Review Lectures

Question 1

Compare and contrast the contractile components (structural components) utilized in smooth muscle and skeletal muscle.

Answer 1

They contain all the same components, except smooth muscle does not contain troponin

Myosin heads in smooth muscle face in various directions, allowing for multi-directional contraction

Dense bodies (smooth) = z-discs (skeletal)

Smooth muscle cells can shrink and bulge

Question 2

Compare and contrast the actomyosin regulation of smooth and skeletal muscle contraction.

Answer 2

Skeletal:
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.

Smooth:
Ca2+ comes into cell from ECM (main source is NOT SR), 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.

Question 3

Describe how calcium participates in both smooth muscle mechanical and electrical events.

Answer 3

Ca2+ comes into cell from ECM (main source is NOT SR), 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.

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.

Question 4

List the signs and symptoms, as well as the cause of the signs and symptoms, of Type I and Type II diabetes.

Answer 4

Type I: Can detect autoantibodies many years before onset of disease. Polyuria, thirst, blurred vision, wt loss, weakness, dizzy, sensory nerve dysfunction (paresthiasis), level of consciousness

Type II: High insulin and normal plasma glucose. Metabolic syndrome (see below). Asympto initially. Infections (from elevated glucose), neuropathy (retinal, peripheral), polyuria, thirst, etc, obesity and metabolic syndrome.

Question 5

Predict common therapeutic strategies employed and the rationale for these strategies in treating Type I and Type II diabetes mellitus.

Answer 5

Type I: Diet, patient education, and INSULIN.

Type II: 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.

Question 6

Recognize the acute complications potentially experienced by patients with diabetes mellitus and the general therapeutic approach to addressing these complications.

Answer 6

Hypoglycemia – sx from ANS (tachycardia, sweating, tremors, nausea, hunger), Neurologic sx (confusion, irritable, blurred vision, tired)
Treat w/ glucose or glucagon.

Diabetic 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.

Question 7

Describe flow, velocity of flow and surface area throughout the vascular system.

Answer 7

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.

Question 8

Describe in the form of an equation the relationship between flow, pressure and resistance (Ohm’s Law and Poiseuille’s Law).

Answer 8

Flow=(Pi-Po )/Resistance

Question 9

List the parameters that need to be known in order to calculate total peripheral resistance and the resistance of the pulmonary circuit.

Answer 9

TPR = Pi – Po / CO
Pi=aortic pressure
Po=right atrial pressure

Pulmonary circuit resistance:
Pulmonary artery pressure Left atrial pressure Cardiac output

Question 10

Explain temperature-induced changes in skin blood flow, sweating, shivering, thermogenesis, piloerection, and epinephrine, norepinephrine and thyroxine induced “nonshivering” thermogenesis in terms of nervous control (which location in CNS, division of ANS) and effector receptors (subtype) activated.

Answer 10

-Heat Loss: Anterior hypothalamus activated
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.

General thermoregulatory sweating: sympathetic cholinergic event
Muscarinic receptors are activated on merocrine sweat glands. Anxiety sweating results from sympathetic adrenergic stimulation of a few sweat glands that have alpha one receptors. Apocrine sweat glands which are in the axillary region are regulated by sympathetic adrenergic control.
Muscle tone is inhibited, therefore shivering is inhibited. Inhibition of chemical thermogenesis will occur
-Exposure to cold-mechanisms for heat gain
Posterior hypothalamus is activated. There is cutaneous vasoconstriction with increased sympathetic tone and alpha one activation.
Piloerection, “Goosebumps”-arrector pilli muscles will be activated via alpha one receptors and increased sympathetic tone. These are attached to cutaneous hair follicles
Shivering is mediated by primary motor center for shivering in the posterior hypothalamus.

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.
Thyroid hormones increase the cellular metabolism and heat production.

Question 11

Be able to describe the difference between myelinated and unmyelinated nerves.

