NEET MDS Lessons
Physiology
Events in Muscle Contraction - the sequence of events in crossbridge formation:
1) In response to Ca2+ release into the sarcoplasm, the troponin-tropomyosin complex removes its block from actin, and the myosin heads immediately bind to active sites.
2) The myosin heads then swivel, the Working Stroke, pulling the Z-lines closer together and shortening the sarcomeres. As this occurs the products of ATP hydrolysis, ADP and Pi, are released.
3) ATP is taken up by the myosin heads as the crossbridges detach. If ATP is unavailable at this point the crossbridges cannot detach and release. Such a condition occurs in rigor mortis, the tensing seen in muscles after death, and in extreme forms of contracture in which muscle metabolism can no longer provide ATP.
4) ATP is hydrolyzed and the energy transferred to the myosin heads as they cock and reset for the next stimulus.
Excitation-Contraction Coupling: the Neuromuscular Junction
Each muscle cell is stimulated by a motor neuron axon. The point where the axon terminus contacts the sarcolemma is at a synapse called the neuromuscular junction. The terminus of the axon at the sarcolemma is called the motor end plate. The sarcolemma is polarized, in part due to the unequal distribution of ions due to the Sodium/Potassium Pump.
1) Impulse arrives at the motor end plate (axon terminus) causing Ca2+ to enter the axon.
2) Ca2+ binds to ACh vesicles causing them to release the ACh (acetylcholine) into the synapse by exocytosis.
3) ACH diffuses across the synapse to bind to receptors on the sarcolemma. Binding of ACH to the receptors opens chemically-gated ion channels causing Na+ to enter the cell producing depolarization.
4) When threshold depolarization occurs, a new impulse (action potential) is produced that will move along the sarcolemma. (This occurs because voltage-gated ion channels open as a result of the depolarization -
5) The sarcolemma repolarizes:
a) K+ leaves cell (potassium channels open as sodium channels close) returning positive ions to the outside of the sarcolemma. (More K+ actually leaves than necessary and the membrane is hyperpolarized briefly. This causes the relative refractory period) (b) Na+/K+ pump eventually restores resting ion distribution. The Na+/K+ pump is very slow compared to the movement of ions through the ion gates. But a muscle can be stimulated thousands of times before the ion distribution is substantially affected.
6) ACH broken down by ACH-E (a.k.a. ACHase, cholinesterase). This permits the receptors to respond to another stimulus.
Excitation-Contraction Coupling:
1) The impulse (action potential) travels along the sarcolemma. At each point the voltaged-gated Na+ channels open to cause depolarization, and then the K+ channels open to produce repolarization.
2) The impulse enters the cell through the T-tublules, located at each Z-disk, and reach the sarcoplasmic reticulum (SR), stimulating it.
3) The SR releases Ca2+ into the sarcoplasm, triggering the muscle contraction as previously discussed.
4) Ca2+ is pumped out of the sarcoplasm by the SR and another stimulus will be required to continue the muscle contraction.
PHYSIOLOGY OF THE BRAIN
- The Cerebrum (Telencephalon) Lobes of the cerebral cortex
- Frontal Lobe
- Precentral gyrus, Primary Motor Cortex, point to point motor neurons, pyramidal cells: control motor neurons of the brain and spinal cord. See Motor homunculus
- Secondary Motor Cortex repetitive patterns
- Broca's Motor Speech area
- Anterior - abstract thought, planning, decision making, Personality
- Parietal Lobe
- Post central gyrus, Sensory cortex, See Sensory homunculus, size proportional to sensory receptor density.
