Final Exam Flashcards
(176 cards)
1
Q
What are the three major functions of respiration?
A
1) Ventilation - breathing, the mechanical process
2) Gas Exchange - occurs between air and blood in the lungs and between the blood and other tissues in the body
3) Oxygen Utilization - by the tissues, in the energy-liberating reactions of cell respiration
2
Q
Describe the pathway of air through the lungs.
A
1) Mouth or nose
2) Pharynx - the cavity behind the palate that receives the content of both oral and nasal passages
3) Larynx - “voice-box,” guards the entrance to the trachea
4) Trachea - “windpipe,” located in the neck in front of the esophagus; a sturdy tube supported by rings of cartilage
5) Primary bronchii - two large air passages that branch off the trachea
6) Terminal bronchioles
7) Respiratory bronchioles
8) Alveolar sacs
3
Q
Differentiate the two types of alveolar cells.
A
Type 1 - compose most of the surface area of the lung; primary gas exchange sites; very thin and very close to the capillaries
Type 2 - secrete pulmonary surfactant, and reabsorb Na+ and H2O preventing buildup in the alveoli
4
Q
What gives alveolar walls their tensile strength, and why is it important?
A
The basement membrane of type I alveolar cells is fused with the basement membrane of the pulmonary capillaries.
Provides alveoli with ability to withstand high stress during exercise, and heavy lung inflation.
5
Q
Describe the general anatomy of the thoracic cavity.
A
- Cavity above the diaphragm
- Contains heart, large blood vessels, trachea, esophagus, thymus, and lungs
- Structures in the middle (lungs, heart) are enveloped by two pleural membranes (outer parietal, inner visceral) which are normally pushed together, but can be brought apart by lung collapse, creating intrapleural space
6
Q
What are the pressures of the relevant lung spaces at inspiration and expiration?
A
Inspiration -
Intrapulmonary = -3
Intrapleural = -6
Transpulmonary = +3
Expiration -
Intrapulmonary = +3
Intrapleural = -3
Transpulmonary = +6
Transpulmonary pressure is always positive, causing lungs to stick to the chest, producing volume change during inspiration.
7
Q
What happens to the pressure in the lungs when you inhale?
A
- As volume of the thoracic cavity increases, intrapleural pressure decreases due to increased opposing forces of lungs and chest wall.
- The decrease in intrapleural pressure maintains the positive transpulmonary pressure necessary to increase lung volume as throacic volume increases.
- As lung volume increases, pressure decreases inside the lungs according to Boyle’s law; negative intrapulmonary pressure creates a gradient for air to enter the lungs.
8
Q
What does lung compliance refer to?
A
The ease with which the lungs can expand under pressure; change in lung volume per change in transpulmonary pressure, ∆V/∆P; greater transpulmonary pressure will cause more or less expansion depending on lung compliance
9
Q
How does pulmonary fibrosis affect lung compliance?
A
Refers to the infiltration of lung tissue with connective scar tissue proteins. This causes the lung to become less distensible, and leads to shortness of breath.
10
Q
What does lung elasticity refer to?
A
The tendency of the lungs/alveoli to return to their initial size after being distended.
The lungs are normally in a state of constant elastic tension, which increases during inspiration; they require elasticity as a driving force for expiration.
11
Q
How do surface tension forces interact with the lungs?
A
A force that acts to resist distension exerted by the fluid in alveoli.
- Water molecules on surface of alveoli are attracted to other water molecules more than to air and thus are pulled together by attractive forces from beneath → force to collapse alveolus, incrs pressure within alveolus
12
Q
What is the law of Laplace?
A
The pressure created by surface tension should be greater in smaller alveoli than in larger ones, implying that, without surfactant, smaller alveoli would collapse and empty their air into larger ones.
P = (2 * T)/r
13
Q
How does surfactant act to decrease surface tension as radius of alveoli decreases?
A
- Made of phospholipids, and hydrophobic surfactant proteins
- Becomes interspersed between water molecules at the water-air interface; reducing H-bonding between water molecules and decreasing surface tension
- Ability of surfactant to decrease surface tension improves as alveoli get smaller during expiration, possibly because the molecules of surfactant become more concentrated as alveoli get smaller.
14
Q
Describe the mechanism of inspiration.
A
1) Diaphragm and external intercostals contract
2) The volume of the thoracic cavity and lung volume incrs
3) Intrapulmonary pressure decreases to about -3mmHg
In forceful inspiration, scalene and sternocleidomastoid muscles also contract, creating a much larger volume increase in the lungs, bringing the intrapulmonary pressure much lower.
15
Q
Describe the mechanism of expiration.
A
1) Diaphragm and external intercostals relax
2) Elastic recoil of lungs occurs
3) Lung volume is decreased
4) Intrapulmonary pressure increases to about +3mmHg
In forceful expiration, the internal intercostals and abdominals contract lowering lung volume much more drastically, and increasing the intrapulmonary pressure much more.
16
Q
What is Dalton’s law of partial pressures?
A
The total pressure is the sum of all of the partial pressures of gases present.
Partial pressure is equal to the percentage of gas present times the total pressure.
17
Q
How would one calculate the PO2 at the alveoli?
A
The atmospheric pressure of O2 is 159 mmHg.
The pressure of water vapor in the lungs is 47mmHg, so the pO2 in the lungs is lower, 150 mmHg.
In the alveoli, O2 is entering from the lungs, and leaving to the capillaries, so pO2 is even lower, 105 mmHg.
18
Q
What is Henry’s Law? How does it apply to respiratory function?
A
The amount of gas dissolved in a fluid depends on:
1) the solubility of the gas in the fluid
2) the temperature of the fluid (more gas dissolves in cold water)
3) the partial pressure of the gas
In the blood, the solubility of O2 and the temperature do not vary significantly. Thus, the concentration of O2 dissolved in plasma depends on partial pressure of O2.
PO2 = [O2]/SO2
19
Q
What is the benefit of breathing 100% oxygen? What is the P02 of 100% oxygen?
A
This wouldn’t significantly effect the oxygen contained in red blood cells, because they are already 97% saturated.
It would increase the concentration of O2 dissolved in the blood, producing a only small change in the oxygen content of the whole blood, because the plasma contains little O2 compared to RBCs.
However, it would increase the rate of delivery of O2 to the tissues because O2 must dissolve in the blood before it can be used by tissues.
The PO2 of 100% O2 is 760 mmHg
20
Q
What is the ventilation/perfusion ratio, and how do the lungs and body compensate to keep it close to 1?
A
The ratio of alveolar ventilation to pulmonary blood flow.
Systemic arterioles:
- dilate in response to low alveolar PO2
- constrict in response to high alveolar PO2
- to bring more blood to tissues when oxygen concentration of blood is low*
Pulmonary arterioles:
- constrict in response to low alveolar PO2
- dilate in response to high alveolar PO2
- to decrease blood flow to arterioles that are inadequately ventilated, preventing mixing of blood from poorly ventilated and well ventilated alveoli, which would lead to lowered blood PO2 through a dilution effect*
21
Q
How does the ventilation/perfusion ratio vary throughout the lung?
A
At base of the lungs:
- gravity makes there be more perfusion
- more lung tissue/expansion of alveoli, so more ventilation
- net - relatively underventilated for blood blow*
At apex of lungs:
- less perfusion due to gravity
- less lung tissue, and so less ventilation
- net - relatively overventilated for blood flow*
As a result of uneven ventilation to perfusion matching, the blood leaving the lungs into the arterial blood stream has a PO2 slightly lower than alveolar air due to diffusion.
22
Q
What is decompression sickness, or “the Bends?”
A
When a person is exposed to high pressure, the partial pressure of nitrogen increases, and therefore, the concentration of nitrogen dissolved in their blood increases.
If they transition slowly back into normal pressure, the nitrogen can diffuse across alveoli, and be expired.
If they transition rapidly back into normal pressure, the nitrogen comes out of solution in bubbles in the blood, which can blood small blood vessels and cause joint and muscle pain.
23
Q
Describe the neural regulation of ventilation.
A
1) Centers in pons send axons to higher order neurons in the rhythmicity centers of the medulla.
2) Medullary neurons innervate phrenic motor nuclei in C3-C6 in the spinal cord through dorsal (excitatory) and ventral (inhibitory) groupings
3) Phrenic motor nuclei innervate phrenic nerves.
4) Phrenic nerves innervate respiratory muscles, and they are either excited or inhibited.
*can also be voluntary, via direct cerebral stimulation of phrenic motor nuclei.
24
Q
What is the role of chemoreceptors in the regulation of ventilation?
A
The automatic control of breathing is influenced by input from chemoreceptors that are sensitive to changes in pH of brain interstitial fluid and cerebrospinal fluid, as well as changes of PCO2, pH, and PO2 of the blood.
