected sexual contact
• 2. Direct blood contact
• including injection drug needles, blood transfusions, accidents in health care settings or certain blood products
• 3. Mother to baby
• before or during birth, or through breast milk
• Sexual Routes Of Transmission
• Sexual intercourse (vaginal and anal)
•
• Oral sex (mouth-penis, mouth-vagina)
•
• Heterosexual transmission studies
• Sexual intercourse (vaginal and anal)
•
• Oral sex (mouth-penis, mouth-vagina)
•
• Heterosexual transmission studies
• Non-Sexual Routes Of Transmission
• Sharing injection needles
• Needle sticks
• Blood transfusions
• Hemophilia treatments
• pooled blood of many donors
• Other blood products
• Mother to Child
•
• HIV Is NOT Transmitted By
• Insect bites
• Casual contact
• sharing of dishes/foods
• Donating blood
• Swimming pools/bath tubs
• Pets
• Contact with saliva, tears,sweat,urine,feces
• Rape/sexual assault?
• Transmission Through Tattooing, Piercing, Acupuncture, Electrolysis, and Shaving
•
• What is the risk?
•
• Universal precautions
•
Wednesday, January 9, 2008
enterobacteriaceae lec slides
• Gram Negative Bacilli:
• Enteric Gm Neg Bacilli:
– Bacteroides fragilis
– Citrobacter diversus
– Enterobacteriaceae
– Escherichia coli
– Klebsiella Pneumoniae
– Proteus mirabilis
– Salmonella typhi
– Serratia
ENTEROBACTERIACEAE,
VIBRIO, CAMPYLOBACTER
AND HELICOBACTER
Enterobacteriacea
• gastrointestinal diseases
– Escherichia coli
– Salmonella
– Shigella
– Yersinia entercolitica
Enterobacteriaceae
• community acquired
• otherwise healthy people
– Klebsiella pneumoniae
* respiratory diseases
* prominent capsule
– urinary tract infection
– fecal contamination
– E. coli
– Proteus
– urease (degrades urea)
– alkaline urine
– gram negative facultative anaerobic rods
– oxidase negative (no cytochrome oxidase)
Feces
• E. coli
– lactose positive
– not usually identified
– lactose positive sp. common, healthy intestine
• Shigella, Salmonella,Yersinia
– lactose negative
– identified
Diarrhea and Dysentery
Escherichia coli
• E. coli and Shigella
– genetically indistinguishable
– many similarities in diseases
1. Enteropathogenic E. coli
destruction of surface microvilli
• fever
• diarrhea
• vomiting
• nausea
• non-bloody stools
2. Enterotoxigenic E. coli
• diarrhea like cholera
• milder
• travellers diarrhea
3.Enteroinvasive E. coli (EIEC )
• Dysentery
- resembles shigellosis
4. Enterohemorrhagic E. coli
• Enterohemorrhagic E. coliVero toxin
– “shiga-like”
• Hemolysins
Meat
• Hemorrhagic
– bloody, copious diarrhea
– few leukocytes
– afebrile
• hemolytic-uremic syndrome
– hemolytic anemia
– thrombocytopenia (low platelets)
– kidney failure
Treatment -gastrointestinal disease
• fluid replacement
• antibiotics
– not used usually unless systemic
– e.g. hemolytic-uremia syndrome
Shigella
• S. flexneri, S. boydii, S. sonnei, S. dysenteriae
– bacillary dysentery
– shigellosis
• bloody feces
• intestinal pain
• pus
Shigellosis
• within 2-3 days
– epithelial cell damage
Salmonella
• 2000 antigenic "types”
• genetically single species
– S. enterica
• disease category
– S. enteritidis
– many serotypes
– S. cholerae-suis
– S. typhi
Salmonellosis
• S. enteritidis
– the common salmonella infection
– poultry, eggs
– no human reservoir
– Gastroenteritis
• nausea
• vomiting
• non-bloody stool
• self-limiting (2 - 5 days)
• uncomplicated cases (the vast majority)
• antibiotic therapy not useful
S. cholerae-suis
• much less common
• septicemia
• antibiotic therapy essential
Typhoid
• enteric fever
• severest salmonella disease
• Salmonella typhi
• rare in US
• epidemics
– third world
– Europe
* historical
Salmonella typhi
• human reservoir
– carrier state common
• contaminated food
• water supply
• poor sanitary conditions
S. typhi
• Vi (capsular) antigen
– protective
Typhoid -Therapy
• Antibiotics
– essential
• Vaccines
– ineffective
Vibrio cholerae
Vibrios
• Gram negative rods
• comma shaped
• facultative anaerobes
• oxidase positive
• simple nutritional requirements
• readily cultivated
Occurrence -cholera
• third world
• US
– uncommon
* traveler
* ingestion of sea-food
Transmission - V. cholerae
Feces--water
– fresh
– Salt-----
– food
Cholera toxin- Choleragen
• B binds to gangliosides
• provides channel for A
• A catalyses ADP-ribosylation
– regulator complex
– activates adenylate cyclase
Cholera -therapy
• massive secretion of ions/water into
gut lumen
• dehydration and death
• therapy
• fluid replacement
• antibiotic therapy
• vaccination
• partially effective
• not generally used
• international travelers
Vibrio parahemolyticus
• raw sea-food
• grows best in high salt
• not common in US
• diarrhea
CAMPYLOBACTER & HELICOBACTER
• Gram negative rods
• curved or spiral
• genetically related
Campylobacter
C. jejuni
• infects the intestinal tract of animals
– cattle and sheep
– major cause of abortions
Transmission
• milk
• meat products
Isolation - Campylobacter
• microaerophilic
• grows best 42oC
Campylobacter - symptoms
• diarrhea
• malaise
• fever
• abdominal pain
• usually self-limiting
• antibiotics occassionally
• bacteremia
– small minority
Helicobacter pylori
• stomach mucosa
• ulcers
Urease
Important in neutralizing stomach acid
Diagnosis -Helicobacter
• Culture
- urease NH4+ CO2
• mucosal endoscopy NH4
• radioactive CO2 breath
after feeding radioactive urea
Therapy -Helicobacter
• Antibiotics
– cures ulcers
Summary statement
• sanitary measures
– protect the water supply
• food/water borne epidemics
– rare US
– common third world
• zoonotic infections
– contaminated animal products
– less well controlled
– common US and elsewhere
Therapy
• severe diarrhea
– fluid replacement essential
• antibiotic therapy sometimes used in local
infection but always in systemic disease
• Enteric Gm Neg Bacilli:
– Bacteroides fragilis
– Citrobacter diversus
– Enterobacteriaceae
– Escherichia coli
– Klebsiella Pneumoniae
– Proteus mirabilis
– Salmonella typhi
– Serratia
ENTEROBACTERIACEAE,
VIBRIO, CAMPYLOBACTER
AND HELICOBACTER
Enterobacteriacea
• gastrointestinal diseases
– Escherichia coli
– Salmonella
– Shigella
– Yersinia entercolitica
Enterobacteriaceae
• community acquired
• otherwise healthy people
– Klebsiella pneumoniae
* respiratory diseases
* prominent capsule
– urinary tract infection
– fecal contamination
– E. coli
– Proteus
– urease (degrades urea)
– alkaline urine
– gram negative facultative anaerobic rods
– oxidase negative (no cytochrome oxidase)
Feces
• E. coli
– lactose positive
– not usually identified
– lactose positive sp. common, healthy intestine
• Shigella, Salmonella,Yersinia
– lactose negative
– identified
Diarrhea and Dysentery
Escherichia coli
• E. coli and Shigella
– genetically indistinguishable
– many similarities in diseases
1. Enteropathogenic E. coli
destruction of surface microvilli
• fever
• diarrhea
• vomiting
• nausea
• non-bloody stools
2. Enterotoxigenic E. coli
• diarrhea like cholera
• milder
• travellers diarrhea
3.Enteroinvasive E. coli (EIEC )
• Dysentery
- resembles shigellosis
4. Enterohemorrhagic E. coli
• Enterohemorrhagic E. coliVero toxin
– “shiga-like”
• Hemolysins
Meat
• Hemorrhagic
– bloody, copious diarrhea
– few leukocytes
– afebrile
• hemolytic-uremic syndrome
– hemolytic anemia
– thrombocytopenia (low platelets)
– kidney failure
Treatment -gastrointestinal disease
• fluid replacement
• antibiotics