- Sensory Association area, memory of sensations
- Occipital Lobe
- Visual cortex, sight (conscious perception of vision)
- Visual Association area, correlates visual images with previous images, (memory of vision, )
- Temporal Lobe
- Auditory Cortex, sound
- Auditory Association area, memory of sounds
- Common Integratory Center - angular gyrus, Parietal, Temporal & Occipital lobes
- One side becomes dominent, integrats sensory (somesthetic, auditory, visual) information
- The Basal nuclei (ganglia)
- Grey matter (cell bodies) within the White matter of cerebrum, control voluntary movements
- Cauadate nucles - chorea (rapi, uncontrolled movements), Parkinsons: (dopamine neurons of substantia nigra to caudate nucles) jerky movements, spasticity, tremor, blank facial expression
- The limbic system - ring around the brain stem, emotions(w/hypothalamus), processing of olfactory information
- Frontal Lobe
- The Diencephalon
- The Thalamus - Sensory relay center to cortex (primitive brain!)
- The Hypothalamus
- core temperature control"thermostat", shivering and nonshivering thermogenesis
- hunger & satiety centers, wakefulness, sleep, sexual arousal,
- emotions (w/limbic-anger, fear, pain, pleasure), osmoregulation, (ADH secretion),
- Secretion of ADH, Oxytocin, Releasing Hormones for Anterior pitutary
- Linkage of nervous and endocrine systems
- The Mesencephalon or Midbrain -
- red nucleus, motor coordination (cerebellum/Motor cortex),
- substantia nigra
- The Metencephalon
- The Cerebellum -
- Performs automatic adjustments in complex motor activities
- Input from Proprioceptors (joint, tendon, muscles), position of body in Space
- Motor cortex, intended movements (changes in position of body in Space)
- Damping (breaking motor function), Balance, predicting, inhibitory function of Purkinji cells (GABA), speed, force, direction of movement
- The Pons - Respiratory control centers (apneustic, pneumotaxic)
- Nuclei of cranial nerves V, VI, VII, VIII
- The Cerebellum -
- Myelencephalon
- The Medulla
- Visceral motor centers (vasomotor, cardioinhibtory, respiratory)
- Reticular Formation RAS system, alert cortex to incoming signals, maintenance of consciousness, arousal from sleep
- All Afferent & Efferent fibers pass through, crossing over of motor tracts
- Corpus Callosum: Permits communication between cerebralhemispheres
- The Medulla
- Generalized Brain Avtivity
- Brain Activity and the Electroencephalogram(EEG)
- alpha waves: resting adults whose eyes are closed
- beta waves: adults concentrating on a specific task;
- theta waves: adults under stress;
- delta waves: during deep sleep and in clinical disorders
- Brain Seizures
- Grand Mal: generalized seizures, involvs gross motor activity, affects the individual for a matter or hours
- Petit mal: brief incidents, affect consciousness but may have no obvious motor abnormalities
- Chemical Effects on the Brain
- Sedatives: reduce CNS activity
- Analgesics: relieve pain by affecting pain pathways or peripheral sensations
- Psychotropics: alter mood and emotional states
- Anticonvulsants: control seizures
- Stimulants: facilitate CNS activity
- Memory and learning
- Short-term, or primary, memories last a short time, immediately accessible (phone number)
- Secondary memories fade with time (your address at age 5)
- Tertiary memories last a lifetime (your name)
- Memories are stored within specific regions of the cerebral cortex.
- Learning, a more complex process involving the integration of memories and their use to direct or modify behaviors
- Neural basis for memory and learning has yet to be determined.