25
What are the two types of respiratory chemoreceptors, and how do they influence automatic control of ventilation?
Central chemoreceptors - chemoreceptors in the medulla oblongata; input directly to rhythmicity centers in medulla
Peripheral chemoreceptors - chemoreceptors contained in small nodules in the aorta and carotid arteries
- aortic bodies control breathing through vagus nerve (CN X)
- carotid bodies control breathing through glossopharyngeal nerve (IX)
26
How does ventilation rate affect blood PCO2 and pH?
during hypoventilation: pCO2 increases (hypercapnia), and CO2 combines with water to form carbonic acid, lowering blood pH
during hyperventilation: pCO2 falls (hypocapnia), and pH rises due to excessive elimination of carbonic acid
27
By what mechanism are chemoreceptors stimulated?
Central Chemoreceptors:
- not affected by arterial pCO2 or pH, but CO2 can cross the BBB to lower pH of cerebrospinal fluid
- responsible for 70-80% of the rise in ventilation in response to high pCO2, but a slow/steady-state increase, only if high PCO2 is sustained
Peripheral Chemoreceptors:
- aortic and carotid bodies are stimulated directly by a fall in blood pH
- responsible for an immediate rise in ventilation in response to low pH
28
How is most oxygen carried in the blood?
Bound to hemoglobin.
-each molecule of hemoglobin has:
two alpha chains and two beta chains (proteins)
each polypeptide chain is combined with one heme group
each heme group has one Fe2+, which can combine with one molecule of O2
therefore, one hemoglobin —> four oxygen
-normally, percent oxyhemoglobin saturation is ~97%
29
What is anemia and why is it a problem?
Anemia refers to low hemoglobin concentration in the blood; it's a problem because blood oxygen concentration is dependent on blood hemoglobin concentration.
Often leads to RBCs producing increased amounts of 2,3-DPG, allowing for increased O2 unloading
30
What two factors determine the extend to which oxygen will be loaded or unloaded onto hemoglobin?
1) The PO2 of the environment. High PO2 favors loading.
| 2) The affinity between hemoglobin and oxygen. High affinity favors loading.
31
What is the oxyhemoglobin dissociation curve?
A graphic illustration of the percent oxyhemoglobin saturation at different values of PO2; S-shaped; large amount of oxyhemoglobin remains in the veins at rest (PO2 = 40mmHg) as an oxygen reserve.
Percent oxyhemoglobin dissociation increases by 25% as blood passes from arteries to veins.
32
What is the Bohr effect?
Oxyhemoglobin binding affinity is decreased by low pH and increased by high pH, rightward shift of the curve, indicating greater unloading of oxygen.
*because pH can be decreased by excessive CO2, the Bohr effect provides more O2 to tissues when CO2 output becomes increased due to faster metabolism.
33
How does temperature affect oxyhemoglobin binding affinity?
Temperature increase leads to a rightward shift of the curve (temp decreases bond strength), allowing more oxygen to get to muscles warmed from exercise
34
How does 2,3-DPG affect oxyhemoglobin binding affinity?
2,3-DPG production is normally inhbitied by oxyhemoglobin, so when oxyhemoglobin is low, it is produced.
Binds to deoxyhemoglobin and makes more stable, favoring more unloading of oxygen; a rightward shift of the curve.
35
How is CO2 carried in the blood?
1) As dissolved CO2 in the plasma; ~1/10
2) As carbamino-hemoglobin (attached to an amino acid in hemoglobin); ~1/5
3) As bicarbonate ion, accounting for most of CO2 in the blood
36
How does CO2 lower blood pH?
CO2 combines with water to form carbonic acid.
- spontaneously and slowly in the blood
- catalyzed by carbonic anhydrase in RBCs
*reaction favored by high PCO2 in the systemic capillaries
37
What is the normal pH of blood?
7.35-7.45
38
Describe the chloride shift.
1) In the systemic capillaries, a large amount of carbonic acid is produced due to catalysis by carbonic anhydrase, favoring carbonic acid's dissociation into H+ and bicarbonate.
2) H+ is mostly buffered/trapped by combination with hemoglobin inside cell.
3) Bicarbonate diffuses out into the plasma.
4) Net result is positive charge of the RBC, attracting chloride anions from plasma.
chloride shift: the exchange of chloride anions as blood travels through tissue capillaries
39
Describe the reverse chloride shift.
1) In the pulmonary capillaries, deoxyhemoglobin is converted to oxyhemoglobin, decreasing it’s binding affinity for H+ that it had been buffering.
2) H+ is released within the RBCs, attracting bicarbonate from the plasma; they combine to form carbonic acid.
3) Because pulmonary capillaries have low PCO2, carbonic anhydrase catalyzes the conversion of carbonic acid to CO2 and water vapor, which is eliminated in expired breath.
reverse chloride shift: the conversion of carbonic acid to CO2 and H2O under low PCO2 conditions in the pulmonary capillaries
40
What is the function of the chloride shift and the reverse chloride shift.
To maintain relatively stable concentrations of H+, carbonic acid, and bicarbonate in the blood, and maintain acid-base balance.
41
What are the main mechanisms that regulate the acid-base balance of the blood?
1) lung regulation of [CO2] in the blood
| 2) kidney regulation of [HCO3-] in the blood
42
What is acidosis and how can it come about?
acidosis - a fall in blood pH below 7.35
- respiratory acidosis is caused by hypoventilation that results in increased plasma [CO2]
- metabolic acidosis can result from excessive production of non-volatile acids (ex. ketone bodies in diabetes) OR loss of bicarbonate (ex. due to diarrhea, loss of bicarbonate ion in pancreatic juice)
43
What is alkalosis and how can it come about?
alkalosis - a rise in blood pH above 7.45
- respiratory alkalosis is caused by hyperventilation that results in decreased plasma [CO2]
- metabolic alkalosis can result from too much bicarbonate (ex. intravenous infusion) OR inadequate nonvolatile acids (ex. from excessive vomiting, loss of acid in gastric juice)
44
What is the significance of the Henderson-Hasselbach equation?
The equation used to calculate blood pH given the concentration of bicarbonate and the partial pressure of CO2.
A normal pH is given by a 20 to 1 ratio of bicarbonate to carbon dioxide.
pH = 6.1 + log ([HCO3-]/0.03 PCO2)
45
How does hypo or hyper ventilation lead to pH changes?
In hypoventilation, respiration is insufficient to “blow off” excess CO2; [carbonic acid] becomes excessively high and respiratory acidosis occurs
In hyperventilation, respiration rate is greater than rate of CO2 production; [carbonic acid] becomes excessively high, and raises pH of blood and respiratory alkalosis occurs.
*Also raises pH of cerebrospinal fluid, leading to vasoconstriction —> reduction of blood flow —> dizziness
46
By what two mechanisms does ventilation change during exercise?
Ventilation increases.
Neurogenic - immediate response;
1) sensory nerve activity from exercising limbs may stimulate respiratory muscles via spinal reflexes or brain stem respiratory centers, and/or
2) input from the cerebral cortex may stimulate the brain stem centers to modify ventilation
Humoral (chemical) - ongoing response; rapid/deep ventilation continue after exercise stops.
Although PO2, PCO2, and pH of blood samples of exercising subjects are in resting range, it is proposed that:
1) the PCO2 and pH in the region of the chemoreceptors may be different than values downstream where blood samples were taken, and/or
2) cyclic variation in these values that cannot be detected in blood samples may stimulate chemoreceptors
47
What are the immediate changes observed when an individual moves to high altitude?
Changes in Ventilation (immediate):
decreased arterial PO2 —> carotid bodies —> increase in ventilation —> dcrs PCO2 in blood —> respiratory alkalosis —> increased affinity of hemoglobin for oxygen —> better O2 loading in the lungs
48
What changes might be observed days after an individual moves to high altitude?
The Affinity of Hemoglobin for Oxygen (days):
low oxyhemoglobin —> incrs production 2,3-DPG —> decreased affinity of hemoglobin for O2 —> increased O2 unloading to tissues
49
What changes might be observed weeks after an individual moves to high altitude?
Increased Hemoglobin and RBC Production (weeks):
dcrs tissue O2 concentration (hypoxia) —> kidney cells secrete erythropoietin —> incrs production of hemoglobin and RBCs in bone marrow —> incrs O2 content in the blood
50
What are the major symptoms and physiological causes of acute mountain sickness?
Symptoms: Headache, nausea, dizziness, labored breathing, high BP, hyperventilation
Low arterial PO2 → vasodilation in pia mater → increased blood flow to the head → increased pressure → headache
*hyperventilation is compensatory*
51
How can widespread alveolar hypoxia lead to pulmonary hypertension, and potentially right ventricular failure?