– not used usually unless systemic
– e.g. hemolytic-uremia syndrome
Shigella
• S. flexneri, S. boydii, S. sonnei, S. dysenteriae
– bacillary dysentery
– shigellosis
• bloody feces
• intestinal pain
• pus
Shigellosis
• within 2-3 days
– epithelial cell damage
Salmonella
• 2000 antigenic "types”
• genetically single species
– S. enterica
• disease category
– S. enteritidis
– many serotypes
– S. cholerae-suis
– S. typhi
Salmonellosis
• S. enteritidis
– the common salmonella infection
– poultry, eggs
– no human reservoir
– Gastroenteritis
• nausea
• vomiting
• non-bloody stool
• self-limiting (2 - 5 days)
• uncomplicated cases (the vast majority)
• antibiotic therapy not useful
S. cholerae-suis
• much less common
• septicemia
• antibiotic therapy essential
Typhoid
• enteric fever
• severest salmonella disease
• Salmonella typhi
• rare in US
• epidemics
– third world
– Europe
* historical
Salmonella typhi
• human reservoir
– carrier state common
• contaminated food
• water supply
• poor sanitary conditions
S. typhi
• Vi (capsular) antigen
– protective
Typhoid -Therapy
• Antibiotics
– essential
• Vaccines
– ineffective
Vibrio cholerae
Vibrios
• Gram negative rods
• comma shaped
• facultative anaerobes
• oxidase positive
• simple nutritional requirements
• readily cultivated
Occurrence -cholera
• third world
• US
– uncommon
* traveler
* ingestion of sea-food
Transmission - V. cholerae
Feces--water
– fresh
– Salt-----
– food
Cholera toxin- Choleragen
• B binds to gangliosides
• provides channel for A
• A catalyses ADP-ribosylation
– regulator complex
– activates adenylate cyclase
Cholera -therapy
• massive secretion of ions/water into
gut lumen
• dehydration and death
• therapy
• fluid replacement
• antibiotic therapy
• vaccination
• partially effective
• not generally used
• international travelers
Vibrio parahemolyticus
• raw sea-food
• grows best in high salt
• not common in US
• diarrhea
CAMPYLOBACTER & HELICOBACTER
• Gram negative rods
• curved or spiral
• genetically related
Campylobacter
C. jejuni
• infects the intestinal tract of animals
– cattle and sheep
– major cause of abortions
Transmission
• milk
• meat products
Isolation - Campylobacter
• microaerophilic
• grows best 42oC
Campylobacter - symptoms
• diarrhea
• malaise
• fever
• abdominal pain
• usually self-limiting
• antibiotics occassionally
• bacteremia
– small minority
Helicobacter pylori
• stomach mucosa
• ulcers
Urease
Important in neutralizing stomach acid
Diagnosis -Helicobacter
• Culture
- urease NH4+ CO2
• mucosal endoscopy NH4
• radioactive CO2 breath
after feeding radioactive urea
Therapy -Helicobacter
• Antibiotics
– cures ulcers
Summary statement
• sanitary measures
– protect the water supply
• food/water borne epidemics
– rare US
– common third world
• zoonotic infections
– contaminated animal products
– less well controlled
– common US and elsewhere
Therapy
• severe diarrhea
– fluid replacement essential
• antibiotic therapy sometimes used in local
infection but always in systemic disease
Tuesday, January 8, 2008
slides - bone physio
DAILY TURNOVER RATE RATES FOR CALCIUM IN ADULT
nIntake-------------------------------1000mg
nIntestinal absorption-----------------350mg
nSecretion in GI juices----------------250mg
nNet absorption over secretion-------100mg
nLoss in feces-------------------------900mg
nExcretion in urine--------------------100mg
n90% of calcium in the GMF is reabsorbed in proximal tubules, loops of Henle and early distal tubules
n10% is reabsorbed in the late distal tubules and early collecting ducts – selective
INTESTINAL AND URINARY EXCRETION OF PHOSPHATE
nAlmost all dietary phosphate is absorbed into the blood from the gut
nPhosphate is renal threshold substance
nKidneys regulate ECF conc. of phosphate by altering rate of phosphate excretion in accordance with plasma concentration
cholecalciferol(vit. D3)
liver
25-hydroxycholecalceferol
kidney parathyroid
activation
hormone
1,25-dihydroxycholecalciferol
intestinal epithelium
Calcium calcium alkaline
Binding stimulated phosphate
Protein ATPase
intestinal absorption of calcium
plasma calcium ion concentration
inhibitory
VITAMIN D AND ITS ROLE IN CALCIUM AND PHOSPHATE ABSORPTION
nPotent effect on increasing calcium absorption from the intestine
nImportant effect on bone deposition and reabsorption
nInactive substance thus will have to be activated
VITAMIN D AND ITS ROLE IN CALCIUM AND PHOSPHATE ABSORPTION
INTESTINE ;
ABSORPTION
BONE ;
CALCIUM
ABSORPTION
DEPOSITION
CALCIUM IN THE PLASMA AND INTERSTITIAL FLUID
nConcentration is about 2.4 mmol/liter
n3 forms
1. 40% combined with plasma protein
2. 10% diffusable but combine with other
substances in plasma and interstitial fluid
3. 50% diffusable and ionized
nIonized calcium is important in its effects in the
1. heart
2. nervous system
3. bone formation
NON-BONE PHYSIOLOGICAL EFFECTS OF ALTERED CALCIUM AND PHOSPHATE CONCENTRATION IN THE BODY FLUIDS
nChange in phosphate level - no significant immediate effects on the body
nSlight elevation or decrease of calcium ion concentration can cause extreme physiological effects
tetany from hypocalcemia
nNervous system becomes
Increase in neuronal membrane permeability to sodium ions
nEasy initiation of action potential
nTetanic muscle contraction
nSeizzures
nCarpopedal spasm
nBelow normal value of 9.6 to 6mg/dl
hypercalcemia
nNervous system becomes
nReflex activities are sluggish
nDecrease QT interval of the heart
nConstipation
nLack of appetite
nEffects appear when level is 12mg/dl
BONE AND ITS RELATIONS TO EXTRACELLULAR CALCIUM AND PHOSPHATE
nBone is
- 30% matrix
- 70% calcium salt
nOrganic matrix
- 90-95% collagen fibers
- 5-10%ground substance
BONE SALTS
nCrystalline salts deposited in the organic matrix of bone are principally composed of calcium and phosphate known as hydroxyappatite
nBone stregnth depends on
collagen fibers-tensile strength
calcium phospate- compresional strength
PRECIPITATION AND ABSORPTION OF CALCIUM AND PHOSPHATE IN BONE
nInhibitors are present in all tissues of the body to prevent precipitation
- pyrophosphate
nHydroxyapatite crystals fail to precipitate in normal tissues except in bone
MECHANISM OF BONE CALCIFICATION
nOsteoblasts secrete
collagen monomers
ground substance(mainly proteoglycans)
nPolymerization of collagen monomers to collagen fibers – resulting to formation of
osteoid
nEntrapped osteoblasts become
osteocytes
nFew days after osteoid is formed calcium precipitates on the surface of the collagen fibers
nFinal product of precipitation is hydroxyappatite
nSome remains as amorphous form of salts
nDeposition of calcium maybe due to neutralization of the inhibitor pyrophosphate
PRECIPITATION OF CALCIUM IN NONOSEOUS TISSUES UNDER ABNORMAL CONDITIONS
nArteriosclerosis
nMakes arteries bone-like tubes
nMay deposit also in degenerating tissues and blood clots
nDisappearance of inhibitor in the tissues
EXCHANGEABLE CALCIUM
RAPID BUFFERING MECHANISM - balance or equillibrium of bone calcium and ECF calcium
REMODELING OF BONE
nOsteoblasts – deposition of bone
nOsteoclasts - absorption of bone
– large phagocytic multinucleated cells
nMechanism of absorption
- send out villus like projections
- secretions from villi
1. proteolytic enzymes to dissolve matrix
2. acids like lactic and citric acids to cause solution of bone salt