Answer 11

a. Where are the voltage-gated Na+ channels?
Myelinated= in the nodes of Ranvier
Unmyelinated= all along the membrane of the nerve

b. Which conducts more rapidly? Why?
Myelinated nerves conduct more rapidly because the action potential can jump from node to node down the axone making the total “distance” of the nerve that must propagate an action potential much shorter. The capacitance is also much lower.

c. Which conducts more efficiently?
Conduction energy efficient since less membrane generates AP’s less Na+ flows into cell so less work for Na+ - K+ pump

Question 12

Be able to describe briefly how the following diseases or toxins affect synaptic transmission. Is the problem pre-synaptic or post-synaptic? Which are autoimmune

Answer 12

myasthenia gravis: autoimmune disease which reduces the number of acetylcholine receptors at the postsynaptic neuromuscular junction.
Eaton-Lambert Syndrome: autoimmune attack on voltage gated Ca++ channels in the terminals of somatic motor nerves.
botulinum toxin: cleave different spots on either synaptic vesicles or presynaptic plasma membrane proteins, which interferes with neurotransmitter release
-bungarotoxin: a peptide from venom of banded krait, irreversibly blocks nAchR.

Question 13

Identify the names and ligands of the main platelet glycoproteins and G protein-coupled receptors (GPCRs) that induce platelet adhesion, activation, and platelet/platelet interaction .

Answer 13

Glycoproteins

• GPIbα: von Willebrand Factor (vWf)
• GPVI: Collagen
• GPIIa/IIIb: Fibrinogen

G protein-coupled receptors

• P2Y12: ADP
• Protease activated receptor (PAR): Thrombin
• Thromboxane A2 receptor: Thromboxane A2

Question 14

Describe the functions of platelet-secreted ADP, serotonin, and thromboxane A2.

Answer 14

ADP: To further activate platelets

Serotonin: To further activate platelets and to cause vasoconstriction

Thromboxane A2: To further activate platelets and cause vasoconstriction

Question 15

Describe the effects of constricting either the afferent or the efferent arteriole on renal blood flow (RBF) and Glomerular Filtration Rate (GFR). How could you increase the glomerular hydrostatic pressure?

Answer 15

Constrict efferent -> GFR increased, RBF decreased

Constrict afferent -> GFR decreased, RBF decreased

Increase glomerular hydrostatic pressure by vasodilating both efferent and afferent

Question 16

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?

Answer 16

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).

Question 17

Know the general organization of the autonomic nervous system and characteristics of autonomic innervation.

Answer 17

Sympathetic division:
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.
Axons of preganglionic neurons exit via the ventral root with axons from somatic motor neurons.
After entering the spinal nerves they travel through the white rami communicantes.

Parasympathetic division:
Cranial outflow-
Consists of preganglionic fibers in oculomotor, vagus, facial, and glossopharyngeal.
Ganglia lie scattered near target organs.
Sacral outflow-
Parasympathetic fibers destined for pelvic and abdominal viscera.

Enteric division:
Collection of nerve plexuses that surround GI, pancreas, and biliary system.
Can function without input from sympathetic or parasympathetic systems

Autonomic system characteristics:
Dual innervation: Most organs receive both sympathetic and parasympathetic innervation.
Only sympathetics: hair, sweat glands, liver, adrenal glands, kidneys, blood vessels

Question 18

know the steps of autonomic transmission, especially the basis for pharmacological intervention at each of these steps: neurotransmitter synthesis, storage, release and termination of action

Answer 18

see your notebook

Question 19

Know the muscles of inspiration and expiration and how they work during the phases of respiration.

Answer 19

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

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

Question 20

Define and list some clinical uses of FVC, FEV1, FEV1/FVC ratio, FEF25-75.

Answer 20

Forced vital capacity (FVC): total volume of air that can be forcibly expired after a maximal inspiration
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
FEV1/FVC: fraction of total FVC that can be expelled in the first second; normal = 0.8
Forced expiratory flow at 25-75% of exhaled VC (FEF25-75): flow rate at 25-75% of exhaled VC

Question 21

Forced vital capacity (FVC): total volume of air that can be forcibly expired after a maximal inspiration
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
FEV1/FVC: fraction of total FVC that can be expelled in the first second; normal = 0.8
Forced expiratory flow at 25-75% of exhaled VC (FEF25-75): flow rate at 25-75% of exhaled VC

Answer 21

Obstructive: both FVC and FEV are decreased, but FEV is decreased more, so the ratio also decreases

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

Question 22

Recognize the different patterns of flow volume curve in typical cases of obstructive lung disease, restrictive lung disease, and upper airway obstruction.

Answer 22

see notebook.

Question 23

Know the main differences between the three most prevalent obstructive lung disorders: asthma, chronic bronchitis and emphysema

Answer 23

see notebook chart.

Question 24

Describe the main pathophysiological features of chronic asthma and understand the corresponding therapeutic options

Answer 24

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).

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.

Question 25

Recognize key pulmonary function test abnormalities in obstructive lung disorders

Answer 25

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.