Pulmonary arteries respond to low alveolar PO2 with vasoconstriction, in order to decrease blood flow to arterioles that are inadequately ventilated, preventing mixing of blood from poorly ventilated and well ventilated alveoli, which would lead to lowered blood PO2 through a dilution effect.
The right ventricle has to contract against the pressure of the pulmonary vessels in order to pump blood to the lungs. If there is extreme pulmonary hypertension, the right ventricle won't be able to pump blood as well, and may suffer damage.
52
What is the renal system responsible for regulating?
Through urine formation, the kidneys regulate:
1) blood plasma volume
2) concentration of waste products in the plasma
3) concentration of electrolytes (Na+, K+, and HCO3-) in the plasma
4) plasma pH
53
Describe the gross structure of the kidneys.
Kidneys - paired, kidney bean-shaped, fist-sized, organs that lie on either side of the vertebral column below the diaphragm and liver; urine is produced in them; made up of:
renal cortex - outer region of the kidneys; reddish brownish and granular appearance due to many capillaries and
renal medulla - inner region of the kidneys; striped in appearance due to microscopic tubules and blood vessels; composed of:
8-15 conical renal pyramids separated by renal columns;
each pyramid projects into a small depression, or minor calyx, which join together to form a major calyx, which join together to form the renal pelvis
- urine drains from the kidneys into the renal pelvis and then is channelled from each kidney via long ducts called the ureters
- the ureters undergo peristalsis via pacemaker waves from the renal calyces and pelvis, which also undergo peristalsis
- from the ureters, the urine is deposited into the urinary bladder, a storage sac for urine, which is drained inferiorly through the urethra
54
What is a nephron? What are the two types?
Nephron - the functional unit of the kidney responsible for the formation of urine; more than 1 million per kidney
consist of small tubules and associated small blood vessels; fluid formed by capillary filtration enters the tubules and is modified by transport processes
juxtamedullary nephrons: nephrons that originate in the inner one third of the cortex, longer nephron loops —> ability to concentrate urine
cortical nephrons: nephrons that originate in the outer two thirds of the cortex, more numerous
55
How does blood flow to and through the kidneys?
1) blood enters the kidney through the renal artery
2) divides into the interlobar arteries that pass between the renal pyramids through the renal columns
3) subdivides to arcuate arteries, and then
4) interlobular arteries, and finally into
5) microscopic afferent arterioles, which deliver blood to the glomeruli, which are capillary networks that produce a urinary filtrate that enters the tubules
6) blood remaining in the glomeruli leaves through an efferent arteriole which delivers the blood to the peritubular capillaries surrounding the renal tubules
56
Describe the structures of the four nephron tubules.
glomerular (Bowman’s) capsule - surrounds the glomerulus, located in the renal cortex; contains an inner epithelium around the capillaries, and an outer parietal layer; space between layers is continuous with the lumen of the tubule and receives glomerular filtrate
proximal convoluted tubule - filtrate that enters the glomerular capsule passes through to the PCT; wall consisting of a single layer of cuboidal epithelial cells with millions of microvilli, increasing SA for reabsorption of salt, water, and other molecules back into the blood stream through the peritubular capillaries.
loop of Henle - fluid is carried into the medulla via the descending limb and returned to the cortex via the ascending limb
distal convoluted tubule - fluid passes to DCT following ascending loop of Henle; shorter than the PCT and fewer microvilli; empties into a collecting duct which drains into the medulla, passes through a minor calyx, and is funneled through the renal pelvis and out of the kidney in the ureter.
57
What are the three layers of the glomerular capsule endothelium, and how do they work to allow the filtration of the blood?
1) capillary fenestrae - large enough pores to allow proteins to pass, but surrounded by charges that may serve as a barrier against certain proteins
2) glomerular basement membrane - a layer of collagen IV and proteoglycans immediately outside the capillary endothelium; very thick, restricts rate of fluid flow; impermeable to some proteins
3) visceral layer - composed of podocytes; narrow slits between foot processes allow passage of filtrate through slit diaphragms
* dissolved plasma solutes easily pass through, but most plasma proteins are excluded due to large size and negative charge
58
How does fluid enter the glomerular capsule?
As the blood passes through the glomerular capillaries from the afferent arterial, the hydrostatic pressure of the blood causes ultrafiltrate to form in the glomerular capsule.
Although this force is opposed by the hydrostatic pressure of the glomerular capillaries, and the higher colloid osmotic pressure of the plasma that promotes osmotic return to the capillaries, the net filtration pressure is still positive.
59
What is the GFR and what does it indicate?
The volume of filtrate produced by both kidneys per minute, avg. 115-125 mL/min.
The GFR must be high enough to allow the kidneys to eliminate waste products sufficiently, but low enough as not to cause excessive water loss.
60
How is GFR regulated by the SNS?
SNS activation (via baroreceptors) → vasoconstriction of afferent arteriole → preserves blood volume and diverts blood back to the muscles and heart
61
How is GFR regulated by renal autoregulation?
Afferent arterioles dilate when the MAP falls toward 70mmHg and constrict when the MAP rises above normal.
1) myogenic constriction of the afferent arteriole, due to the ability of smooth muscle to sense and respond to an increase in arterial pressure
2) chemical stimulation of the afferent arteriole, part of tubuloglomerular feedback; increased NaCl and H2O to the distal tubule → release of ATP from macula densa → vasoconstriction of afferent arteriole
- sensor is a group of cells called the macula densa, located in the thick portion of the ascending limb, part of JGA
62
How are salt and water reabsorbed at the proximal tubule?
65% of salt and water is reabsorbed here; occurs regardless of hydration state.
1) Active transport of Na+ out of the lumen through the epithelial cells via Na/K transporters
2) Transport of Na+ out makes the lumen more negative, and Cl- follows Na+ out of the lumen via passive transport
3) Accumulation of NaCl molecules in the interstitial fluid causes water to diffuse out of the tubule via osmosis
63
What are the properties of the ascending limb of the nephron loop?
- thin segment and thick segment, but thick is the important one
- thick segment is not permeable to water, but actively transports Na+ out of the tubule
1) movement of 1Na+ from lumen down gradient into epithelial cells powers the transport of 1K+ and 2Cl- into the lumen
2) Na+ is then actively transported across basal membrane into interstitial fluid via Na+/K+ pumps
3) Cl- follows passively via electrical gradient
4) K+ diffuses passively back into the filtrate, and some diffuses into the interstitial space.
* Filtrate that enters the distal tubule is dilute (hypotonic), while the interstitial fluid in the medulla is concentrated (hypertonic)
64
What are the properties of the descending limb of the nephron loop, and how do they interact with the environment created by the ascending limb?
- impermeable to NaCl, but permeable to water
- because the interstitial fluid is made hypertonic by the action of the ascending limb, water moves out of the descending limb via osmosis
1) the tubular fluid becomes increasingly concentrated (more salty) as the concentration of the interstitial fluid increases
2) transport of Na+ out of the ascending limb increases accordingly —> it’s a cycle
65
Describe the process of countercurrent multiplication.
1) Suppose fluid is isosmotic when it reaches the ascending limb.
2) The thick ascending limb pumps out some NaCl, making the interstitial fluid a bit hypertonic.
3) Due to the hypertonic interstitial fluid, some water leaves the descending limb by osmosis, making filtrate somewhat hypertonic when it reaches the ascending limb.
4) More NaCl is pumped out because more NaCl is present to be utilized by the channels, making the interstitial fluid more hypertonic.
66
What is the purpose of the countercurrent multiplier system?
The main function is to increase the concentration of the interstitial fluid in the renal medulla, compared to in the cortex.
This serves as a driving force for water reabsorption through the collecting ducts, which travel through the medulla to empty urine into the renal pelvis.
67
What are the vasa recta?
Blood vessels that parallel the nephron loops and serve as the major vessels carrying blood in and out of the renal medulla.
68
What properties of the vasa recta lead to countercurrent exchange?
Success of countercurrent multiplier system depends on solutes staying in renal medulla, and water is removed by the blood.
Vasa recta are permeable to water, sodium chloride, and urea due to aquaporins and urea transporters in the vessels
Countercurrent exchange begins in the descending vessel, when solutes from the interstitial fluid diffuse in and water leaves, and then continues in the ascending level, when solutes diffuse back out and water osmotes in, maintaining the hypertonicity of the interstitial fluid.
This occurs because at each level of the medulla, the concentration of solutes is higher in the interstitial than the descending vessels, and lower in the interstitial than the ascending vessels.
69
How does urea contribute to maintaining the hypertonicity of the renal medulla interstitial fluid?
* Countercurrent multiplication mostly works where there is thick ascending limbs, but the deepest portions of the medulla only have thin ascending limbs. SO:
1) Urea diffuses out of the inner collecting duct (in the renal medulla) into the interstitial fluid.
2) It can then pass into the ascending limb of the loop of Henle, so it recirculates in the interstitial fluid of the medulla.