VALUE OF CONTINUAL REMODELING OF BONE
n1. bone adjusts its strength in proportion to the degree of bone stress
n2. Shape of bone can be rearranged for proper support of mechanical forces by deposition and absorption of bone in accordance with stress patterns
n3. New organic matrix is needed as the old matrix degenerates
CONTROL OF THE RATE OF BONE DEPOSITION BY BONE STRESS
ndeposition of bone at points of
compressional stress -piezoelectric effect
nCompression of bone causes a negative electrical potential in compressed areas and positive potential elswhere
nOsteoblastic activity is noted in negative end of the current and usual osteoclastic activity elswhere
REPAIR OF FRACTURE
nFracture activates all osteoblast involved in the the break
nIncrease in new osteoblasts from osteoprogenitor cells
nCallus formation – bulge of osteoblastic tissue
nBlood alkaline phosphate is used as indicator of bone deposition
nIntake-------------------------------1000mg
nIntestinal absorption-----------------350mg
nSecretion in GI juices----------------250mg
nNet absorption over secretion-------100mg
nLoss in feces-------------------------900mg
nExcretion in urine--------------------100mg
n90% of calcium in the GMF is reabsorbed in proximal tubules, loops of Henle and early distal tubules
n10% is reabsorbed in the late distal tubules and early collecting ducts – selective
INTESTINAL AND URINARY EXCRETION OF PHOSPHATE
nAlmost all dietary phosphate is absorbed into the blood from the gut
nPhosphate is renal threshold substance
nKidneys regulate ECF conc. of phosphate by altering rate of phosphate excretion in accordance with plasma concentration
cholecalciferol(vit. D3)
liver
25-hydroxycholecalceferol
kidney parathyroid
activation
hormone
1,25-dihydroxycholecalciferol
intestinal epithelium
Calcium calcium alkaline
Binding stimulated phosphate
Protein ATPase
intestinal absorption of calcium
plasma calcium ion concentration
inhibitory
VITAMIN D AND ITS ROLE IN CALCIUM AND PHOSPHATE ABSORPTION
nPotent effect on increasing calcium absorption from the intestine
nImportant effect on bone deposition and reabsorption
nInactive substance thus will have to be activated
VITAMIN D AND ITS ROLE IN CALCIUM AND PHOSPHATE ABSORPTION
INTESTINE ;
ABSORPTION
BONE ;
CALCIUM
ABSORPTION
DEPOSITION
CALCIUM IN THE PLASMA AND INTERSTITIAL FLUID
nConcentration is about 2.4 mmol/liter
n3 forms
1. 40% combined with plasma protein
2. 10% diffusable but combine with other
substances in plasma and interstitial fluid
3. 50% diffusable and ionized
nIonized calcium is important in its effects in the
1. heart
2. nervous system
3. bone formation
NON-BONE PHYSIOLOGICAL EFFECTS OF ALTERED CALCIUM AND PHOSPHATE CONCENTRATION IN THE BODY FLUIDS
nChange in phosphate level - no significant immediate effects on the body
nSlight elevation or decrease of calcium ion concentration can cause extreme physiological effects
tetany from hypocalcemia
nNervous system becomes
Increase in neuronal membrane permeability to sodium ions
nEasy initiation of action potential
nTetanic muscle contraction
nSeizzures
nCarpopedal spasm
nBelow normal value of 9.6 to 6mg/dl
hypercalcemia
nNervous system becomes
nReflex activities are sluggish
nDecrease QT interval of the heart
nConstipation
nLack of appetite
nEffects appear when level is 12mg/dl
BONE AND ITS RELATIONS TO EXTRACELLULAR CALCIUM AND PHOSPHATE
nBone is
- 30% matrix
- 70% calcium salt
nOrganic matrix
- 90-95% collagen fibers
- 5-10%ground substance
BONE SALTS
nCrystalline salts deposited in the organic matrix of bone are principally composed of calcium and phosphate known as hydroxyappatite
nBone stregnth depends on
collagen fibers-tensile strength
calcium phospate- compresional strength
PRECIPITATION AND ABSORPTION OF CALCIUM AND PHOSPHATE IN BONE
nInhibitors are present in all tissues of the body to prevent precipitation
- pyrophosphate
nHydroxyapatite crystals fail to precipitate in normal tissues except in bone
MECHANISM OF BONE CALCIFICATION
nOsteoblasts secrete
collagen monomers
ground substance(mainly proteoglycans)
nPolymerization of collagen monomers to collagen fibers – resulting to formation of
osteoid
nEntrapped osteoblasts become
osteocytes
nFew days after osteoid is formed calcium precipitates on the surface of the collagen fibers
nFinal product of precipitation is hydroxyappatite
nSome remains as amorphous form of salts
nDeposition of calcium maybe due to neutralization of the inhibitor pyrophosphate
PRECIPITATION OF CALCIUM IN NONOSEOUS TISSUES UNDER ABNORMAL CONDITIONS
nArteriosclerosis
nMakes arteries bone-like tubes
nMay deposit also in degenerating tissues and blood clots
nDisappearance of inhibitor in the tissues
EXCHANGEABLE CALCIUM
RAPID BUFFERING MECHANISM - balance or equillibrium of bone calcium and ECF calcium
REMODELING OF BONE
nOsteoblasts – deposition of bone
nOsteoclasts - absorption of bone
– large phagocytic multinucleated cells
nMechanism of absorption
- send out villus like projections
- secretions from villi
1. proteolytic enzymes to dissolve matrix
2. acids like lactic and citric acids to cause solution of bone salt
VALUE OF CONTINUAL REMODELING OF BONE
n1. bone adjusts its strength in proportion to the degree of bone stress
n2. Shape of bone can be rearranged for proper support of mechanical forces by deposition and absorption of bone in accordance with stress patterns
n3. New organic matrix is needed as the old matrix degenerates
CONTROL OF THE RATE OF BONE DEPOSITION BY BONE STRESS
ndeposition of bone at points of
compressional stress -piezoelectric effect
nCompression of bone causes a negative electrical potential in compressed areas and positive potential elswhere
nOsteoblastic activity is noted in negative end of the current and usual osteoclastic activity elswhere
REPAIR OF FRACTURE
nFracture activates all osteoblast involved in the the break
nIncrease in new osteoblasts from osteoprogenitor cells
nCallus formation – bulge of osteoblastic tissue
nBlood alkaline phosphate is used as indicator of bone deposition
Saturday, January 5, 2008
lecture slides on energectics and body temperature regulation
ENERGETICS AND METABOLIC RATE
Importance of ATP in metabolism
-large quantity of free energy in its high energy phosphate
bonds (7000cal /mol)
Transfer of energy from diff foodstuff to functional system of the cell
Phosphate bonds – release stored energy
PHOSPHOCREATINE
Storage depot for energy
Buffering the concentration of ATP
Most abundant substance that stores energy
Can’t act as ATP but can transfer energy with ATP
-extra amount of ATP synthesis of phosphocreatine
when ATP is used up energy from phosphocreatine
is transferred back to ATP
- concentration of ATP is maintained at high level-
ATP buffer system
ANEROBIC/AEROBIC ENERGY
Anaerobic – energy derived from foods without the
use of O2
Aerobic –energy derived from foods by oxidative
metabolism
Glycogen storage is the only food for anaerobic
metabolism - glycolysis
What happens to Pyruvate
If oxygen is present it is converted to Acetyl-CoA and enters citric acid cycle
If oxygen is not present is will become lactic acid and /or ethanol
Oxidative Respiration
aerobic metabolism
occurs in mitochondria
conversion of pyruvate to Acetyl-CoA
citric acid cycle
electron transport
Anaerobic Metabolism (fermentation) occurs when oxygen is not available.