- Brain Activity and the Electroencephalogram(EEG)
- Fibers in CNS
- Association fibers: link portions of the cerebrum;
- Commissural fibers: link the two hemispheres;
- Projection fibers: link the cerebrum to the brain stem
1. Automatic control (sensory) of respiration is in - brainstem (midbrain)
2. Behavioral/voluntary control is in - the cortex
3. Alveolar ventilation -the amount of atmospheric air that actually reaches the alveolar per breath and that can participate in the exchange of gasses between alveoli and blood
4. Only way to increase gas exchange in alveolar capillaries - perfusion-limited gas exchange
5. Pulmonary ventiliation not effected by - concentration of bicarbonate ions
6. Central chemoreceptors - medulla - CO2, O2 and H+ concentrations
7. Peripheral chemoreceptors - carotid and aortic bodies- PO2, PCO2 and pH
8. Major stimulus for respiratory centers - arterial PCO2
9. Rhythmic breathing depends on
1. continuous (tonic) inspiratory drive from DRG (dorsal respiratory group)
2. intermittent (phasic) expiratory input from cerebrum, thalamus, cranial nerves and ascending spinal cord sensory tracts
10. Primary site for gas exchange - type I epithelial cells for alveoli
The Body Regulates pH in Several Ways
- Buffers are weak acid mixtures (such as bicarbonate/CO2) which minimize pH change
- Buffer is always a mixture of 2 compounds
- One compound takes up H ions if there are too many (H acceptor)
- The second compound releases H ions if there are not enough (H donor)
- The strength of a buffer is given by the buffer capacity
- Buffer capacity is proportional to the buffer concentration and to a parameter known as the pK
- Mouth bacteria produce acids which attack teeth, producing caries (cavities). People with low buffer capacities in their saliva have more caries than those with high buffer capacities.
- Buffer is always a mixture of 2 compounds
- CO2 gas (a potential acid) is eliminated by the lungs
- Other acids and bases are eliminated by the kidneys
Typical Concentration Gradients and Membrane Potentials in Excitable Cells
The Na Pump is Particularly Important in the Kidney and Brain
- All cells have Na pumps in their membranes, but some cells have more than others
- Over-all Na pump activity may account for a third of your resting energy expenditure!
- In the kidney the Na pump activity is very high because it is used to regulate body salt and water concentrations
- Kidneys use enormous amounts of energy: 0.5% of body weight, but use 7% of the oxygen supply
- Pump activity is also high in the brain because Na and K gradients are essential for nerves
- The brain is another high energy organ; it is 2% of body weight, but uses 18% of the oxygen supply
In the Resting State Potassium Controls the Membrane Potential of Most Cells
- Resting cells have more open K channels than other types
- More K+ passes through membrane than other ions- therefore K+ controls the potential
- Blood K+ must be closely controlled because small changes will produce large changes in the membrane potentials of cells
- Raising K will make the membrane potential less negative (depolarization)
- High blood K+ can cause the heart to stop beating (it goes into permanent contraction)
During an Action Potential Na Channels Open, and Na Controls the Membrane Potential
- Whichever ion has the most open channels controls the membrane potential
- Excitable cells have Na channels that open when stimulated
- When large numbers of these channels open Na controls the membrane potential
A heart rate that is persistently greater than 100bpm is termed tachycardia. A heart rate that is persistantly lower than 60 pulse per min is termed bradycardia. Let's examine some factors that could cause a change in heart rate:
- Increased heart rate can be caused by:
- Increased output of the cardioacceleratory center. In other words, greater activity of sympathetic nerves running to the heart and a greater release of norepinephrine on the heart.
- Decreased output of the cardioinhibitory center. In other words, less vagus nerve activity and a decrease in the release of acetylcholine on the heart.
- Increased release of the hormone epinephrine by the adrenal glands.
- Nicotine.
- Caffeine.
- Hyperthyroidism - i.e., an overactive thyroid gland. This would lead to an increased amount of the hormone thyroxine in the blood.
- Decreased heart rate can be caused by:
- Decreased activity of the cardioacceleratory center.
- Increased activity of the cardioinhibitory center.
- Many others.
Serum Lipids
LIPID |
Typical values (mg/dl) |
Desirable (mg/dl) |
Cholesterol (total) |
170–210 |
<200 |
LDL cholesterol |
60–140 |
<100 |
HDL cholesterol |
35–85 |
>40 |
Triglycerides |
40–160 |
<160 |
- Total cholesterol is the sum of
- HDL cholesterol
- LDL cholesterol and
- 20% of the triglyceride value
- Note that
- high LDL values are bad, but
- high HDL values are good.
- Using the various values, one can calculate a
cardiac risk ratio = total cholesterol divided by HDL cholesterol - A cardiac risk ratio greater than 7 is considered a warning.