3) The urea and NaCl in the renal medulla make it very hypertonic, so water leaves the collecting duct by osmosis.
70
What are the properties of the collecting ducts?
- Permeable to water, but impermeable to NaCl
- As ducts pass through the hypertonic interstitial fluid of the renal medulla, water leaves through osmosis and is transported via capillaries to systemic circulation
- Rate of osmosis across collecting duct walls can be adjusted by regulation of # aquaporins
71
How does ADH effect the collecting ducts?
1) in response to increase in plasma osmolality, posterior pituitary secretes antidiuretic hormone
2) ADH binds to membrane receptors in the collecting duct, and stimulates the production of cAMP
3) cAMP causes vesicles containing aquaporins to move from the golgi apparatus and fuse with the membrane of the collecting duct
4) This allows for a higher rate of osmosis and more reabsorption of water
72
To what does renal plasma clearance refer, and what are the two general mechanism by which it happens?
As blood moves through the kidneys, the blood plasma is cleared of particular solutes (excess ions, metabolic waste products) which are excreted in the urine.
1) Filtration with no reabsorption
2) Secretion from the peritubular capillaries into the tubules.
73
What is the action of OATs and OCTs?
Xenobiotics are regularly eliminated from the blood plasma and transported across the basolateral membrane of the proximal tubule to be excreted in the urine.
They are transported by OATS and OCTs, which are sodium independent transporters in the basolateral membrane of the proximal tubule epithelium that transport exogenous anions and cations into the filtrate.
74
What is renal clearance of PAH indicative of?
Para-aminohippuric acid is a compound that is removed from the blood in a single circulation through the kidneys because it is secreted at a high rate; clearance used as a measure of renal blood flow.
75
What is inulin, and why is it useful?
Inulin is a compound that is neither secreted or reabsorbed, and so its excretion rate is equal to the glomerular filtration rate.
76
How is renal plasma clearance calculated?
RPC = (urine concentration * urine flow)/plasma concentration
77
Substance W has a clearance greater than zero, but less than that of inulin. What can you conclude about substance W?
Substance W is filtered, but partially reabsorbed.
78
What is the formula for GFR?
GFR = (urine concentration * urine flow)/plasma concentration
79
What is the relationship between GFR and RPC?
The RPC of a substance that is filtered and secreted is greater than the GFR.
80
How is glucose reabsorbed by the kidney?
Glucose is filtered by the glomeruli but is not present in the urine under normal conditions due to:
1) Cotransport of glucose and amino acids from the lumen across the apical membrane of the proximal tubule epithelium, coupled with sodium, which is moving down its gradient due to Na+/K+ channel in the basolateral membrane.
2) Glucose then diffuses across the basolateral membrane via a specialized membrane channel, and is reabsorbed into the peritubular capillaries which are permeable
81
How does aldosterone act to maintain plasma electrolyte balance?
* While 90% of filtered Na+ and K+ is reabsorbed in the proximal tubule and nephron loop, the remaining 10% is subject to hormonal regulation in the late distal tubule and collecting ducts.
1) aldosterone (released from adrenal cortex in response to high potassium or low sodium or low blood volume and pressure) stimulates activity of Na+/K+ pumps
2) Na+/K+ pumps in the basolateral membrane of the late distal tube and cortical collecting ducts move Na+ into the interstitial fluid and then the blood, and promote secretion of K+ from the blood into the filtrate
3) these channels stimulate further outflux of sodium across the apical membrane and into the cytoplasm through sodium channels via electrochemical gradient, and chloride is also reabsorbed, passively
82
How is K+ handled by the kidney?
Most of it is reabsorbed in the proximal tubule. 10% is subject to aldosterone regulation of Na+/K+ channels in the cortical collecting duct.
Also, independent of aldosterone, rise in blood K+ causes the insertion of K+ channels in the basolateral membrane of the cortical collecting duct, such that K+ diffuses across apical membrane due to potential diff. created by reabsorption of Na+
83
What might cause hyper- and hypokalemia?
High or low plasma potassium.
Hyperkalemia may be due to adrenal insufficiency leading to problems w/aldosterone release.
Hypokalemia may be due to diuretics, vomiting, metabolic alkalosis, or excessive aldosterone secretion.
84
How specifically is aldosterone secretion regulated?
- a rise in plasma K+ concentration depolarizes aldosterone-secreting cells in the adrenal cortex —> aldosterone secretion
- a fall in plasma Na+ concentration promotes aldosterone secretion indirectly via effect of low BV on renin-angiotensin-aldosterone system
85
What is the JGA?
The juxtaglomerular apparatus is the region in each nephron where the afferent arteriole meets the thick ascending limb of the nephron loop.
Contains granular cells that secrete renin into the blood.
86
How does renin affect blood volume and blood pressure?
Renin catalyzes conversion of angiotensinogen to angiotensin I which is converted to angiotensin II in the lungs by ACE.
Angiotensin II is responsible for:
1) stimulating aldosterone secretion from the adrenal cortex
2) stimulating vasoconstriction of afferent and efferent arterioles leading to dcrs GFR and sodium excretion
87
How is renin secretion regulated?
low dietary NaCl → dcrs plasma osmolality → dcrs ADH → dcrs water reabsorption → dcrs BV
Low BV → Low BP → dcrs renal blood flow → renin secretion through:
1) Granular cells act as baroreceptors, less pressure on them leads to renin secretion.
2) SNS activation of B-adrenergic receptors in the granular cells during the baroreceptor reflex.
88
How does the macula densa contribute to regulation of renin secretion?
When the macula densa senses high Na+ in the blood and filtrate via its Na-K-2Cl transporters in the proximal tubule, it:
1) releases ATP stim. afferent arterial to constrict (previously learned)
2) signals granular cells to stop renin secretion, leading to less Na+ reabsorption.
89
How does urine become acidified?
Bicarbonate is reabsorbed and H+ is secreted.
90
What is the mechanism of reabsorption of bicarbonate in the proximal tubule?
1) Na+/H+ antiport secondary active transport in the apical membrane brings H+ into the lumen of the proximal tubule in exchange for Na+
2) H+ reacts with tubular bicarbonate to form carbonic acid
3) carbonic anhydrase in the lumen catalyzes the dissociation of carbonic acid into H2O and CO2
4) CO2 diffuses across the apical membrane as concentration increases
5) In the epithelial cell, carbonic acid catalyzes the reaction in which CO2 and H2O form carbonic acid
6) Carbonic acid then dissociates to form H+ and bicarbonate, and the bicarbonate diffuses across the basolateral membrane into the interstitial fluid
* because apical membrane is impermeable to bicarbonate
91
What is the mechanism of H+ secretion in the distal tubule?
H+ excretion is promoted by H+ ATP-ase pumps in the distal tubule apical membrane, which secrete H+ into the filtrate.
92
How does the body secrete enough H+ in the urine to compensate for acidosis without making the urine excessively acidic?
Urinary buffers!
Ammonium and phosphate serve as buffers:
phosphate —> from filtration
ammonia —> from deamination of glutamine; increased production during acidosis; travels through nephron loop and becomes concentrated in the interstitial fluid, promoting diffusion into collecting ducts
93
What is the basic model of an endocrine system?
1) Glands secrete hormones
2) Hormones interact with target cells
3) Receptors in cells are specific to the hormone.
94
What are the four basic classes of hormones?
Amines - Hormones derived from amino acids tyrosine and tryptophan; secreted from adrenal medulla, thyroid, and pineal glands
Polypeptides and proteins - Hormones that are composed of amino acid chains; ADH, Insulin
Glycoproteins - Consist of a protein bound to one or more carbohydrate groups; FSH, LH
Steroids - Derived from cholesterol after an enzyme cleaves off the side chain attached to the five-carbon “D” ring; testosterone, estradiol, progesterone, cortisol
95
Which hormones are lipophilic? What does this mean functionally?
Steroids and thyroid hormone are lipophilic, or lipid-soluble, meaning they can pass through the cell membrane.
96
What three major factors influence hormonal action?
1) Concentration - dependent on rate of secretion, and half-life of the hormone in the blood
2) Time/Frequency of Exposure - synergistic, permissive, and antagonistic effects
3) Negative/Positive feedback systems - priming effects of more receptors following exposure to a small amount of hormone, desensitization/downregulation following prolonged exposure
97
Why are most hormones secreted in a pulsatile fashion?
In order to avoid prolonged high levels of exposure and subsequent desensitization of target cells via downregulation of receptors.
98
Describe the mechanism of steroid hormone action.
1) Steroid hormones, transported bound to carrier proteins in the plasma, dissociate and pass through the plasma membrane of target cells
2) The steroid hormone binds to receptors, which may be in the cytoplasm
3) The hormone-bound receptor translocates to the nucleus, where it binds to DNA (hormone-response element)
4) This stimulates genetic transcription, resulting in new mRNA synthesis
* Further regulated by coactivators and corepressors.