ethanol fermentation (Yeast)
Pyruvate is converted to acetaldehyde, by removal of CO2. Which then accepts H from NADH to produce ethyl alcohol.
Lactic Acid Fermentation
takes H from NADH and attaches it to pyruvate to produce lactic acid (Muscles)
Oxidative Respiration
aerobic metabolism
occurs in mitochondria
conversion of pyruvate to Acetyl-CoA
citric acid cycle
electron transport
How Cells Make atp
by
PHOSPHORYLATION... adding a phosphate to ADP
ADP + P ------> ATP
) substrate level phosphorylation...
where a substrate molecule ( X-p ) donates its P to ADP making ATP
b) chemiosmosis - [Oxidative Phosphorylation of Krebs cycle & ETC]...
food substrates donate e- & protons to acceptor molecules [NADH], i.e., oxidation.
NADH gives up electrons & protons are pumped out of mitochondria
protons diffuse back into mito thru an enzyme - ATPase,
the ATPase enzyme makes ADP + P --> ATP
Complex I
NADH dehydrogenase (or)
NADH-coenzyme Q reductase
Complex II
Succinate dehydrogenase (or)
Succinate-coenzyme Q reductase
Complex III
Cytochrome C - coenzyme Q oxidoreductase-
Complex IV
Cytochrome oxidase
Complex VATP synthase
ANAEROBIC ENERGY DURING HYPOXIA
Acute hypoxia – O2 in the lungs/hemoglobin is good only
for 2 mins – glycolysis
Anaerobic energy usage during strenuous bursts of activity
-energy is derived from
1. ATP already present in the muscle cells
2. phosphocreatine in the cells
3. anaerobic energy from glycolysis
4. oxidative energy from oxidative process
Max. amount of ATP in a liter of intracellualr fluid – 5 millimoles - can maintain contraction for a second
Phosphocreatine is 3 to 8 times this amount – can
maintain contraction for few more seconds
Energy from glycolysis can occur rapidly than from oxidative
process
Glycogen content of the muscle during exercise is reduced
while lactic acid increases
After exercise – reconversion of lactic acid to glucose
Oxygen debt – rapid breathing after exercise
Excess O2 is used to
1. reconvert lactic acid to glucose
2. reconvert ATP/ phosphocreatine to normal
3. restablished normal conc of O2 in Hg/ myoglobin
4. O2 in the lungs
SUMMARY OF ENERGY UTILIZATION
glycogen energy for
synthesis and growth
Glucose ATP muscular contraction
glandular secretion
Lactic acid pyruvic acid nerve conduction
active absorption
Acetyl-coA
Deaminated a.a. phosphocreatine
Other substrate AMP
CO2 +H2O creatine+phosphate
CONTROL OF ENERGY RELEASE IN THE CELL
1. rate control of enzyme-catalyzed reaction
2. role of enzyme conc. in the regulation of
metabolic reaction
3.role of substrate concentration
4. rate limitation in a series of reaction
5. ADP conc. as rate controlling factor
THE METABOLIC RATE
Metabolism – all chemical reaction in the body
Heat – end product of energy released in the body
35% of energy in the foods becomes heat during ATP
formation
Only 27% of energy from food is utilized by the cell’s
functional system
But all eventually becomes heat
Calorie – unit for expressing the quantity of energy released
from foods or expended by diff. functional process
in the body
MEASUREMENT OF METABOLIC RATE
1. direct calorimetry
-quantity of heat liberated from the body at any
given time(not doing external work)
- uses calorimeter- insulated air chamber
- heat gain by cool water bath
2. indirect calorimetry- oxygen utilization
3. metabolator –floating drum with O2 chamber to a
mouthpiece thru 2 tubes
\
The Formula
B x 10 x A x C = Your Basic Metabolic Rate
FACTORS AFFECTING METABOLIC RATE
1. exercise – most dramatic effect
- may increased to 2000%
2. energy requirements for daily activity
- avg. 70 kg. man lying in bed -1650cal/day
- process of eating and digesting of food- 200cal
- daily requirement for existing – 2000cal/day
3. effects of diff. types of work
4. specific dynamic action of protein
5. age – rate of cellular reaction
6. sympathetic stimulation- increase cellular activity
increase liver muscle glycogenolysis
-non shivering thermogenesis
7. male sex hormones
8. Growth hormones
9. fever
10. climate
11. sleep – decrease muscle tone – sympathetic stimulation
12. malnutrition
BASAL METABOLIC RATE
Rate of energy utilization in the body during absolute rest
but while a person is awake
Conditions for measuring BMR
1. NPO at least 12 hours
2. after a night of restful sleep
3. no strenuous activity preceding 1 hour
4. psychic and physical factors causing excitement be
eliminated
5. temperature of air must be comfortable
METHODS FOR MEASURING BMR
Expressing BMR in terms of surface area
- percentage above or below normal
Constancy of BMR in same person
- person to person
BODY TEMPERATURE: REGULATION AND FEVER
Normal body temperature
-core temperature – deep tissue of the body
-constant
Skin temperature – rises and falls
Body temperature – balance of heat production
and heat loss
Heat production from :
1. BMR of all cells
2. metabolism cause by muscle activity
3. effect of thyroxin
4. sympathetic stimulation
5. increase in temperature
Heat production – generated in deep organs
liver, brain, heart, skeletal muscle
Heat transferred to the skin
Rate of heat loss
1. rate of conduction from core to skin
2. rate of transfer from skin to surrounding tissue
THE INSULATOR SYSTEM OF THE BODY
Skin, subcutaneous tissue and fat - insulator
Fat conducts heat only one third as readily
Effect of blood flow
-venous plexuses below the skin
-arteriovenous anastomosis
-increase rate of blood flow heat loss
Control of heat conduction to the skin is regulated
by sympathetic nervous system
PHYSICS OF HEAT LOSS FROM SKIN
1. radiation – in the form of infrared heat rays
- 60% of heat loss
2. conduction - to objects to air air convection
3 convection – heat loss thru air currents
- cooling effect of wind
-water adjacent to the skin
4. evaporation – when water evaporates from the
body heat is also loss
- insensible heat loss
SWEATING
Its regulation – anterior hypothalamus pre
optic area
Sweat glands – sympathetic cholinergic fibers –
responsive to epinephrine
MECHANISM OF SWEAT SECRETION
Sweat gland – tubular – 2 parts
1. deep subdermal – coiled portion
2. duct portion
Epithelial lining in coiled portion forms the primary or
precursor secretion ( similar to plasma secretion)
Composition is modified by reabsorption of sodium and
potassium
Depends on sympathetic stimulation
Acclimatization of sweat mechanism
Rarely 700cc/hr if not acclimatized
Progressive sweating occurs when exposure to hot temperature is increased
-Maximum of 2 liters/ hr
Decrease sodium chloride loss - 3 – 5 gms/day – due aldosterone
REGULATION OF BODY TEMPERATURE
Anterior hypothalamus preoptic area
– heat /cold sensitive neurons
When stimulated
– profuse sweating and vasodilation
DETECTION OF TEMPERATURE
Receptors from skin and deep tissues
More cold receptors than warm receptors
When skin is chilled – reflex reaction
1. shivering
2. inhibit sweating
3. vasoconstriction
Both receptors are important in prevention of
hypothermia
ROLE OF HYPOTHALAMUS
Integration of peripheral and central
temperature signals
Responsible for providing either heat producing
or heat conserving reaction
TEMPERATURE DECREASING MECHANISM WHEN BODY IS TOO HOT
1. vasodilatation
2. sweating
3. decrease heat production
