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.
Membrane Structure & Function
Cell Membranes
- Cell membranes are phospholipid bilayers (2 layers)
- Bilayer forms a barrier to passage of molecules in an out of cell
- Phospholipids = glycerol + 2 fatty acids + polar molecule (i.e., choline) + phosphate
- Cholesterol (another lipid) stabilizes cell membranes
- the hydrophobic tails of the phospholipids (fatty acids) are together in the center of the bilayer. This keeps them out of the water
Membranes Also Contain Proteins
- Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long
- Hydrophobic = doesn't like water = likes lipids
- Membrane proteins have many functions:
- receptors for hormones
- pumps for transporting materials across the membrane
- ion channels
- adhesion molecules for holding cells to extracellular matrix
cell recognition antigens
The nephron of the kidney is involved in the regulation of water and soluble substances in blood.
A Nephron
A nephron is the basic structural and functional unit of the kidneys that regulates water and soluble substances in the blood by filtering the blood, reabsorbing what is needed, and excreting the rest as urine.
Its function is vital for homeostasis of blood volume, blood pressure, and plasma osmolarity.
It is regulated by the neuroendocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.
The Glomerulus
The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. Here, fluid and solutes are filtered out of the blood and into the space made by Bowman's capsule.
A group of specialized cells known as juxtaglomerular apparatus (JGA) are located around the afferent arteriole where it enters the renal corpuscle. The JGA secretes an enzyme called renin, due to a variety of stimuli, and it is involved in the process of blood volume homeostasis.
The Bowman's capsule surrounds the glomerulus. It is composed of visceral (simple squamous epithelial cells; inner) and parietal (simple squamous epithelial cells; outer) layers.
Red blood cells and large proteins, such as serum albumins, cannot pass through the glomerulus under normal circumstances. However, in some injuries they may be able to pass through and can cause blood and protein content to enter the urine, which is a sign of problems in the kidney.
Proximal Convoluted Tubule
The proximal tubule is the first site of water reabsorption into the bloodstream, and the site where the majority of water and salt reabsorption takes place. Water reabsorption in the proximal convoluted tubule occurs due to both passive diffusion across the basolateral membrane, and active transport from Na+/K+/ATPase pumps that actively transports sodium across the basolateral membrane.
Water and glucose follow sodium through the basolateral membrane via an osmotic gradient, in a process called co-transport. Approximately 2/3rds of water in the nephron and 100% of the glucose in the nephron are reabsorbed by cotransport in the proximal convoluted tubule.
Fluid leaving this tubule generally is unchanged due to the equivalent water and ion reabsorption, with an osmolarity (ion concentration) of 300 mOSm/L, which is the same osmolarity as normal plasma.
The Loop of Henle
The loop of Henle is a U-shaped tube that consists of a descending limb and ascending limb. It transfers fluid from the proximal to the distal tubule. The descending limb is highly permeable to water but completely impermeable to ions, causing a large amount of water to be reabsorbed, which increases fluid osmolarity to about 1200 mOSm/L. In contrast, the ascending limb of Henle's loop is impermeable to water but highly permeable to ions, which causes a large drop in the osmolarity of fluid passing through the loop, from 1200 mOSM/L to 100 mOSm/L.
Distal Convoluted Tubule and Collecting Duct
The distal convoluted tubule and collecting duct is the final site of reabsorption in the nephron. Unlike the other components of the nephron, its permeability to water is variable depending on a hormone stimulus to enable the complex regulation of blood osmolarity, volume, pressure, and pH.
Normally, it is impermeable to water and permeable to ions, driving the osmolarity of fluid even lower. However, anti-diuretic hormone (secreted from the pituitary gland as a part of homeostasis) will act on the distal convoluted tubule to increase the permeability of the tubule to water to increase water reabsorption. This example results in increased blood volume and increased blood pressure. Many other hormones will induce other important changes in the distal convoluted tubule that fulfill the other homeostatic functions of the kidney.
The collecting duct is similar in function to the distal convoluted tubule and generally responds the same way to the same hormone stimuli. It is, however, different in terms of histology. The osmolarity of fluid through the distal tubule and collecting duct is highly variable depending on hormone stimulus. After passage through the collecting duct, the fluid is brought into the ureter, where it leaves the kidney as urine.