5) The newly formed mRNA codes for production of new proteins
6) Proteins produce the hormonal effects in the target cell
99
Describe the mechanism of thyroid hormone action.
1) Thyroxine (T4) is carried to the target cell bound to a carrier protein, and dissociates to pass through the plasma membrane of the target cell
2) In the cytoplasm, T4 is converted to T3
3) T3 uses binding proteins to enter the nucleus
4) Thyroid hormone receptor proteins and 9-cis-retinoic acid receptor proteins are bound to DNA, forming a heterodimer
5) When 9-cis-retinoic acid and T3 bind to receptor proteins, the synthesis of new mRNA is stimulated via degradation of corepressors and recruiting of coactivators
6) The newly formed mRNA codes for production of new proteins
7) Proteins produce the hormonal effects in the target cell
100
Which hormones use second-messenger mechanisms of action?
Catecholemines, polypeptides, and glycoproteins are not lipid soluble, and therefore bind to membrane receptor proteins which activate second messengers within the cell.
101
What are the three types of second-messenger systems?
1) Adenylate Cyclase/Guanylate Cyclase - epi and norepi to beta receptors
2) Phospholipase C - epi to alpha receptors
3) Tyrosine Kinase - insulin
102
Describe the mechanism of action of insulin.
1) Two half receptors form a dimer in the cell membrane prior to insulin binding
2) Insulin binding causes autophosphorylation of receptor
3) Active tyrosine kinase of receptor phosphorylates signaling molecule
4) Active signaling molecule causes cascade of effects, including glucose uptake and anabolic reactions.
103
Describe the general mechanism of action of G-protein extracellular mechanisms of action.
1) The hormone binds to its receptor in the plasma membrane of the target cell
2) This causes the dissociation of G-proteins, allowing a free alpha-subunit to activate adenylate-cyclase
3) This enzyme catalyzes the formation of cAMP
cAMP removes regulatory subunit from protein kinase
4) Active protein kinase phosphorylates other enzyme proteins, activating or inactivating specific enzymes and thereby producing the hormonal effects on the target cell
104
Describe the general structure of the pituitary gland.
-pea-sized gland inferior to the hypothalamus; divided into two lobes with different embryonic origins:
anterior lobe (adenohypophysis) - derived from epithelial tissue that migrates upward from the mouth; local cell bodies
posterior lobe (neurohypophysis) - derived from neural tissue; cell bodies are hypothalamic neurons
105
What hormones are secreted by the anterior pituitary?
tropic hormones (tropins); high concentrations cause target organs to hypertrophy, while low concentrations cause target organs to atrophy —> health of organs depends on adequate stimulation by anterior pituitary hormones;
These include: GH, TSH, ACTH, FSH, LH, PRL, and MSH
106
Describe the regulatory and functional aspects of the anterior pituitary hormones.
growth hormone - stimulated by GHRH, inhibited by somatostatin; promotes movement of amino acids into cells and the incorporation of these amino acids into proteins, promoting overall tissue and organ growth, as well as increased blood glucose; cartilage and bone growth result from somatomedin produced in the liver under GH stim
thyroid-stimulating hormone - stimulated by TRH, inhibited by thyroid hormones; promotes secretion of thyroid hormones (thyroxine, T3 and T4) from the thyroid
adrenocorticotropic hormone - stimulated by CRH, inhibited by glucocorticoids; stimulates secretion of glucocorticoids from the adrenal cortex
follicle-stimulating hormone - stimulated by GnRH, inhibited by sex steroids and inhibin; promotes gamete production in males and female, and stimulates estrogen production in females
lutenizing hormone - stimulated by GnRH, inhibited by sex steroids; stimulates 1) sex hormone secretion and ovulation and corpus lute formation in females, and 2) testosterone secretion in males
prolactin - inhibited by PIH (dopamine); promotes milk production in lactating females; additional actions in regulating gonadotropins in males, and acts on kidneys to help regulate electrolyte and water balance
melanocyte stmulating hormone - promotes darkening of the skin; derived from prohormone POMC
107
What hormones are secreted by the posterior pituitary? Describe their functions?
1) antidiuretic hormone (ADH) - promotes water retention in the kidneys through the stimulation of aquaporins in the late distal tubule and cortical collecting ducts; also leads to vasoconstriction, but less important
2) oxytocin - stimulates contractions of the uterus during childbirth, contractions of the mammary gland alveoli and ducts resulting in milk-ejection in lactating women; rise seen in men during ejaculation but unclear significance
108
Describe the mechanism of hypothalamic control of the posterior pituitary.
- ADH and oxytocin are produced in neuronal cell bodies in the supraoptic and paraventricular nuclei in the hypothalamus
- they are then transported along the hypothalamic-hypophyseal tract to the posterior pituitary for storage
- they are released in response to neuroendocrine reflexes
* mechanical stimulus of suckling acts on hypothalamus to stimulate secretion of oxytocin*
* a rise in plasma osmolality stimulates an increased frequency of APs in the neurons that produce ADH, leading to larger release of ADH; can also be inhibited by sensory input from atrial baroreceptors*
109
Describe the mechanism of hypothalamic control of the anterior pituitary.
- Occurs through the action of inhibiting and releasing hormones
- Inhibiting and releasing hormones are produced by neurons in the hypothalamus, and transported to axon endings in the basal portion of the hypothalamus, a region known as the median eminence
- The median eminence has capillaries that are drained into the stalk of the pituitary by venules, and the stalk then drains into another capillary bed in the anterior pituitary
- This is referred to as the hypothalamo-hypophyseal portal system
110
Describe the basic structure of the adrenal glands.
- Paired organs that cap the superior borders of the kidneys
- Each adrenal has an outer cortex and inner medulla, derived from different embryonic tissues
*adrenal medulla - secretes catecholamines (mainly Epi, but some NorEpi) into the blood in response to innervation from preganglionic sympathetic axons; complements the SNS fight or flight response
* adrenal cortex - secretes steroid hormones that participate in regulation of mineral and energy balance; has three layers:
1) zona glomerulosa (outer), 2) zona fasciculata (middle), 3) zona reticularis (inner)
111
Describe the hormones secreted by each layer of the adrenal cortex.
aldosterone - secreted by the zona glomerulosa; stim kidneys to retain Na+ and water while excreting K+; incrs blood volume and pressure and regulate electrolyte balance
cortisol - secreted by the zona fasciculata in response to stimulation by ACTH; effects include 1) stimulation of protein degradation, 2) stimulation of gluconeogenesis and inhibition of glucose utilization to raise blood glucose, 3) stimulation of lipolysis and consequent release of fatty acids into the blood, and 4) inhibits inflammation, stimulates cytokines
adrenal androgens - secreted by the zona reticularis; weak androgens that supplement sex steroids secreted by the gonads; ex. DHEA
112
Describe the pathway of the HPA axis.
1) Stress is detected by higher brain centers which act on the hypothalamus to stimulate release of CRH into the hypothalamo-hypophyseal portal system
2) CRH acts on anterior pituitary to release ACTH into the systemic blood flow
3) ACTH acts on the adrenal cortices to release steroid hormones, particularly cortisol, leading to stress response
4) Cortisol inhibits the adrenal glands and the paraventricular nucleus in the hypothalamus; inhibits hippocampus in chronic concentrations
113
Describe the basic structure of the thyroid glands.
- Located just below the larynx, two lobes on either side of the trachea are connected anteriorly via a mass of tissue called the isthmus
- Contains thyroid follicles, which are numerous spherical hollow sacs lined with simple cuboidal epithelium; contain protein-rich fluid colloid in the middle
- Epithelium of follicles is composed of follicular cells; these synthesize principle thyroid hormone thyroxine.
114
Describe the mechanism by which thyroxine is produced.
1) Thyroid follicles actively intake iodide ions from the blood, and secrete it into the colloid.
2) In the colloid, iodide is oxidized and attached to tyrosine within the polypeptide chain of thyroglobulin
- attachment of one iodine produces monoiodotyrosine
- attachment of two iodines produces diiodotyrosine
3) Enzymes couple MIT and DIT together producing T3 and T4, still attached to thyroglobulin
4) Upon stimulation by TRH, follicular cells take up some colloid, and hydrolyze T3 and T4 from the thyroglobulin, releasing free T3 and T4 into the blood
115
Describe the effects of thyroxine.
- stimulates protein synthesis
- promotes maturation of the nervous system
- increases the rate of cell respiration in most bodily tissues
OVERALL: elevates the basal metabolic rate - the rate of calorie expenditure by the body at rest
116
Describe the action of the pineal gland as an endocrine tissue.