1. vasodilatation
2. sweating
3. decrease heat production
1. skin vasoconstriction
2. piloerection
3. increase in heat production
-shivering- primary motor center in hypothalamus
- sympathetic excitation of heat production
chemical thermogenesis – uncoupled oxidation
-thyroxine secretion- release of thyrotropin-
releasing hormone—throid stimulating hormone
thyroxin chemical thermogenesis
SET POINT FOR TEMPERATURE CONTROL
Critical core body temperature --- 37.1 degree centigrade
Above or below this temperature –
- change in the rate of heat loss or heat production
by temperature regulating mechanism of the body
Heat temperature receptors in the ant hypothalamic-preop-
-tic area
Can be altered by temperature signals from the peripheral
areas of the body
ABNORMALITIES OF BODY TEMPERATURE REGULATION
Fever – body temperature above normal
- causes: 1. bacterial diseases
2. brain tumors
3. environmental conditions
Resetting of the hypothalamic temperature regulating center
in febrile conditions
Illness- effects of pyrogens(Proteins, breakdown products of
proteins,lipopolysacharride,toxins)
- cause set point to increase
- activates mechanism for increasing body temperature
MECHANISM OF ACTION OF PYROGENS IN CAUSING FEVER
Directly acting on hypothalamic regulating center
Indirect action – bacterial pyrogens(endotoxin)
bacterial phagocytosis by blood cells digestion
release of interleukin1 hypothalamus
One 10,000,000th of a gram
Formation of prostaglandin acts on hypothalamus
fever
Aspirin – blocks formation of prostaglandin
CHARACTERISTICS OF FEVER
Change of set point to higher level
-since blood temperature is lower
- body respond to increase temperature
- chills, cold vasoconstriction
- equalized hypothalamic setting
Crisis or flush
--removal of factor causing fever
--set point returns to normal
--body temperature still high
--heating of hypothalamus from peripheral recptors
--activates temperature regulating mechanism
--sweating
--vasodilatation
The danger of dehydration and heat stroke
can be life-threatening if left untreated.
What is heat stroke?
What is heat stroke?
It is the result of long, extreme exposure to the sun, in which a person does not sweat enough to lower body temperature.
The elderly, infants, persons who work outdoors and those on certain types of medications are most susceptible to heat stroke.
It is a condition that develops rapidly and requires immediate medical treatment.
Limits of heat one can withstand – dry/wet
Limitation of losing heat by heat regulating capacity
Thalamus is also depressed
Body temperature of 106-108OF heat stroke
symptoms -dizziness, abdominal distress, delirium
-loss of consciousness, circulatory shock
Hyperpyrexia – brain damaging
Could be fatal
prevention – ice-water bath – uncontrollable
shivering
- sponge or spray cooling
Harmful effects of high temperature
-local hemorrhages
-parenchymatous degeneration of cells
ACCLIMATIZATION TO HEAT
Increase maximum rate of sweating
Increase plasma volume
Decrease salt loss in sweat and urine
-due to aldosterone
EXPOSURE OF BODY TO EXTREME COLD
30 mins. exposure to ice water
-heart stand-still or fibrillation
Loss of temperature regulation at low temperature
Loss of chemical heat production in the cell
Sleepiness/coma
-depress cns heat control mechanism
-prevents shivering
Hypothermia is defined as a core temperature of less than 35 degrees Celcius.
the clinical state of sub-normal temperature when the body is unable to generate sufficient heat to efficiently maintain functions.
The healthy individual's compensatory responses to heat loss via conduction, convection, radiation, evaporation and respiration may be overwhelmed by exposure.
Once hypothermia develops, the heat deficit is shared by two body compartments, the shell and the core.
Medications may interfere with thermoregulation. Acute or chronic central nervous system processes may decrease the efficiency of thermoregulation
Hypothermia
Warnings signs of Hypothermia are uncontrollable shivering
memory loss
disorientation
incoherence
slurred speech
drowsiness
and apparent exhaustion.
Patients cold, stiff and cyanotic, with fixed pupils and no audible heart tones or visible thoracic excursions have been successfully resuscitated.
The only certain criterion for death in hypothermia is irreversibility of cardiac arrest when the patient is warm.
Conclusions regarding the potential reversibility of coexisting conditions should be withheld until the patient is rewarmed.
Resuscitation, including CPR if necessary, should be continued until either failure after hospital rewarming to 35 degrees Celcius or danger through exposure to rescuers exists.
If medical care is unavailable
start warming the body slowly
warm the body core first
use your own body heat to help
get the victim into dry clothing
and wrap them in a warm blanket covering the head and neck.
Frost bite
-freezing of surface area of the body
-ears, digits of hand/feet
-gangrene
Protection against frost bite – vasodilatation
Artificial hypothermia
-sedation
-depress cns temperature regulating mech.
- ice, cooling blankets
- alcohol
ARTIFICIAL HYPOTHERMIA
Strong sedative-depressing the reactivity of hypothalamic temperature controller
Cooling with ice
Used in heart surgery
Organ transport
Importance of ATP in metabolism
-large quantity of free energy in its high energy phosphate
bonds (7000cal /mol)
Transfer of energy from diff foodstuff to functional system of the cell
Phosphate bonds – release stored energy
PHOSPHOCREATINE
Storage depot for energy
Buffering the concentration of ATP
Most abundant substance that stores energy
Can’t act as ATP but can transfer energy with ATP
-extra amount of ATP synthesis of phosphocreatine
when ATP is used up energy from phosphocreatine
is transferred back to ATP
- concentration of ATP is maintained at high level-
ATP buffer system
ANEROBIC/AEROBIC ENERGY
Anaerobic – energy derived from foods without the
use of O2
Aerobic –energy derived from foods by oxidative
metabolism
Glycogen storage is the only food for anaerobic
metabolism - glycolysis
What happens to Pyruvate
If oxygen is present it is converted to Acetyl-CoA and enters citric acid cycle
If oxygen is not present is will become lactic acid and /or ethanol
Oxidative Respiration
aerobic metabolism
occurs in mitochondria
conversion of pyruvate to Acetyl-CoA
citric acid cycle
electron transport
Anaerobic Metabolism (fermentation) occurs when oxygen is not available.
ethanol fermentation (Yeast)
Pyruvate is converted to acetaldehyde, by removal of CO2. Which then accepts H from NADH to produce ethyl alcohol.
Lactic Acid Fermentation
takes H from NADH and attaches it to pyruvate to produce lactic acid (Muscles)
Oxidative Respiration
aerobic metabolism
occurs in mitochondria
conversion of pyruvate to Acetyl-CoA
citric acid cycle
electron transport
How Cells Make atp
by
PHOSPHORYLATION... adding a phosphate to ADP
ADP + P ------> ATP
) substrate level phosphorylation...
where a substrate molecule ( X-p ) donates its P to ADP making ATP
b) chemiosmosis - [Oxidative Phosphorylation of Krebs cycle & ETC]...
food substrates donate e- & protons to acceptor molecules [NADH], i.e., oxidation.
