Findyourself343 | notes for medical topics

ACTION POTENTIAl:

Stimulus:

A stimulus is an external force or event which when applied to an excitable tissue produces a characteristic response.

Subthreshold stimulus:

A stimulus which is too weak to produce a response is called a Subthreshold stimulus.

Threshold stimulus:

The minimum strength of stimulus that can produce excitation is called a Threshold stimulus.

Suprathreshold stimulus:

Stimuli having strengths higher than threshold stimulus are called Suprathreshold stimuli.

• Sodium voltage-gated channels: are fast channels & have 2 gates:

- An outer Activation gate (closed in resting state)

- An Inner Inactivation gate (open in resting state)

• Potassium channels are slow channels & have only ONE gate.

• These channels are different from Sodium & Potassium leak channels.

• The Sodium-Potassium PUMP is present separately.

Action Potential:

An Action Potential is a self-propagating wave of electro-negativity that passes along the surface of the axolemma of the nerve fibers.

• We know that the inside of the nerve membrane is negative with respect to the outside (RMP=—90 mv)

• When an effective stimulus (threshold or suprathreshold) is applied, the electrical charge on the membrane is reversed: at the active part of the nerve fibre the outside becomes negative as compared to the corresponding region in the interior. This is called DEPOLARIZATION and forms the Action Potential.

PHASES OF AN ACTION POTENTIAL:

Phase 1: Depolarization

Phase 2: Repolarization

Phase 3: Hyperpolarization

1. DEPOLARIZATION: Sodium (Na) Influx

2. REPOLARIZATION: Potassium (K) Efflux

3. HYPERPOLARIZATION: Leakage of excess Potassium (K) ions through the slow closing K channels.

4. RETURN OF THE AP TO THE RMP FROM HYPERPOLARIZATION: Sodium-Potassium Pump

• AFTER-DEPOLARIZATION:

The descending limb of the action potential does not reach the baseline abruptly, but it shows a delay of several milliseconds. This is due to decreased rate of K efflux at this time. The excitability & conductivity of the fibre are increased during this phase.

• AFTER-HYPERPOLARIZATION:

Leakage of excess Potassium (K) ions through the slow closing K channels.

Why does the depolarization not reach the Nernst potential of +66mv for sodium?

There are 2 main reasons. At +35 mv:

• Sodium Influx stops because Inactivation gates of Sodium channels close although the activation gates are open & thus no sodium can enter

• Potassium Efflux starts because slow Potassium channel gates open and potassium moves out.

State of SODIUM channel gates:

• Resting state:

- Inactivation gates: OPEN

- Activation gates: CLOSED

• Depolarization:

- Activation gates: OPEN

- Inactivation gates: OPEN

• Peak:

- Inactivation gates: CLOSED

- Activation gates: OPEN

• Repolarization:

- Inactivation gates: OPEN

- Activation gates: CLOSED

PROPAGATION OF AN ACTION POTENTIAL:

Unmyelinated Nerve fiber

• Once an action potential is initiated at the axon hillock, no further triggering event is necessary to activate the remainder of the nerve fiber. The impulse is automatically conducted throughout the neuron.

• For the action potential to spread from the active to the inactive areas, the inactive areas must somehow be depolarized to threshold. This depolarization is accomplished by local current flow between the area already undergoing an action potential and the adjacent inactive area

• This depolarizing effect quickly brings the involved inactive area to threshold, at which time the voltage-gated Na channels in this region of the membrane are all thrown open, leading to an action potential in this previously inactive area. Meanwhile, the original active area returns to resting potential as a result of K+ efflux.