- regulated by SCN, secretes melatonin in response to stimulation by sympathetic axons originating in the superior cervical ganglion
light → melanopsin in retinal ganglion cells → retinohypothalamic tract → SCN → inhibits melatonin from the pineal gland
117
Describe the action of the adipose tissue as an endocrine tissue.
secretes regulatory molecules called adipokines into the blood, in order to regulate hunger, metabolism, insulin secretion, inflammation and immunity, angiogenesis
118
How does endocrine action of adipose tissue change when an individual is obese?
Secretion of adipokine that attracts monocytes that can turn into macrophages
-macrophages secrete TNF-alpha, reducing ability of skeletal muscles to remove glucose from the blood in response to insulin
Increased secretion of leptin (secreted in proportion to stored fat)
- contributes to reduced insulin sensitivity
- acts on the hypothalamus to regulate appetite and help the body maintain its percent fat storage
Decreased secretion of adiponectin
- a molecule which normally acts to stimulate glucose utilization and fatty acid oxidation in muscle cells
119
What are three ways that one might categorize sensory receptors?
1) By stimulus type
2) By sensory info origin (exernal/internal)
3) By sensory info type (proprioceptors, cutaneous receptors, special senses)
120
Describe the types of sensors based on their stimulus type.
chemoreceptors - sense chemical stimuli in the environment or the blood; ex. taste buds, olfactory epithelium
photoreceptors - sense light of different wavelengths; ex. rods and cones in the eyes
thermoreceptors - respond to heat or lack of heat
mechanoreceptors - stimulated by technical deformation of the receptor cell membrane; ex. touch and pressure receptors in the skin, hair cells in the ear
nociceptors - pain receptors that depolarize in response to stimuli that accompany tissue damage; ex. high heat or pressure, acid, abnormal quantities of chemicals
121
What is sensory adaptation, and how do different types of receptors allow or disallow it?
The ability to stop paying attention to constant stimuli; provided by phasic receptors.
Phasic receptors are receptors that respond to a burst of activity when a stimulus is first applied, but then quickly decrease their firing rate if the stimulus is maintained; provide on/off information about a stimulus.
As opposed to tonic receptors, that maintain constant firing as long as they are stimulated; ex. nociceptors.
122
Describe the mechanism by which sensory neurons fire.
In response to the adequate stimulus, there are graded depolarizations of sensory nerve endings, proportional to stimulus size, that serve to generate APs in response to sensory stimulation.
* The frequency of APs is proportional to the magnitude of the generator potentials
* The number of APs is proportional to intensity perceived
123
What are the different cutaneous sensations?
touch, pressure, heat, and pain; mediated by the dendritic endings of different sensory neurons
124
What are the different types of sensory nerve endings in the skin? What do they detect?
free nerve endings - unmyelinated dendritic endings of sensory nerves that detect light touch, heat, cold, and pain; located around the hair follicles, throughout the skin
Merkel’s discs - expanded dendritic endings associated with 50-70 specialized cells that detect sustained touch and indented depth (slow adapting); located at the base of the epidermis, sometimes near hairs
Ruffini endings - enlarged dendritic endings with open, elongated capsules that detect skin stretch; slow adapting; located deep in the dermis, and hypodermis
Meissner’s corpuscles - dendrites encapsulated in connective tissue that detect changes in texture and slow vibrations; located in the upper dermis
Pacinian corpuscles - dendrites encapsulated by concentric lamellae of connective tissue structures that detect deep pressure and fast vibrations; fast adapting; located deep in the dermis
125
What makes nociceptors multimodal?
They are able to respond to a variety of stimuli and perceive it as pain. These stimuli include:
- mechanical stimuli that causes cell damage —> partly through ATP released from damaged cells
- acid, as the local pH falls during inflammation —> acid-sensing ion channels in nociceptors
- histamines, serotonin, and prostaglandins released by injured cells
126
What are the two neural pathways for pain signals?
1) first sensing of pain is due to sensory input transported by the large, heavily myelinated dorsal column system
2) sustained, dull pain is due to sensory input transported by unmyelinated, smaller fibers in the dorsolateral pathway
127
What are TRP channels? What sensory function do they provide?
Transient receptor potential channels. Generally, these are ion channels that respond to particular chemicals or hot and cold temperatures.
Capsaicin receptors - receptor/ion channel proteins (TRP) in the membrane of sensory dendrites that open in response to high temp or capsaicin, allowing Ca++ and Na+ to diffuse into the neuron, producing depolarization; resulting APs are sent to the CNS and perceived as heat and pain
Cold/Menthol receptors - a membrane ion channel (TRP channel) in sensory neurons that responds to menthol and to cold by opening, allowing Ca++ and Na+ to diffuse into the cell, producing depolarization; resulting APs are perceived as cold
128
What do itch receptors respond to?
Acute itch - histamine, can be treated with antihistamines
| Chronic itch - not histamine, other things that cannot be treated with antihistamines
129
What does the labeled line theory tell us?
Somatesthetic information from the an area of the body projects to a specific area of the somatosensory cortex
Thus, referred pain can occur, due to visceral sensory and somatic sensory neurons can synapse on the same interneurons in the spinal cord; can cause pain in the arm or chest during cardiac distress (angina)
130
What is lateral inhibition?
Sensory neurons whose receptive fields are stimulated most strongly by a stimulus inhibit, via interneurons that pass laterally within the CNS, the sensory neurons that serve neighboring receptive fields.
This leads to sharp sensations/localization of sensation on the body, as opposed to fuzzy sensations due to partial stimulation of the surrounding areas.
131
How do receptive fields influence two-point discrimination?
Receptive fields are determined by the density of sensory receptor neurons in a particular area. The more dense the receptors, the better the ability to distinguish between two points. This is because each sensory cell projects to a particular area in the motor homunculus, and touch can stimulate one or many sensory cells.
132
Describe the basic structure of taste buds.
Taste buds have 50-150 chemoreceptors/neuroepithelial cells (epithelial cells modified to release neurotransmitters) each.
133
How is taste information carried to the brain?
Taste info is transmitted from taste buds to medulla via facial nerve and glossopharyngeal nerve, then to thalamus, then to gustatory cortex in insula and to somatosensory cortex.
134
What are the mechanisms by which each taste is detected?
Each taste cell is sensitive to only one category of taste, although any part of the tongue can detect any taste
Salty - sodium and other cations pass through ion channels in sensitive taste cells —> opens Ca++ channels —> depolarization
Sour - H+ passes through ion channels in sensitive taste cells —> opens Ca++ channels —> depolarization
Sweet - Sugar binds to G-protein in membrane of sensitive taste cell, which activates a second messenger to close K+ channels —> depolarization
Umami - Amino Acids bind to G-protein in membrane of sensitive taste cell, which activates a second messenger to close K+ channels —> depolarization
Bitter - Quinine binds to G-protein in membrane of sensitive taste cell, which activates a second messenger to stimulate Ca++ release from endoplasmic reticulum —> depolarization
135
What cells are present in the olfactory epithelium?
- receptor cells (bipolar neurons)
- supporting cells - epithelial cells rich in enzymes that oxidize hydrophobic volatile odorants, making them less lipid-soluble and less able to penetrate membranes and enter the brain
- basal stem cells - generate new receptor cells every one to two months to replace neurons damaged by environment
136
How are we able to smell so many different scents?
Each neuron (of which there are 380) expresses only one type of receptor protein and its axon conveys information only about the specific operant molecule that stimulated the neuron; humans can detect so many different odors because of differential patterns of activation
137
Describe the mechanism of olfactory transduction.
1) Each bipolar sensory neuron has one dendrite projecting into the nasal cavity, where it terminated in a knob containing cilia; the plasma membrane covering the cilia contains receptor proteins that bind to odorant molecules
2) Each olfactory receptor is coupled to many G-proteins, which dissociate upon binding of an odorant.
3) The alpha subunit of the G-proteins activates adenylate cyclase, which catalyzes the production of cAMP
4) cAMP acts as a second messenger and opens Na+ and Ca++ channels, leading to depolarization
5) Axons of receptor neurons in the olfactory epithelium project through holes in the cribriform plate and synapse with neurons in the olfactory bulb in the cerebral cortex in glomeruli
6) each glomerulus receives input from only one type of receptor
7) Secondary neurons known as tufted cells and mitral cells transmit impulses from the olfactory bulb to the olfactory cortex in the frontal and medial temporal lobes
8) Interconnections between olfactory cortex and amygdala and hippocampus via the piriform cortex may account for the strength of olfactory memories.
138
Describe the structure and function of the otolith organs.
Utricle and Saccule - A pair of large chambers near the center of the vestibular labyrinth; provides information about head orientation and linear acceleration.
Each contains a vestibular macula, containing hair cells; hair cells extend into a gelatinous cap encrusted by otolith particles, which have a higher density than surrounding fluid (endolymph), and serve to increase the mass of the membrane, resulting in more inertia.
