Comprehensive Material Flashcards
What is the different between the contractile (structural) components of smooth muscle and skeletal muscle?
Smooth muscle,,,
- No troponin
- Myosin heads point in various directions, which allows for multi-directional contraction
- Contains dense bodies instead of z-discs
- Smooth muscle cells can shrink and bulge
Skeletal
- z-discs instead of dense bodies
Describe the actomyosin regualtion of skeletal muscle contraction
- ATP binds to the myosin when it is associated with the actin, resulting in the myosin unbinding from the actin
- The ATP is hydrolyzed, resulting in the return of the myosin to its resting conformation and formation of a cross-bridge
- Phosphate is released, resulting in power stroke, ADP is released, and cycle repeats
- . In order for myosin to bind, Ca2+ must bind to TnC (troponin), resulting in a conformational change that reveals the myosin binding site
Describe the actomyosin regulation of smooth muscle contraction
- Ca2+ comes into cell the from ECM (main source is NOT SR) and binds to calmodulin, activates MLCK, phosphorylates myosin
- Cross bridge sequence occurs that is the same as skeletal muscle, except the power strokes can continue so long as the myosin is phosphorylated
- Ca2+ decreases, MLCK downregulated, dephosphorylation of myosin, which results in relaxation
How does calcium participate in both smooth muscle mechanical events and smooth muscle electrical events
Mechanical was described above
For the electrical events of smooth muscle, Ca2+, which comes from the ECM for smooth muscle, can influx into the cell resulting in depolarization, or it can efflux out of the cell, resulting in repolarization
Type I diabetes: cause, signs, symptoms
Can detect autoantibodies many years before onset of disease (autoimmune disease)
Polyuria, thirst, blurred vision, wt loss, weakness, dizzy, sensory nerve dysfunction (paresthiasis), level of consciousness
Type II diabetes: cause, signs, symptoms
High insulin and normal plasma glucose. Metabolic syndrome (see below). Asymptomatic initially. Infections (from elevated glucose), neuropathy (retinal, peripheral), polyuria, thirst, etc, obesity and metabolic syndrome.
Therapy for Type I diabetes
Diet, patient education, and INSULIN
Therapy for type II diabetes
Diet, pt. education, lots of pharmacological strategies (increase insulin secretion/action by mimicking GLP1, inhibit degradation of GLP1. Inhibit K secretion, etc. etc.) Insulin can be used when other strategies don’t work well
Hypoglycemia symptoms
ANS symptoms - tachycardia, sweating, tremors, nausea, hunger
Neurologic symptoms - confusion, irritable, blurred vision, tired
Hypoglycemia treatment
Glucose/glucagon
Describe ketoacidosis
Insulin deficiency causes mobilization of energy stores which includes ketogenesis and thus metabolic acidosis.
More common in Type I.
Treat by restoring plasma vol., reduce glucose, correct acidosis, replenish electrolytes.
Describe flow, velocity of flow and surface area throughout the vascular system
- The volume of flow is equal at all levels.
- As total cross sectional area increases(arteries to arterioles), the flow velocity decreases. Flow is proportional to pressure gradient, the 4th power of the radius and inversely proportional to viscosity and length of the capillary. Radius has a great impact on the flow. The greater the radius, the greater the flow.
- Capillaries have the maximum surface area with the minimum velocity.
Describe in the form of an equation the relationship between flow, pressure and resistance (Ohm’s Law and Poiseuille’s Law).
Flow=(Pi-Po )/Resistance
Pi = pressure coming in Po = pressure going out
List the parameters that need to be known in order to calculate total peripheral resistance
Total peripheral resistance:
Pi=aortic pressure
Po=right atrial pressure
Cardiac output
TPR=(Pi-Po)/(cardiac output)
List the parameters that need to be known in order to calculate the resistance of the pulmonary circuit
Pulmonary circuit resistance:
Pulmonary artery pressure
Left atrial pressure
Cardiac output
Explain piloerection
Piloerection, “Goosebumps”-arrector pilli muscles will be activated via alpha one receptors and increased sympathetic tone. These are attached to cutaneous hair follicles
What mediates shivering?
Shivering is mediated by primary motor center for shivering in the posterior hypothalamus
How does sympathetic chemical thermogenesis work?
Sympathetic chemical thermogenesis: Norepinephrine and epinephrine stimulate brown fat, which produces heat by oxidative phosphorylation. It doesn’t produce ATP. Sympathetic activation via beta one receptors, possibly beta 3.