NADH gives up electrons & protons are pumped out of mitochondria
protons diffuse back into mito thru an enzyme - ATPase,
the ATPase enzyme makes ADP + P --> ATP
Complex I
NADH dehydrogenase (or)
NADH-coenzyme Q reductase
Complex II
Succinate dehydrogenase (or)
Succinate-coenzyme Q reductase
Complex III
Cytochrome C - coenzyme Q oxidoreductase-
Complex IV
Cytochrome oxidase
Complex VATP synthase
ANAEROBIC ENERGY DURING HYPOXIA
Acute hypoxia – O2 in the lungs/hemoglobin is good only
for 2 mins – glycolysis
Anaerobic energy usage during strenuous bursts of activity
-energy is derived from
1. ATP already present in the muscle cells
2. phosphocreatine in the cells
3. anaerobic energy from glycolysis
4. oxidative energy from oxidative process
Max. amount of ATP in a liter of intracellualr fluid – 5 millimoles - can maintain contraction for a second
Phosphocreatine is 3 to 8 times this amount – can
maintain contraction for few more seconds
Energy from glycolysis can occur rapidly than from oxidative
process
Glycogen content of the muscle during exercise is reduced
while lactic acid increases
After exercise – reconversion of lactic acid to glucose
Oxygen debt – rapid breathing after exercise
Excess O2 is used to
1. reconvert lactic acid to glucose
2. reconvert ATP/ phosphocreatine to normal
3. restablished normal conc of O2 in Hg/ myoglobin
4. O2 in the lungs
SUMMARY OF ENERGY UTILIZATION
glycogen energy for
synthesis and growth
Glucose ATP muscular contraction
glandular secretion
Lactic acid pyruvic acid nerve conduction
active absorption
Acetyl-coA
Deaminated a.a. phosphocreatine
Other substrate AMP
CO2 +H2O creatine+phosphate
CONTROL OF ENERGY RELEASE IN THE CELL
1. rate control of enzyme-catalyzed reaction
2. role of enzyme conc. in the regulation of
metabolic reaction
3.role of substrate concentration
4. rate limitation in a series of reaction
5. ADP conc. as rate controlling factor
THE METABOLIC RATE
Metabolism – all chemical reaction in the body
Heat – end product of energy released in the body
35% of energy in the foods becomes heat during ATP
formation
Only 27% of energy from food is utilized by the cell’s
functional system
But all eventually becomes heat
Calorie – unit for expressing the quantity of energy released
from foods or expended by diff. functional process
in the body
MEASUREMENT OF METABOLIC RATE
1. direct calorimetry
-quantity of heat liberated from the body at any
given time(not doing external work)
- uses calorimeter- insulated air chamber
- heat gain by cool water bath
2. indirect calorimetry- oxygen utilization
3. metabolator –floating drum with O2 chamber to a
mouthpiece thru 2 tubes
\
The Formula
B x 10 x A x C = Your Basic Metabolic Rate
FACTORS AFFECTING METABOLIC RATE
1. exercise – most dramatic effect
- may increased to 2000%
2. energy requirements for daily activity
- avg. 70 kg. man lying in bed -1650cal/day
- process of eating and digesting of food- 200cal
- daily requirement for existing – 2000cal/day
3. effects of diff. types of work
4. specific dynamic action of protein
5. age – rate of cellular reaction
6. sympathetic stimulation- increase cellular activity
increase liver muscle glycogenolysis
-non shivering thermogenesis
7. male sex hormones
8. Growth hormones
9. fever
10. climate
11. sleep – decrease muscle tone – sympathetic stimulation
12. malnutrition
BASAL METABOLIC RATE
Rate of energy utilization in the body during absolute rest
but while a person is awake
Conditions for measuring BMR
1. NPO at least 12 hours
2. after a night of restful sleep
3. no strenuous activity preceding 1 hour
4. psychic and physical factors causing excitement be
eliminated
5. temperature of air must be comfortable
METHODS FOR MEASURING BMR
Expressing BMR in terms of surface area
- percentage above or below normal
Constancy of BMR in same person
- person to person
BODY TEMPERATURE: REGULATION AND FEVER
Normal body temperature
-core temperature – deep tissue of the body
-constant
Skin temperature – rises and falls
Body temperature – balance of heat production
and heat loss
Heat production from :
1. BMR of all cells
2. metabolism cause by muscle activity
3. effect of thyroxin
4. sympathetic stimulation
5. increase in temperature
Heat production – generated in deep organs
liver, brain, heart, skeletal muscle
Heat transferred to the skin
Rate of heat loss
1. rate of conduction from core to skin
2. rate of transfer from skin to surrounding tissue
THE INSULATOR SYSTEM OF THE BODY
Skin, subcutaneous tissue and fat - insulator
Fat conducts heat only one third as readily
Effect of blood flow
-venous plexuses below the skin
-arteriovenous anastomosis
-increase rate of blood flow heat loss
Control of heat conduction to the skin is regulated
by sympathetic nervous system
PHYSICS OF HEAT LOSS FROM SKIN
1. radiation – in the form of infrared heat rays
- 60% of heat loss
2. conduction - to objects to air air convection
3 convection – heat loss thru air currents
- cooling effect of wind
-water adjacent to the skin
4. evaporation – when water evaporates from the
body heat is also loss
- insensible heat loss
SWEATING
Its regulation – anterior hypothalamus pre
optic area
Sweat glands – sympathetic cholinergic fibers –
responsive to epinephrine
MECHANISM OF SWEAT SECRETION
Sweat gland – tubular – 2 parts
1. deep subdermal – coiled portion
2. duct portion
Epithelial lining in coiled portion forms the primary or
precursor secretion ( similar to plasma secretion)
Composition is modified by reabsorption of sodium and
potassium
Depends on sympathetic stimulation
Acclimatization of sweat mechanism
Rarely 700cc/hr if not acclimatized
Progressive sweating occurs when exposure to hot temperature is increased
-Maximum of 2 liters/ hr
Decrease sodium chloride loss - 3 – 5 gms/day – due aldosterone
REGULATION OF BODY TEMPERATURE
Anterior hypothalamus preoptic area
– heat /cold sensitive neurons
When stimulated
– profuse sweating and vasodilation
DETECTION OF TEMPERATURE
Receptors from skin and deep tissues
More cold receptors than warm receptors
When skin is chilled – reflex reaction
1. shivering
2. inhibit sweating
3. vasoconstriction
Both receptors are important in prevention of
hypothermia
ROLE OF HYPOTHALAMUS
Integration of peripheral and central
temperature signals
Responsible for providing either heat producing
or heat conserving reaction
TEMPERATURE DECREASING MECHANISM WHEN BODY IS TOO HOT
1. vasodilatation
2. sweating
3. decrease heat production
1. vasodilatation
2. sweating
3. decrease heat production
1. skin vasoconstriction
2. piloerection
3. increase in heat production
-shivering- primary motor center in hypothalamus
- sympathetic excitation of heat production
chemical thermogenesis – uncoupled oxidation
-thyroxine secretion- release of thyrotropin-
releasing hormone—throid stimulating hormone
thyroxin chemical thermogenesis
SET POINT FOR TEMPERATURE CONTROL
Critical core body temperature --- 37.1 degree centigrade
Above or below this temperature –
- change in the rate of heat loss or heat production
by temperature regulating mechanism of the body
Heat temperature receptors in the ant hypothalamic-preop-
-tic area
Can be altered by temperature signals from the peripheral
areas of the body
ABNORMALITIES OF BODY TEMPERATURE REGULATION
Fever – body temperature above normal
- causes: 1. bacterial diseases
2. brain tumors
3. environmental conditions
Resetting of the hypothalamic temperature regulating center
in febrile conditions
Illness- effects of pyrogens(Proteins, breakdown products of
proteins,lipopolysacharride,toxins)
- cause set point to increase
- activates mechanism for increasing body temperature
MECHANISM OF ACTION OF PYROGENS IN CAUSING FEVER
Directly acting on hypothalamic regulating center
Indirect action – bacterial pyrogens(endotoxin)
bacterial phagocytosis by blood cells digestion
release of interleukin1 hypothalamus
One 10,000,000th of a gram
Formation of prostaglandin acts on hypothalamus
fever
Aspirin – blocks formation of prostaglandin
CHARACTERISTICS OF FEVER
Change of set point to higher level
-since blood temperature is lower
- body respond to increase temperature
- chills, cold vasoconstriction
- equalized hypothalamic setting
Crisis or flush
--removal of factor causing fever
--set point returns to normal
--body temperature still high
--heating of hypothalamus from peripheral recptors
--activates temperature regulating mechanism
--sweating
--vasodilatation
The danger of dehydration and heat stroke
can be life-threatening if left untreated.