In utricle, the vestibular macula is arranged horizontally, so detects horizontal acceleration.
In saccule, the vestibular macula is arranged vertically, so detects vertical acceleration.
139
Describe the mechanism of otolith organs.
1) Angle of head changes
2) Force exerted on otoliths
3) Force exerted on gel cap.
4) Cap moves
5) Hair cells move.
6) Bending toward the kinocillium depolarizes, away from kinocillium hyperpolarizes
7) Neurotransmitter released on vestibular/cochlear nerve cells (cranial nerve VIII)
140
Describe the structure and function of the semicircular canals.
Three canals, filled with jelly-like endolymph; detect angular acceleration (generated by sudden rotational movement like turning one’s head)
anterior - somersault
posterior - cartwheel
horizontal - spinning around long axis of the body
141
Describe the mechanism of the semicircular canals.
1) Hair cells (cilia) are embedded in the base of the structure, and extend into a gel mass called the cupula.
2) Force by the movement of the endolymph moves the cupola and bows the cilia, exciting or inhibiting the hair cell.
3) Neurotransmitter released on vestibular/cochlear nerve cells (cranial nerve VIII).
142
How does the vestibular system send signals to the brain?
1) Vestibulocochlear nerve (VIII)
2) Cerebellum and Vestibular Nuclei (in medulla)
3) Vestibular Nuclei to Oculomotor center of brain stem, and the spinal cord
4) control eye movements, and movements of head, neck, and limbs to maintain balance and “track” the visual field during rotation
5) Also to cerebral cortex via thalamus
143
Describe the structure and function of the outer ear.
- sound waves are funneled into the pinna and through the ear canal causing small vibrations of the tympanic membrane
pinna: “wing,” the ear we see; helps locate, capture, focus and filter the source of sounds; “hills and valleys” of the pinna enhance reception of sound from 2,000-5,000 Hz; a range important for human speech.
external auditory meatus: “ear canal”
144
Describe the structure and function of the middle ear.
- the cavity between the tympanic membrane and the cochlea
- Enhances and focuses vibration
tympanic membrane (eardrum): Vibrates at same frequency of sound wave
middle-ear ossicles: malleus (hammer), incus (anvil), stapes (stirrup); malleus is attached to tympanic membrane allowing for transfer of vibration onto the oval window of the cochlea, which is attached to the stapes
145
What is the advantage to having three ear bones? Are there mechanisms that prevent ear damage related to this?
if the sound is too intense, they may buckle, preventing damage to the ear.
Additionally, the stapedius muscle is attached to the neck of the stapes, and contracts in response to sound that could cause damage to the ear, dampening the movements of the stapes against the oval window.
146
Describe the structure and function of the inner ear.
Cochlea - a snail shell shaped organ the size of a pea that composes the inner ear; converts vibration into neural activity
cochlear chambers - within the cochlea, include the scala vestibuli (upper, perilymph), scala tympani (lower, perilymph), scala media or cochlear duct (middle, endolymph)
*the perilymph in scala vestibuli and tympani is continuous, due to a small space between the cochlear duct and the wall of the cochlea, the helicotrema
147
Describe the mechanism by which vibration is transmitted from the oval window to the round window of the cochlear duct.
1) Vibration of the oval window displaces perilymph in the scala vestibuli
2) These pressure waves transfer to the scala tympani
3) Waves travel to the base of the cochlea where they displace the round window
4) *as frequency of sound waves increases, waves may also be transmitted through the vestibular membrane separating upper and middle chambers, and the basilar membrane, separating the middle and lower chambers
148
Describe the mechanism of auditory transduction.
1) Oval window depresses perilymph fluid in cochlea
2) Fluid set in motion.
3) Vibration moves basilar membrane.
4) Shearing force is creates between basilar membrane and
tectorial membrane
5) The stereocilia bend, opening K+ channels in the plasma membrane covering the tops of the stereocilia.
6) K+ channels face endolymph, which has a high concentration of K+
7) The endolymph of the cochlea has a very high positive potential
8) K+ moves passively down its electrochemical gradient into the hair cells, depolarizing them.
9) Hair cells release glutamate, which stimulates sensory neurons of cranial nerve VIII
10) K+ then leaves the hair cell into low K+ scala tympani perilymph through channels in the basal surface
11) Action potential generated in axons of the auditory nerve (Cranial nerve VIII (the auditory-vestibular nerve))
149
How is pitch discrimination accomplished?
Vibration of the basilar membrane is indicative of pitch; low frequency sounds (500 Hz) cause peak vibrations toward the apex of the cochlea, while high frequency sounds (20,000 Hz) cause maximum vibrations closer to the stapes.
*Hair cells located in areas where pitch displacement is greatest will be stimulated more than neurons in other regions of the basilar membrane.
150
What is the neural pathway for hearing?
1) Cochlear nucleus (ipsilateral input aka on each side) →
2) Directly to the Inferior colliculus (auditory center of midbrain) OR to the superior olivary nucleus (binaural processing) and then through the lateral lemniscus of the inferior colliculus→
3) Medial Geniculate Nucleus (MGN) in the thalamus →
4) Auditory Cortex (A1) in the Temporal lobe
151
What does tonotopic organization refer to?
In the cochlear nucleus, different regions represent different pitches; separation of neurons by pitch is preserved in the auditory cortex.
152
How do we detect intensity of sound? How do interaural differences help us localize sound?
- loudness is determined by frequency of APs
- can be used to localize a sound if APs are more frequent in one ear than the other
- sound localization is further aided by interaural time difference
153
How many muscles are associated with the eye?
-6 ocular muscles in 3 antagonists pairs; adjust the position of the eye
superior/inferior rectus - anterior top and bottom of eyeball
- superior - upward
- inferior - downward
superior/inferior oblique - posterior top and bottom of eyeball
- superior - downward and outward
- inferior - upward and outward
medial/lateral rectus - sides of eyeball
- medial - inward
- lateral - outward
- ciliary muscles; adjust the lens shape
- other muscles adjust pupil size
154
What happens to your eyes when you feel dizzy?
Upon prolonged rotation, endolymph moves with hair cells; when spinning stops, endolymph moves in opposite direction → dizzy feeling in the opposite direction.
155
How do you fix your gaze on something when it is moving?
This is accommodation, or the ability of the eyes to keep an image focused on the retina as the distance between the eyes and the object varies.
It is allowed by the contraction of the ciliary muscle that varies the aperture of the lens.
156
Which CNs are associated with the eyes?
```
CN II (optic nerve)
CN III, IV, and V (Oculomotor, Trochlear, Abducent)
CN V (trigemental)
CN VI (facial)
```
157
How is 3-D vision accomplished?
Retinal disparity is the space between the eyes that allows binocular vision to create depth perception; both eyes converge on a box but due to retinal disparity, the angle of viewing is slightly different for each eye.
158
What is the neural pathway of vision?
1) Light (photons) →
2) Receptors in the back of the eye (cones and rods) →
3) Bipolar cells closer to the center of the eye →
4) Ganglion cells even closer to the center of the eye →
5) Optic nerve (ganglion cell axons) →
6) Optic chasm (signals cross) →
7) Optic tract and superior colliculus→
8) Lateral geniculate nucleus of the thalamus (LGN) →
9) Visual cortex (V1); Light from the right ends up in the left visual field and visa versa.
159
What determines sex of an embryo?
The Y chromosome contains a gene called SRY that codes for a protein called TDF, which leads to the development of the seminiferous tubules, which produce sperm.
160
What cells are present in the seminiferous tubules in embryo?
germinal cells - will eventually become sperm
Sertoli cells - non germinal cells
Leydig cells (interstitial) - endocrine tissue of the testes; secrete large amounts of testosterone (beginning at 8 weeks, peak at 12-14 weeks, declines by second trimester)
161
What sex differentiation occurs in utero?
wolffian ducts: male accessory sex organs derived from
In males, secretion of testosterone by Leydig cells causes growth and development of wolffian ducts into epididymis, vas deferens, seminal vesicles, and ejaculatory duct
müllerian ducts: female accessory sex organs derived from
in males, sertoli cells secrete müllerian inhibition factor (MIF) which causes the regression of the müllerian ducts beginning at day 60
- masculinization of external genitalia is due to secretion of testosterone by embryonic testes
* testosterone → (in target cells; 5-alpha-reductase) → dihydrotestosterone (DHT)
DHT needed for the development and maintenance of penis, male urethra, prostate, and scrotum
in absence of DHT, clitoris and labia majora are formed
testosterone is also converted to estradiol in neurons containing aromatase, a process necessary for normal male behavioral (sexual) function in mice → brain sexual dimorphication
162
What are the three general functions gonadotropins?