What part of the hypothalamus is activated in exposure to cold?
Exposure to cold –> mechanisms for heat gain
Posterior hypothalamus is activated. There is cutaneous vasoconstriction with increased sympathetic tone and alpha one activation
What part of the hypothalamus is activated during heat loss?
Heat Loss: Anterior hypothalamus activated
What are the results of anterior hypothalamus activation?
- Cutaneous dilation occurs, which is mediated by decreased adrenergic tone (decreased norepinephrine), which is decreased activation of Alpha-one receptors.
- Cutaneous blood flow represents the exception to the rule for control, which is normally that organs control their blood flow according to local factors and events, and don’t pay attention to the brain.
- The skin is under central control because it is used for overall regulation of temperature.
What part of the nervous system is involved in thermoregulatory sweating?
General thermoregulatory sweating: sympathetic cholinergic event
What part of the nervous system is involved in anxiety sweating?
Anxiety sweating results from sympathetic adrenergic stimulation of a few sweat glands that have alpha one receptors
What regulates apocrine sweat glands?
Apocrine sweat glands which are in the axillary region are regulated by sympathetic adrenergic control
What is a physiological affect of sweating?
Muscle tone is inhibited, therefore shivering is inhibited. Inhibition of chemical thermogenesis will occur
What is the difference between myelinated and unmyelinated nerves in relation to voltage gated Na+ channels?
- Myelinated= in the nodes of Ranvier
- Unmyelinated= all along the membrane of the nerve
What is the difference between myelinated and unmyelinated nerves in relation to speed of conduction?
Myelinated nerves conduct more rapidly because the action potential can jump from node to node down the axon making the total “distance” of the nerve that must propagate an action potential much shorter. The capacitance is also much lower.
What is the difference between myelinated and unmyelinated nerves in relation to efficiency?
Conduction energy efficient since less membrane generates AP’s less Na+ flows into cell so less work for Na+ - K+ pump
Describe myasthenia gravis
autoimmune disease which reduces the number of acetylcholine receptors at the POSTSYNAPTIC neuromuscular junction
Describe Eaton-Lambert syndrome
Autoimmune attack on voltage gated Ca++ channels in the terminals of somatic motor nerves
PRESYNAPTIC
Describe the effects of botulinum toxin
cleave different spots on either synaptic vesicles or PRESYNAPTIC plasma membrane proteins, which interferes with neurotransmitter release
Describe alpha-bungarotoxin
a peptide from venom of banded krait, irreversibly blocks nAchR
POSTSYNAPTIC
What three glycoproteins are involved in platelet adhesion, activation and aggregation?
Glycoproteins and ligands:
GPIbα: von Willebrand Factor (vWf)
- GPVI: Collagen
- GPIIa/IIIb: Fibrinogen
What three G-protein coupled receptors are involved in platelet adhesion, activation and aggregation?
G protein-coupled receptors and ligands:
- P2Y12: ADP
- Protease activated receptor (PAR): Thrombin
- Thromboxane A2 receptor: Thromboxane A2
Describe the functions of platelet-secreted ADP, serotonin, and thromboxane A2 in coagulation
- ADP: To further activate platelets
- Serotonin: To further activate platelets and to cause vasoconstriction
- Thromboxane A2: To further activate platelets and cause vasoconstriction
Describe the effects of constricting either the afferent or the efferent arteriole on renal blood flow (RBF) and Glomerular Filtration Rate (GFR).
Constrict efferent –> GFR increased, RBF decreased
Constrict afferent –> GFR decreased, RBF decreased
How could you increase the glomerular hydrostatic pressure?
Increase glomerular hydrostatic pressure by vasodilating both efferent and afferent
Give the source of fibroblast growth factor 23 (FGF 23). What is FGF23? What are the effects of FGF23 on the kidney? What stimulates the secretion of FGF23? What are the relationships between FGF23 and parathyroid hormone and calcitriol and their actions?
FGF 23 production stimulated by Vit D Hormone (calcitriol) and elevated P. It is a peptide hormone created by osteoblasts and osteocytes. FGF 23 decreases the reabsorption of P in kidneys, and decreases the production of calcitriol (opposite of PTH).
ANS –> Sympathetic division
i. Sympathetic division
1. Cell bodies of preganglionic neurons are located in the intermediolateral column of the Thoraco-Lumbar section of the spinal cord and in motor nuclei of some cranial nerves.
