QUIZ 4 Flashcards
1
Q
cellular respiration
A
- metabolism of glucose
- anaerobic
- aerobic
- production of ATP
2
Q
external respiration
A
- the movement of gases (oxygen and carbon dioxide) between the external environment and the cells of the organism
- coupled with cellular respiration
- byproduct is water
- CO2 waste product: exhale
3
Q
external respiration pt. 2
A
-major function of external respiration is gas exchange
-uptake of molecular O2 from environment
-discharge of CO2 into environment
-another major function is acid-base balance:
CO2 + H2O = H2CO3 = H+ + HCO3-
-animals require continuous supply of O2
-environmental reservoirs of oxygen
-atmosphere is major reservior (about 21% O2)
-Bodies of water also contained dissolved O2
-O2 is not very soluble in water
4
Q
cutaneous respiration: small or think animals
A
- small or thin animals can use their body surface for gas exchange
- ex. caenorhabditis elegans:
- no respiratory or circulatory systems
- O2 diffuses very slowly through water (about 3 million times slower than through air)
- all cell must be close the respiratory surface
5
Q
cutaneous respiration: large animals
A
- the body surface does not have enough area to support all of the cells
- specialized respiratory surfaces have evolved (gill, lung)
- in many animals a closed circulatory system with one or more hearts serves as a transport medium between cells and a specialized respiratory system
- however, not all animals with specialized respiratory surfaces transport O2 & CO2 via a closed circulatory system
6
Q
aquatic animals
A
- advantage of aqueous respiratory medium
- respiratory surfaces stay moist
- water not lost by evaporation
- disadvantage of aqueous respiratory medium
- O2 concentration relatively low
- therefore, exchange must be very efficient
7
Q
aquatic animal: gills
A
- gills originate as evaginations (out foldings) of the body surface
- in general, gills are organs that absorb dissolved O2 from an aqueous respiratory medium and excrete CO2
- can be located all over the body (sea stars)- papulae are small but everywhere- high SA
- can be restricted to a local body region (fish)
- gas exchange at gills is maximized by:
- large surface area
- counter current exchange- increase extraction from environment
- ventilation- increase water flow over gills
8
Q
counter current exchange
A
- partial pressure gradient (not concentration)
- gases diffuse down their partial pressure gradients
- concurrent exchange- blood flow and medium are flowing in the same direction, initially the pressure gradient is high and then gas transport averages out
- countercurrent exchange- medium and blood flow are opposite, concentration gradient is maintained along the length of the exchange surface -> greater extraction of O2 -> higher pressure of O2 in the blood
9
Q
aquatic animals: ventilation
A
- ventilation- any method of increasing contact between the respiratory medium and the respiratory surface
- usually requires expenditure of energy
- ex. ciliated surface, paddle-like appendages to push water over gills (lobsters, crayfish), swimming- increased water flow over gills (fish) “ram-vetilation”
10
Q
respiratory systems of echinoderms
A
- sea stars have external papulae that function as gills for gas exchange (tiny envaginations in the dermal skeleton)
- scattered over the body surface
- projects outward through a hole in the dermal skeleton
- cilia on the inner and outer surfaces beat in opposite directions, allowing counter current exchange of gases
- water flows in through the madreporite ->
- fluid in the coelom (body cavity) transports dissolved gases (water vascular system)
- the tube feet of sea stars are also important site of gas exchange
- movement is through hydrolic system
11
Q
teleost fish
A
- gills are anatomically localized in body surface
- body cells are distant from the respiratory surface
- large surface area for gas exchange
- water flow across lamellae and blood is flowing in opposite direction (venules to arterioles)
- ventilate by bulk flow of water over gills
- closed circulatory system- allows gases to and from distant tissues
- counter current exchange
12
Q
coupled respiratory and circulatory systems
A
- a strategy that has evolved in many animals is a 2 step exchange process involving a circulatory system
- step 1- exchange between respiratory medium (air or water) and circulatory system (open, closed) (through diffusion)
- step 2- exchange between circulatory system and interstitial fluid bathing cells (diffusion)
- circulatory system transports gases to and from tissues throughout the body
- allows for transport of gases to cells that are distant from the respiratory surface -> evolution of large animals