2 Comments

Respiratory Physiology

Functions of Respiratory System

• Exchange of gases between atmosphere and the blood

• Homeostatic regulation of body pH

• Protection from inhaled pathogens and irritating substances

• Lungs contain lymphocytes, plasma cells and macrophages

• Vocalization

• Loss of water and heat from body

• It enhances venous return ( Respiratory pump)

• The nose as a part of respiratory system, serves as the organ of smell

• Lungs synthesize certain prostaglandins, histamine, heparin and kallekrein

• Pulmonary capillary endothelial cells contain Angiotensin converting enzyme

• Lungs act as reservoir of blood

• Lungs synthesize surfactant

• Pulmonary vessels can trap fat cells, small clots and detached cancer cells and thus prevent their entry into systemic circulation

External Respiration

1. Movement of air from environment / atmosphere to lungs/ alveoli

2. From alveoli to blood

3. Transport in the blood

4. From blood into cells

5. Regulation of respiration

Functional anatomy of respiratory system

Nose or Mouth -- Pharynx -- Larynx --

Trachea -- Bronchi -- Smaller Bronchi --

Terminal Bronchioles -- Respiratory Bronchioles -- Alveolar Ducts -- Alveolar sacs -- Alveoli

• Alveoli are thin-walled, Inflatable, grapelike sacs at the terminal branches of conducting airways

• Each contain single layer of epithelial cells

• Epithelial cells are two types

(a) Type I cells -- for gas exchange, large and occupy 95% of alveolar surface area (Pneumocyte type I )

(b) Type II cells -- Secrete surfactant ( small cells)

(Pneumocyte type II )

q Alveolar macrophages

Pleural sacs

• It is a double- walled closed sac that separates each lung from the thoracic wall and other surrounding structures

Two types:

(1) Visceral Pleura

(2) Parietal Pleura

Gas Laws

1. The total Pressure of a mixture of gases is the sum of the pressures of the individual gases (Dalton’s Law).

2. Gases, singly or in a mixture, move from areas of higher pressure to areas of lower pressure.

3. If the volume of a container of gas changes, the pressure of the gas will change in an inverse manner ( Boyle’s Law)

4. The amount of a gas that will dissolve in a liquid is determined by the partial pressure of the gas and the gas’s solubility in the liquid

Pulmonary Ventilation

Pulmonary ventilation is defined as inflow & outflow of air between the atmosphere & the lung alveoli

Inflow à Inspiration

Outflow à Expiration

Muscles of Inspiration

• External Intercostals

• Sternocleidomastoid

• Anterior serrati

• Scaleni

Muscle of Expiration

• Abdominal Recti

• Internal Intercostals

• Other Abdominal Muscles

2 Comments

SMOOTH MUSCLE

Structure of smooth muscle

• Shape of muscle fiber is spindle shaped

- 1-5 µm in diameter

- 20-500 µm in length

• A single nucleus present in the central thick portion.

• Sarcolemma (cell membrane).

• Cytoplasm appears homogenous without striations.

• Fewer mitochondria as compared to the skeletal muscle.

• Metabolism mostly glycolytic.

• Actin, Myosin & Tropomyosin but NO Troponin

• Dense bodies present attached to the cell membranes OR dispersed throughout the cell

Dense bodies serve the same purpose as the Z-discs

• Attached to the dense bodies are numerous numbers of Actin filaments

• Interspersed between the actin filaments are Myosin filaments ( their diameter twice as much as actin filaments)

Usually, 5-10 times as many actin filaments as Myosin filaments

• SIDEPOLAR CROSS-BRIDGES:

1. Myosin filaments have sidepolar cross-bridges

2. Bridges on one side hinge in one direction & on the other side in the opposite direction

3. Allows myosin to pull an actin filament in one direction while simultaneously pulling it in the other direction on the other side

4. Allow smooth muscle to contract 80% as compared to only 30 % in the skeletal muscle

(Force of contraction in skeletal muscle is limited because of the presence of the z-disc, against which the thick filament against and cannot move any further)

• Calcium Pump: pumps Ca back into the SR if present for relaxation to take place. But it is very slow so that duration of cont. is longer.