2. Axons of preganglionic neurons exit via the ventral root with axons from somatic motor neurons.
3. After entering the spinal nerves they travel through the white rami communicantes.
ANS –> Parasympathetic division
Two parts of the parasympathetic:
1 - Cranial outflow-
a. Consists of preganglionic fibers in oculomotor, vagus, facial, and glossopharyngeal.
b. Ganglia lie scattered near target organs.
- Sacral outflow-
a. Parasympathetic fibers destined for pelvic and abdominal viscera.
ANS –> Enteric division
- Collection of nerve plexuses that surround GI, pancreas, and biliary system
- Can function without input from sympathetic or parasympathetic systems
General ANS characteristics
a. Dual innervation: Most organs receive both sympathetic and parasympathetic innervation.
b. Only sympathetics: hair, sweat glands, liver, adrenal glands, kidneys, blood vessels
ANS neurotransmitter synthesis
Cholinergic:
Uptake of choline by CHT (blocked by hemocholiniums), which is conjugated with acetylCoA
Adrenergic:
Tyrosine –> DOPA via tyrosine hydroxylase (blocked by metyrosine) –> synthesis continues IN THE VESICLE, as DOPA –> dopamine –> NorE –> Epi
ANS neurotransmitter storage
Cholinergic:
Vesicle-associated transporter (VAT) stores within vesicles (blocked by Vesamicol)
Adrenergic:
Vesicle monoamine transporter (VMAT) stores in vesicles (inhibited by Reserpine)
Mechanisms of release of neurotransmitters
Cholinergic:
Depolarization –> Ca2+ –> calmodulin/VAMP/SNAP (blocked by botulinum) –> vesicle fusion with membrane
Adrenergic:
Similar to cholinergic exocytosis, except the VAMP is blocked by Bretylium
Mechanisms of termination of actions of cholinergic and adrenergic neurotransmitters
Cholinergic:
Ach degraded by AchE (blocked by AchE inhibitors) –> reuptake of choline
Adrenergic:
Diffusion –> metabolized by liver, reuptake via NET1 –> metabolized by MAO
Muscles of inspiration
Diaphragm – MAIN MUSCLE, moves downward to create negative pressure
External intercostals – pull ribcage up, assisting in deep inspiration
Scaleni and SCMs – elevate the first and second ribs, assisting in deep inspiration
Muscles of expiration
Most often a passive process, due to diaphragmatic relaxation and lung recoil
Abdominal muscles – MOST IMPORTANT, contract to force diaphragm upward
Internal intercostals – lowers ribcage, facilitating expiration
What is FVC?
Forced vital capacity (FVC): total volume of air that can be forcibly expired after a maximal inspiration
What is FEV?
Forced Expiratory Volume (FEV) [n]: FEV1, 2, or 3 is the volume of air that can be forcibly expired in the first, second, or third second, respectively
What is FEV 1/FVC?
FEV1/FVC: fraction of total FVC that can be expelled in the first second; normal = 0.8
What is FEF25-75?
Forced expiratory flow at 25-75% of exhaled VC (FEF25-75): flow rate at 25-75% of exhaled VC
Obstructive lung disease
Obstructive: both FVC and FEV are decreased, but FEV is decreased more, so the ratio also decreases
Restrictive lung disease
Restrictive: both FVC and FEV are decreased, but FVC can be more decreased, so the ratio will either remain about the same, or can actually increase
Describe the main pathophysiological features of chronic asthma
Chronic inflammation of the airway walls leads to structural changes (subepithelial fibrosis, airway smooth muscle hypertrophy and hyperplasia, angiogenesis, and hyperplasia of mucus cells), accumulation of airway secretions, contraction of airway smooth muscle (ASM), decreased V/Q relationship (significant perfusion is traveling to poorly ventilated areas of lungs).
Describe therapeutic
ASM contraction can be counteracted via bronchodilator drugs (beta-adrenergic agents, anticholinergics); however, hypertrophy/ hyperplasia of smooth muscle and accumulation of airway secretions are not readily reversible.
Controller treatments include inhaled corticosteroids, antileukotrienes, long-acting beta-agonists, theophylline, systemic corticosteroids, and anti-IgE treatment.
Recognize key pulmonary function test abnormalities in obstructive lung disorders
Decrease in airflow rates throughout the VC (cardinal abnormality during an asthmatic episode), peak expiratory flow rate (PEFR), FEV1, and maximal mid-expiratory flow rate (MMEFR) are all decreased (these objective measures of flow rate must be obtained), and as the attack resolves, it is likely that the PERF and FEV1 will normalize, while the MMEFR remains depressed.