What is heat stroke?
What is heat stroke?
It is the result of long, extreme exposure to the sun, in which a person does not sweat enough to lower body temperature.
The elderly, infants, persons who work outdoors and those on certain types of medications are most susceptible to heat stroke.
It is a condition that develops rapidly and requires immediate medical treatment.
Limits of heat one can withstand – dry/wet
Limitation of losing heat by heat regulating capacity
Thalamus is also depressed
Body temperature of 106-108OF heat stroke
symptoms -dizziness, abdominal distress, delirium
-loss of consciousness, circulatory shock
Hyperpyrexia – brain damaging
Could be fatal
prevention – ice-water bath – uncontrollable
shivering
- sponge or spray cooling
Harmful effects of high temperature
-local hemorrhages
-parenchymatous degeneration of cells
ACCLIMATIZATION TO HEAT
Increase maximum rate of sweating
Increase plasma volume
Decrease salt loss in sweat and urine
-due to aldosterone
EXPOSURE OF BODY TO EXTREME COLD
30 mins. exposure to ice water
-heart stand-still or fibrillation
Loss of temperature regulation at low temperature
Loss of chemical heat production in the cell
Sleepiness/coma
-depress cns heat control mechanism
-prevents shivering
Hypothermia is defined as a core temperature of less than 35 degrees Celcius.
the clinical state of sub-normal temperature when the body is unable to generate sufficient heat to efficiently maintain functions.
The healthy individual's compensatory responses to heat loss via conduction, convection, radiation, evaporation and respiration may be overwhelmed by exposure.
Once hypothermia develops, the heat deficit is shared by two body compartments, the shell and the core.
Medications may interfere with thermoregulation. Acute or chronic central nervous system processes may decrease the efficiency of thermoregulation
Hypothermia
Warnings signs of Hypothermia are uncontrollable shivering
memory loss
disorientation
incoherence
slurred speech
drowsiness
and apparent exhaustion.
Patients cold, stiff and cyanotic, with fixed pupils and no audible heart tones or visible thoracic excursions have been successfully resuscitated.
The only certain criterion for death in hypothermia is irreversibility of cardiac arrest when the patient is warm.
Conclusions regarding the potential reversibility of coexisting conditions should be withheld until the patient is rewarmed.
Resuscitation, including CPR if necessary, should be continued until either failure after hospital rewarming to 35 degrees Celcius or danger through exposure to rescuers exists.
If medical care is unavailable
start warming the body slowly
warm the body core first
use your own body heat to help
get the victim into dry clothing
and wrap them in a warm blanket covering the head and neck.
Frost bite
-freezing of surface area of the body
-ears, digits of hand/feet
-gangrene
Protection against frost bite – vasodilatation
Artificial hypothermia
-sedation
-depress cns temperature regulating mech.
- ice, cooling blankets
- alcohol
ARTIFICIAL HYPOTHERMIA
Strong sedative-depressing the reactivity of hypothalamic temperature controller
Cooling with ice
Used in heart surgery
Organ transport
Friday, January 4, 2008
slides blod clot
Hemostasis
- prevention of blood loss
Mechanism of hemostasis
1. vascular spasm
2. formation of platelet plug
3. formation of blood clot
4. growth of fibrous tissue
Vasoconstriction
Vessel wall contracts after wounding
Causes of contraction
1. nervous reflex
2. myogenic spasm
3. release of local humoral factors
Thromboxane A2 – release from platelets
Platelet plug formation
Physical and chemical properties of platelets
-minute oval discs 2 -4 micrometers
-cytoplasmic factors
1. actin and moysin molecules
2. thrombosthenin
3. calcium in ER and golgi app
4. enzymes producing prostaglandin
5. fibrin stabilizing factors
6. growth factors
Mechanism
Contact with damaged vascular wall – collagen and endothelial cells
Platelets swell with pseudopods
Contractile proteins contract
Release of granules with multiple active factors
Adp and thromboxane A2 activate other platelets becoming sticky
Additional platelets adhering to original platelets
Formation of plug
Importance of platelet plug
Platelet plug is enough to stop bleeding from small vascular rent
Minute rupture of small blood vessel occurs everyday
Decrease in platelet count can result to small hemorrhages in skin and other tissues
Blood coagulation in ruptured blood vessel
Begins to develop in 15-20 seconds (severe)
1 – 2 mins. If minor trauma
Activator substances released from
traumatized vascular wall
platelets
blood proteins
Clot is formed in 3-6 mins.