• Neuromuscular Junction:

Does not occur in smooth muscle. Instead the autonomic nerves make diffuse junctions that secrete NT into the matrix coating of smooth muscle. A few micrometers away from the muscle fiber

Also the axons supplying them do not have terminal buttons but varicosities on their terminal axons that contain the vesicles containing the NT

• Neurotransmitter:

Apart from Ach, norepinephrine can also be released

Instead of synaptic clefts, smooth muscles have contact junctions

CLASSIFICATION OF SMOOTH MUSCLES

UNITARY/ SINGLE UNIT/SYNCYTIAL/VISCERAL

1. Muscles of visceral organs .e.g. GIT, uterus, ureters & some of the smaller blood vessels.

2. Form a sheet or bundles of tissue.

3. Cell membranes show a gap junction that allows AP to pass rapidly from cell to cell.

4. AP spreads rapidly throughout the sheet of cells – cells contract as a single unit.

MULTI-UNIT

1. Iris & Ciliary body of the eye, large arteries, Piloerector muscles

2. Showing discrete, individual smooth muscle fibers.

3. Smooth muscle cells not electrically linked. Each muscle fiber innervated by a single nerve ending. NT itself can spread and lead to an AP.

4. Selective activation of each muscle fiber that can then contract independently of each other.

Smooth muscle contraction:

When unitary (visceral) smooth m. is stretched, spontaneous AP is usually generated, because:

1. Normal slow potentials caused by stretch

2. Overall ↓ in memb. Negativity caused by stretch

SMOOTH MUSCLE CONTRACTION SEQUENCE OF EVENTS:

· Binding of Ach to the receptors

· Increased Influx of Ca into the cell from the following sources:

· ECF thru Ca channels

· Ca released from SR

· Stretch-activated Ca channels when membrane is deformed

· Chemical-gated Ca channels by NT & hormones

· Ca binds to Calmodulin

· Ca-Calmodulin activates the enzyme: Myosin light chain kinase MLCK or simply Myosin kinase

· Phosphorylation of myosin, using energy & Pi from ATP

· Increased ATPase activity & binding of myosin to actin.

· Contraction of smooth muscle

SMOOTH MUSCLE RELAXATION
SEQUENCE OF EVENTS:

1. Dephosphorylation of Myosin by myosin phosphatase/ MLCP

2. Decreases its ATP activity

3. Ca removed from cytoplasm using Ca-Na antiport protein & Ca-ATPase

4. Calmodulin releases Ca & uncomplexes from MK

5. MK is phosphorylated by Protein kinase, inactivating it

6. Relaxation OR sustained contraction

Latch system

It is a state in which the dephosphrylated myosin remains attached to actin for prolonged period of time. This produces sustained contraction without consuming ATP & thus enables the smooth muscle to sustain long-term maintenance of tone without fatigue. E.g. urinary bladder full of urine.

2 Comments

Drugs that increase or block transmission at the Neuromuscular Junction:

1. Drugs that block release of Acetylcholine.

2. E.g: Botulinum toxin, lack of Ca, excess of Mg.

3. Botulinum prevents the release of Acetylcholine by blocking the fusion of Acetylcholine containing vesicles with the postsynaptic membrane & thus prevents the exocytosis of these vesicles. It has some therapeutic use to relieve pain of pathological contraction.

4. Lack of Calcium also leads to blocking of exocytosis of the secretory vesicles.

2. Drugs that stimulate the muscle fibre by Ach-like Action

• Example: methacholine, carbachol, and nicotine

• They have the same effect on the muscle fiber as does Ach. The difference b/w these drugs and Acetylcholine is that the drugs are NOT destroyed by cholinesterase or are destroyed so slowly that their action often persists for many minutes to several hours.

• The drugs work by causing localized areas of depolarization of the muscle fiber membrane at the motor end plate where the acetylcholine receptors are located. Then, every time the muscle fiber recovers from a previous contraction, these depolarized areas, by virtue of leaking ions, initiate a new action potential. Thus, there is a constant state of muscle spasm.

3. Drugs That Stimulate the Neuromuscular Junction by
Inactivating Acetylcholinesterase.

• Neostigmine, physostigmine, and diisopropyl fluorophosphate

• They inactivate the acetylcholinesterase by combining with it in the synaptic cleft so that it no longer hydrolyzes acetylcholine. Therefore, with each successive nerve impulse, additional acetylcholine accumulates and stimulates the muscle fiber repetitively.

• This causes muscle spasm when even a few nerve impulses reach the muscle. Unfortunately, it can also cause death due to laryngeal spasm, which smothers the person.

• Neostigmine and physostigmine work for a few hours.