Neural Substrates of Breathing
A. Medulla Respiratory Centers
Inspiratory Center (Dorsal Resp Group - rhythmic breathing) → phrenic nerve→ intercostal nerves→ diaphragm + external intercostals
Expiratory Center (Ventral Resp Group - forced expiration) → phrenic nerve → intercostal nerves → internal intercostals + abdominals (expiration)
1. eupnea - normal resting breath rate (12/minute)
2. drug overdose - causes suppression of Inspiratory Center
B. Pons Respiratory Centers
1. pneumotaxic center - slightly inhibits medulla, causes shorter, shallower, quicker breaths
2. apneustic center - stimulates the medulla, causes longer, deeper, slower breaths
C. Control of Breathing Rate & Depth
1. breathing rate - stimulation/inhibition of medulla
2. breathing depth - activation of inspiration muscles
3. Hering-Breuer Reflex - stretch of visceral pleura that lungs have expanded (vagal nerve)
D. Hypothalamic Control - emotion + pain to the medulla
E. Cortex Controls (Voluntary Breathing) - can override medulla as during singing and talking
AdenosineTriphosphate (ATP)
- Animal cells cannot directly use most forms of energy
- Most cellular processes require energy stored in the bonds of a molecule, adenosine triphosphate (ATP)
- ATP is referred to as the energy currency of the cell
It is a nucleotide, formed from:
- the base adenine (the structure with 2 rings),
- the 5 carbon sugar deoxyribose (one ring)
- 3 phosphates
Energy is stored in the bonds between the phosphates and is released when the bonds are broken
Pain, Temperature, and Crude Touch and Pressure
General somatic nociceptors, thermoreceptors, and mechanoreceptors sensitive to crude touch and pressure from the face conduct signals to the brainstem over GSA fibers of cranial nerves V, VII, IX, and X.
The afferent fibers involved are processes of monopolar neurons with cell bodies in the semilunar, geniculate, petrosal, and nodose ganglia, respectively.
The central processes of these neurons enter the spinal tract of V, where they descend through the brainstem for a short distance before terminating in the spinal nucleus of V.
Second-order neurons then cross over the opposite side of the brainstem at various levels to enter the ventral trigeminothalamic tract, where they ascend to the VPM of the thalamus.
Finally, third-order neurons project to the "face" area of the cerebral cortex in areas 3, 1, and 2 .
Discriminating Touch and Pressure
Signals are conducted from general somatic mechanoreceptors over GSA fibers of the trigeminal nerve into the principal sensory nucleus of V, located in the middle pons.
Second-order neurons then conduct the signals to the opposite side of the brainstem, where they ascend in the medial lemniscus to the VPM of the thalamus.
Thalamic neurons then project to the "face" region of areas 3, I, and 2 of the cerebral cortex.
Kinesthesia and Subconscious Proprioception
Proprioceptive input from the face is primarily conducted over GSA fibers of the trigeminal nerve.
The peripheral endings of these neurons are the general somatic mechanoreceptors sensitive to both conscious (kinesthetic) and subconscious proprioceptive input.
Their central processes extend from the mesencephalic nucleus to the principal sensory nucleus of V in the pons
The subconscious component is conducted to the cerebellum, while the conscious component travels to the cerebral cortex.
Certain second-order neurons from the principal sensory nucleus relay proprioceptive information concerning subconscious evaluation and integration into the ipsilateral cerebellum.
Other second-order neurons project to the opposite side of the pons and ascend to the VPM of the thalamus as the dorsal trigeminothalamic tract.
Thalamic projections terminate in the face area of the cerebral cortex.
Gonadotropin-releasing hormone (GnRH)
GnRH is a peptide of 10 amino acids. Its secretion at the onset of puberty triggers sexual development.
Primary Effects
FSH and LH Relaese
Secondary Effects
Increases estrogen and progesterone (in females)
testosterone Relaese (in males)
Growth hormone-releasing hormone (GHRH)
GHRH is a mixture of two peptides, one containing 40 amino acids, the other 44. GHRH stimulates cells in the anterior lobe of the pituitary to secrete growth hormone (GH).
Corticotropin-releasing hormone (CRH)
CRH is a peptide of 41 amino acids. Its acts on cells in the anterior lobe of the pituitary to release adrenocorticotropic hormone (ACTH) CRH is also synthesized by the placenta and seems to determine the duration of pregnancy. It may also play a role in keeping the T cells of the mother from mounting an immune attack against the fetus
Somatostatin
Somatostatin is a mixture of two peptides, one of 14 amino acids, the other of 28. Somatostatin acts on the anterior lobe of the pituitary to
- inhibit the release of growth hormone (GH)
- inhibit the release of thyroid-stimulating hormone (TSH)
Somatostatin is also secreted by cells in the pancreas and in the intestine where it inhibits the secretion of a variety of other hormones.
Antidiuretic hormone (ADH) and Oxytocin
These peptides are released from the posterior lobe of the pituitary