Clot retraction occurs after 20 mins to an hour
Clot retraction is a function of platelets
Fibrous tissue organization of dissolution
2 courses that can occur after a clot is formed
1. invaded by fibroblasts
2. it can dissolved
Growth factor
Mechanism of blood coagulation
Presence of procoagulant and anticoagulant
General mechanism
1. formation of prothrombin activator
2. conversion of prothrombin to thrombin
3. conversion of fibrinogen to fibrin fibers
Convertion of prothrombin to thrombin
prothrombin
Prothrombin activator Ca++
thrombin
fibrinogen fibrinogen monomer
Thrombin activated fibrin fibers
Fibrin-stabilaizing
Factor
cross-linked fibrin fibers
formation of clot
Clot is a meshwork of fibrin fibers entrapping blood cells, platelets and plasma
Clot retraction – contracts minutes after clot is formed
-- expresses fluid out in 20-60 mins
-- serum—plasma devoid of clotting factors
-- function of platelets – release of
thrombosthenin
actin myosin
initiation of coagulation
2 ways of forming prothrombin activator
1. by extrinsic pathway – trauma to vascular wall
and surrounding tissue
2. by intrinsic pathway – trauma to blood itself
facilitated by plasma protein– blood clotting factors
-- inactive forms of proteolytic enzymes
Extrinsic pathway
Tissue trauma
Tissue factor
VII
VIIa
X activated X
Ca++ Ca++
V
prothrombin activator
platelet phospholipid
prothrombin thrombin
Ca++
Intrinsic pathway
BLOOD TRAUMA OR CONTACT WITH COLLAGEN
XII activated XII
HMW kinogen,prekallikrein
XI activated XI
Ca++
IX activated X
VIII
Thrombin Ca++ Ca++
VIIIa
X activated X prothrombin activator
platelet thrombin
phospholipid V
prothrombin thrombin
Ca++
Role of calcium
Except for first 2 steps calcium ions are required in cascading reaction
Absence of calcium ions- no clot formation
Calcium ion level can be reduced to prevent clot formation
Citrate ion – deionize cacium
Oxalate ion -- precipitate calcium
Prevention of clotting
Endothelial surface factors
1. smoothness of the endothelial lining
2. layer of glycocalyx
3. thrombomodulin – binds thrombin – complex –
activates protein C that inhibits
factor V and VIII
Antithrombin action of fibrin and antithrombin III
- fibrin traps most thrombin
- unabsorbed thrombin neutralized by antithrombin III
Heparin – produce by basophilic mast cell
-- powerful anticoagulant – on its own it is weak - -combines with antithrombin III increasing efficacy as
anticoagulant
lysis of blood clot
Plasminogen – plasma protein - activated becomes plasmin
Plasmin – enzyme digesting fibrin fibers and other factors
Tissue plasminogen activator – release by injured tissue
and activates plasminogen trapped in the
clot
conditions that cause bleeding
Deficiency of any one of the blood clotting factors
Most common conditions
1. vitamin K deficiency
2. hemophilia
3. thrombocytopenia
Vit. K
MOST BLOOD CLOTTING FACTORS ARE FORMED IN THE LIVER
AFFECTION OF THE LIVER MAY LEAD TO BLEEDING PROBLEM
ROLE OF VITAMIN k
--NECESSARY IN SYNTHESIS OF: FACTORS II,VII,IX,X
--NORMALLY PRODUCE BY BACTERIA IN INTESTINE
-- FAT SOLUBLE THUS ABSORBED WITH FATS
-- BILE NEEDED FOR FAT ABSORPTION
-- FAILURE OF BILE TO PASS THRU INTESTINE THUS
CAN AFFECT ABSORPTION OF VIT. K
Hemophilia
Bleeding disorder occurring in male
Deficiency in factor VIII in 85% of cases
Others cause by deficiency of factor IX
Transmitted by way of X chromosomes as a
recessive trait
bleeding occurs after trauma
treatment – transfusion of factor VIII
thrombocytopenia
Very low quantity of platelets
Bleeding usually from small venules and capillaries
Manifests as small punctate hemorrhage
Spontaneous bleeding - <50,000>
- prevention of blood loss
Mechanism of hemostasis
1. vascular spasm
2. formation of platelet plug
3. formation of blood clot
4. growth of fibrous tissue
Vasoconstriction
Vessel wall contracts after wounding
Causes of contraction
1. nervous reflex
2. myogenic spasm
3. release of local humoral factors
Thromboxane A2 – release from platelets
Platelet plug formation
Physical and chemical properties of platelets
-minute oval discs 2 -4 micrometers
-cytoplasmic factors
1. actin and moysin molecules
2. thrombosthenin
3. calcium in ER and golgi app
4. enzymes producing prostaglandin
5. fibrin stabilizing factors
6. growth factors
Mechanism
Contact with damaged vascular wall – collagen and endothelial cells
Platelets swell with pseudopods
Contractile proteins contract
Release of granules with multiple active factors
Adp and thromboxane A2 activate other platelets becoming sticky
Additional platelets adhering to original platelets
Formation of plug
Importance of platelet plug
Platelet plug is enough to stop bleeding from small vascular rent
Minute rupture of small blood vessel occurs everyday
Decrease in platelet count can result to small hemorrhages in skin and other tissues
Blood coagulation in ruptured blood vessel
Begins to develop in 15-20 seconds (severe)
1 – 2 mins. If minor trauma
Activator substances released from
traumatized vascular wall
platelets
blood proteins
Clot is formed in 3-6 mins.
Clot retraction occurs after 20 mins to an hour
Clot retraction is a function of platelets
Fibrous tissue organization of dissolution
2 courses that can occur after a clot is formed
1. invaded by fibroblasts
2. it can dissolved
Growth factor
Mechanism of blood coagulation
Presence of procoagulant and anticoagulant
General mechanism
1. formation of prothrombin activator
2. conversion of prothrombin to thrombin
3. conversion of fibrinogen to fibrin fibers
Convertion of prothrombin to thrombin
prothrombin
Prothrombin activator Ca++
thrombin
fibrinogen fibrinogen monomer
Thrombin activated fibrin fibers
Fibrin-stabilaizing
Factor
cross-linked fibrin fibers
formation of clot
Clot is a meshwork of fibrin fibers entrapping blood cells, platelets and plasma
Clot retraction – contracts minutes after clot is formed
-- expresses fluid out in 20-60 mins
-- serum—plasma devoid of clotting factors
-- function of platelets – release of
thrombosthenin
actin myosin
initiation of coagulation
2 ways of forming prothrombin activator
1. by extrinsic pathway – trauma to vascular wall
and surrounding tissue
2. by intrinsic pathway – trauma to blood itself
facilitated by plasma protein– blood clotting factors
-- inactive forms of proteolytic enzymes
Extrinsic pathway
Tissue trauma
Tissue factor
VII
VIIa
X activated X
Ca++ Ca++
V
prothrombin activator
platelet phospholipid
prothrombin thrombin
Ca++
Intrinsic pathway
BLOOD TRAUMA OR CONTACT WITH COLLAGEN
XII activated XII
HMW kinogen,prekallikrein
XI activated XI
Ca++
IX activated X
VIII
Thrombin Ca++ Ca++
VIIIa
X activated X prothrombin activator
platelet thrombin
phospholipid V
prothrombin thrombin
Ca++
Role of calcium
Except for first 2 steps calcium ions are required in cascading reaction
Absence of calcium ions- no clot formation
Calcium ion level can be reduced to prevent clot formation
Citrate ion – deionize cacium
Oxalate ion -- precipitate calcium
Prevention of clotting
Endothelial surface factors
1. smoothness of the endothelial lining
2. layer of glycocalyx
3. thrombomodulin – binds thrombin – complex –
activates protein C that inhibits
factor V and VIII
Antithrombin action of fibrin and antithrombin III
- fibrin traps most thrombin
- unabsorbed thrombin neutralized by antithrombin III
Heparin – produce by basophilic mast cell
-- powerful anticoagulant – on its own it is weak - -combines with antithrombin III increasing efficacy as
anticoagulant
lysis of blood clot
Plasminogen – plasma protein - activated becomes plasmin
Plasmin – enzyme digesting fibrin fibers and other factors
Tissue plasminogen activator – release by injured tissue
and activates plasminogen trapped in the
clot
conditions that cause bleeding
Deficiency of any one of the blood clotting factors
Most common conditions
1. vitamin K deficiency
2. hemophilia
3. thrombocytopenia
Vit. K
MOST BLOOD CLOTTING FACTORS ARE FORMED IN THE LIVER
AFFECTION OF THE LIVER MAY LEAD TO BLEEDING PROBLEM
ROLE OF VITAMIN k
--NECESSARY IN SYNTHESIS OF: FACTORS II,VII,IX,X
--NORMALLY PRODUCE BY BACTERIA IN INTESTINE
-- FAT SOLUBLE THUS ABSORBED WITH FATS
-- BILE NEEDED FOR FAT ABSORPTION
-- FAILURE OF BILE TO PASS THRU INTESTINE THUS
CAN AFFECT ABSORPTION OF VIT. K
Hemophilia
Bleeding disorder occurring in male
Deficiency in factor VIII in 85% of cases
Others cause by deficiency of factor IX
Transmitted by way of X chromosomes as a
recessive trait
bleeding occurs after trauma
treatment – transfusion of factor VIII
thrombocytopenia
Very low quantity of platelets
Bleeding usually from small venules and capillaries
Manifests as small punctate hemorrhage
Spontaneous bleeding - <50,000>
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