1) stimulation of spermatogenesis or oogenesis
2) stimulation of gonadal hormone secretion
3) maintenance of the structure of the gonads
163
Why is gonadotropin secretion pulsatile? What determines the pulsatile rhythm?
In order to prevent desensitization and downregulation of target glands.
The frequency and amplitude of pulses of secretion affect target gland response.
The pulsatile rhythm is provided based on excitatory stimuli from kisspeptins which are neuropeptide transmitters released from other hypothalamic neurons.
Kisspeptin is sensitive to leptin and other growth and metabolic factors, such that hormone secretion takes into account other body conditions like starvation
puberty is triggered by increased secretion of LH.
164
Describe the components of the testes.
seminiferous tubules - where spermatogenesis takes place; 90% of weight; FSH receptor proteins exclusively present in Sertoli cells; inhibin (inhibits FSH) also secreted by Sertoli cells
interstitial tissue - Leydig cells, blood and lymphatic capillaries for hormonal transport; LH receptor proteins exclusively present in Leydig cells
165
What effects do androgens have on the male body?
1) Sex Determination: growth and development of wolffian ducts into male anatomy; development of urogenital sinus into prostate; development of male external genitalia
2) Spermatogenesis
- Puberty - completion of meiotic division and early maturation of spermatids
- After puberty - Maintenance of spermatogenesis
3) Secondary Sex Characteristics: Growth and maintenance of accessory organs; growth of penis; growth of body and facial hair; body growth
4) Anabolic Effects: Protein synthesis and muscle growth; bone growth; growth of other organs (larynx); erythropoiesis
166
What is the process of spermatogenesis?
1) germ cells migrate from the yolk sac to the testes early in embryonic development - spermatogonia
- located in the outermost region of the seminiferous tubules, near the blood supply
- diploid cells that give rise to mature haploid gametes via
- only 1,000 to 2,000 initially migrate, but undergo mitosis, and only one proceeds through meiosis (primary spermatocyte)
2) Spermatogonia (2n)
3) Primary Spermatocyte (2n) → after mitosis
4) 2 Secondary Spermatocytes (n) → after first meiotic division
5) 4 Spermatids (n) → after second meiotic division
6) 4 Spermatozoa (n) → after spermiogenesis (differentiation via Sertoli Cells)
167
How do Sertoli cells aid spermatogenesis?
They are aligned on the basement membrane and form a continuous layer with tight junctions around the seminiferous tubules.
*blood-testis barrier, molecules from the blood must pass through the cytoplasm of Sertoli cells before entering germinal cells; also prevents immune system from being sensitized to antigens in the sperm, protecting against autoimmune destruction of sperm*
-respond to FSH; all effects of FSH are mediated by Sertoli cells
OVERALL: make the environment better for developing sperm
168
Describe the basic structure of the female internal sex organs.
Ovaries - two almond-sized organs suspended with ligaments from the pelvic girldle
Fallopian tubes - projections from these called fimbriae cover each ovary
Uterus - the womb; a pear-shaped muscular organ held in place with ligaments; lumen continuous with fallopian tubes
- Perimetrium: outer connective tissue layer
- Myometrium: middle smooth muscle layer
- Endometrium: inner epithelial layer
- ---Stratum basale, Stratum functionale (more superficial, cyclically gets thicker as a result of hormonal stimulation, shed at menstruation)
Uterus narrows to form the cervix which opens into the vagina, which has Labia minora (inner folds), labia majora (outer folds), and clitoris
169
Describe the steps in the ovarian cycle.
1) Primary oocytes that have not yet be stimulated to complete the first meiotic division are contained within primary follicles
2) In response to FSH stimulation (beginning in puberty), oocytes and follicles get larger, and follicular cells divide to produce layers of granulosa cells that surround the oocyte and fill the follicle
3) granulosa cells produce and secrete large amounts of estrogen
4) Further stimulation (by estrogen) yields the formation of fluid-filled vesicles, characterizing the follicle as a secondary follicle
5) Further stimulation sees the fusion of the vesicles into a single fluid-filled antruum, characterizing the follicle as a mature graafian follicle
6) The primary oocyte then completes its first meiotic division, forming only one secondary oocyte
only one cell gets the cytoplasm, in order to ensure a large enough ovum to be viable; other becomes a polar body which fragments and degrades
7) Secondary oocyte begins the second meiotic division, but arrests in metaphase II; division will only occur if fertilization occurs
170
What occurs during ovulation?
1) by 10-14 days after menstruation, only one follicle has succeeded in becoming a mature graafian follicle, and the others regress
2) the graafian follicle becomes so large that there is a bulge in the ovary, and ruptures, releasing the oocyte into the fallopian tube in a process called ovulation
3) If not fertilized, the oocyte degrades within a few days
4) The empty follicle, left behind in the ovary, undergoes structural and functional changes to become the corpus luteum, under the action of LH
5) corpus luteum secretes both estradiol and progesterone instead of just estradiol
6) Towards the end of a nonfertile cycle, the corpus luteum regresses and stops producing hormones, becoming the corpus albicans
171
What is the menstrual cycle, and what are the phases?
The periodic shedding of the endometrium, which becomes thickened prior to menstruation under the stimulation of ovarian hormones.
- duration of ~28 days
- conventionally, first day of menstruation is day 1 of the cycle
follicular phase - first day of menstruation through day of ovulation
luteal phase - after ovulation through first day of menstruation
172
How do hormone levels vary during the follicular phase?
1) during menstruation (day 1-5) ovarian steroid hormones at their lowest, only primordial and primary oocytes present
2) as follicles mature following menstruation, granulosa cells secrete estradiol, which reaches highest concentration at ~day 12
3) rapid rise in estradiol secretion from granulosa cells acts on hypothalamus to increase frequency of GnRH pulses, and increases pituitary’s ability to respond to GnRH with an increase in LH
4) FSH stimulates development of new FSH receptors, AND estradiol stimulates development of new FSH receptors
5) Toward the end of the follicular phase, FSH and estradiol also stimulate production of LH receptors on graafian follicles
6) In the very late follicular phase, there is an LH surge as a result of positive feedback mechanisms and production of LH receptors, triggering ovulation within 24 hrs
173
How do hormone levels vary during the luteal phase?
1) empty follicle is stimulated to become the corpus luteum, which secretes both estrogen and progesterone
2) peak progesterone levels approx. one week after ovulation
3) high levels of progesterone and estradiol exhibit negative feedback control on FSH and LH secretion; retards development of new follicles so that further ovulation does not occur in the same cycle
4) in late luteal phase, corpus luteum regresses and stops functioning; negative feedback from estradiol and progesterone keeps LH levels low, so its in a sense causing its own demise
5) decline of estrogen and progesterone cause menstruation and allows the start of a new cycle
174
Describe the cyclic changes in the endometrium.
Proliferative Phase
-When ovary is in follicular phase, increasing estradiol stimulates growth of stratum functionale of the endometrium, and the production of spiral arteries and progesterone receptor proteins
Secretory Phase
-When ovary is in luteal phase, increased progesterone secretion stimulates development of uterine glands, and the endometrium becomes thick, vascular, and spongy.
Menstrual Phase
-When ovarian hormone secretion falls in late luteal phase, constriction of the spiral arteries produces cell death of the stratum functionale, and it is shed with accompanying bleeding
175
What is the process of fertilization?
1) Sperm binds with the zona pellucida, triggering the entry of Ca++ to the acrosome
- In the acrosome reaction, the acrosomal membrane is fused with the plasma membrane, releasing acrosomal enzymes by exocytosis
- These enzymes allow sperm to digest a path through the zona pellucida to the oocyte
2) Fertilization stimulates the endoplasmic reticulum of the oocyte to release Ca++ via a second-messenger pathway
3) The spreading of the Ca++ from one side of the egg to the other in the Ca++ wave causes structural and metabolic changes that prevent other sperm from entering
4) The Ca++ wave also activated proteins that allow the cell cycle to continue past metaphase II
5) The second cell division produces one cell containing all cytoplasm, and one polar body, which fragments and disappears
6) Within 12 hours, cell membranes of ovum and sperm cell disappear, and haploid number of chromosomes from each join to form a zygote
- sperm cell contributes the centrosome
176
How does the fertilized egg begin dividing and implant?
1) 30-36 hrs after fertilization, the zygote divides by mitosis in a process called cleavage
- thereafter, rate of mitotic division speeds up
2) Early embryo enters the uterus three days after ovulation has occurred
3) By the fourth day after fertilization, a morula of 32-64 cells has been produced, but remains unattached to the uterine wall
4) By the fifth day, the morula undergoes changes to become a hollow structure called a blastocyst
including the 1) inner cell mass → fetus and the 2) chorion (trophoblast cells)→ placenta
5) By the sixth day, the blastocyst attaches to the uterine wall, with the side containing the inner cell mass against the endometrium