• Diisopropyl fluorophosphate is effective for weeks. This makes it a particularly lethal poison with great military potential. It is thus used as a powerful “nerve gas poison”.

4. NON-DEPOLARIZING DRUGS:
Drugs That Block Transmission at the Neuromuscular Junction.

A group of drugs known as curariform drugs e.g. D-tubocurarine can prevent passage of impulses from the nerve ending into the muscle. This is done by competing with the Ach for the receptor sites on the postsynaptic membrane. When this drug is bound to these receptor sites, then Ach cannot act on them, thus preventing sufficient increase in permeability of the muscle membrane channels to initiate an action potential.

It can have some therapeutic uses:

- used with artificial respiration to control convulsions in tetanus.

- used during surgery when complete muscle relaxation is required.

2 Comments

Neuromuscular junction

A NEUROMUSCULAR JUNCTION is an area of contact between a muscle fibre and a neuron.

Fig. An electron micrographic sketch of the junction between a single axon terminal and the muscle fiber membrane.

MOTOR END-PLATE

Definition:

It is the specialized portion of a muscle fibre immediately under a terminal nerve fibre. The nerve fibre invaginates a muscle fibre but lies outside the muscle fibre plasma membrane. The entire structure is called the motor end-plate.

NEUROMUSCULAR JUNCTION

A neuromuscular junction thus consists of:

• Presynaptic terminal (Nerve fibre) with vesicles containing the NT

• A synaptic cleft (20-30 nm wide)

• A synaptic trough or gutter (Muscle fibre) which has numerous folds called subneural clefts.

• Neuroreceptors for the NT.

• The NT at an NMJ is

ACETYLCHOLINE (Ach). TheThe presynaptic membrane of the neuron contains linear dense bars. To each side of the dense bars are protein particles penetrating the neural membrane. These are the voltage-gated calcium channels.

• When an action potential spreads over the terminal, these channels open and allow calcium ions to diffuse from the synaptic space to the interior of the nerve terminal.

• The vesicles then fuse with the neural membrane and empty their acetylcholine into the synaptic space by the process of exocytosis.

• Each Ach receptor complex has a total molecular weight of 275,000.

• Each receptor complex is composed of 5 subunits:

- 2 alpha

- 1 beta

- 1 gamma

- 1 delta.

• The channels remains closed unless 2 Ach molecules attach to the 2 alpha subunits which open the gate.

• The opened acetylcholine channel has a diameter of about 0.65 nanometer, which is large enough to allow the important positive ions— Na+, K+ and Ca++ —to move easily through the opening.

The Steps in Neuromuscular Junction

1. An AP reaches the presynaptic terminal of the NMJ.

2. The change in voltage causes the opening of the voltage-gated calcium channels which cause exocytosis of the Ach containing secretory vesicles.

3. The NT Ach is secreted into the synaptic cleft.

4. Ach crosses the synaptic cleft to reach the subneural clefts which contains the Ligand-gated Ach channel.

5. The channels are activated and open allowing the Na+ to move to the inside of the muscle fiber. As long as the Ach is present in the synaptic cleft, it keeps activating the Ach channels which remain open.

6. The influx of Na+ into the muscle lead to the initiation of the END PLATE POTENTIAL (EPP).

END-PLATE POTENTIAL

• At the motor end-plate, the large influx of the Sodium ions leads to a large number of positive charges pouring into the muscle.

• This creates a local positive potential change inside the muscle fiber membrane, called the end plate potential. It is usually about 50-75 mv.

• In turn, this end plate potential initiates an action potential that spreads along the muscle membrane and thus causes muscle contraction.

Acetylcholine Receptor:

• Each Ach receptor complex has a total molecular weight of 275,000.

• Each receptor complex is composed of 5 subunits:

- 2 alpha

- 1 beta

- 1 gamma

- 1 delta.

• The channels remains closed unless 2 Ach molecules attach to the 2 alpha subunits which open the gate.

• The opened acetylcholine channel has a diameter of about 0.65 nanometer, which is large enough to allow the important positive ions— Na+, K+ and Ca++ —to move easily through the opening.