13
Q
terrestrial animals
A
- advantages of air medium:
- much higher concentration of O2
- O2 and CO2 diffuse faster in air
- air is easier to move- ventilation requires less energy
- disadvantage of air medium:
- *loss of water by evaporation
- respiratory surface may be folded into body
14
Q
terrestrail chelicerates
A
- spiders scorions (not insect)
- book lungs composed of series of very thin tissue ‘plates’ (lamellae) and look like pages of a book (increase SA)
- evolutionarily derived from book gills by ancestors
- lamellae project into an air filled chamber inside body
- air enters chamber by spiracle by diffusion
- gas exchange occurs across the thin walls of the lamellae
- oxygen enter hemolymph and is carried throughout the body in an open circulatory system
- circulatory system for distribution of dissolved gases
15
Q
tracheal system of insects
A
- tracheal system has evolved that doesnt rely on circulatory system for O2 and CO2 exchange
- air enters and exits through spiracles, which open to the exterior
- finest branches are tracheoles, which are thin walled structures (.2 um)
- tracheal tree
- air filled tracheae branch extensively and carry air deep throughout animals body
- end points of each branch are in direct contact with the bodys cells
- ends of tracheoles are filled with hemolymph
- hemolymph is used for gas exchange -> oxygen dissolved in the hemolymph before diffusing across the thin walls of the tracheoles and enter nearby cells (not distribution across body)
- flight muscle tissue have high metabolic rates -> tracheoles extend into invaginations of the muscle cell membrane (small diffusion distance)
- body movements compress the air sacs -> bulk flow
16
Q
tracheal system limit the body size
A
- largest insect now- atlas moth
- largest insect- dragonfly like (griffinflies)- wingspan of 2.5 feet, extinct
- diffusion of gases in the tracheal system limits body size
- higher atmospheric O2 levels during the paleozoic may have allowed the evolution of larger insects
17
Q
avian lungs
A
- vertebrate lungs originate as invaginations of the body surface
- in birds, system of air sacs allows unidirectional (one way) flow of air across the respiratory surface
- lung is stiff/rigid and undergoes very little change in volume during the respiratory cycle -> lungs are not inflated during inspiration the same way in mammals
- walls of the parabronchi have tiny blind-ended outpocketings called air capillaries that serve as the site of gas exchange
- air capillaries have extremely thin walls and do not expand significantly during inspiration
18
Q
mechanism of lung ventilation in birds
A
- first inspiration- (expansion of chest) air bypasses the lung and enters posterior air sacs
- first expiration- (compression of chest) air moves from posterior air sacs across the lungs respiratory surface
- second inspiration- (expansion of chest) air moves from lungs to anterior air sac
- second expiration- (compression of chest) air moves from anterior air sacs into the environment
19
Q
cutaneous respiration: larger animals
A
- some amphibians (frogs and salamanders) can exchange gases across their epidermis
- some salamander do not have lungs or gills and rely on cutaneous respiration
- gas exchange happens across the skin and epithelial layers of the mouth
- these animals use cutaneous respiration and are large -> bc they have a closed circulatory system and the body cells are distant from respiratory surface
20
Q
skin suffocation
A
- myth
- atmospheric oxygen is taken up by human skin but the contribution to total respiration is negligible
- atmospheric oxygen supplies the epidermis and dermis to a depth of .25-.4 mm
21
Q
mammalian respiration system
A
- lung for gas exchange
- localized respiratory surface
- most body cells are distant from lungs (closed circulatory system)
- nose/mouth -> trachea -> left/right primary bronchi (bronchus) -> bronchiole -> terminal bronchiole -> respiratory bronchiole -> aveolar duct -> aveolar sac -> aveolus (alveoli)
- 24 divisions
22
Q
diaphragm
A
- main muscle of inspiration
- ends are anchored to lower rib
- central tendon is lowered during contraction of diaphragm muscle -> increases volume of thoracic cavity
- mixed muscle- both fast and slow twitch fibers (good for rest and excerise)
23
Q
mammalian lungs
A
- mammalian lungs are anatomically localized and are not in direct contact with other parts of the body
- gap between lungs and other organs/tissues is bridged by the circulatory system
- dense network of capillaries associated with the lung epithelium
- allows efficient transfer of gases between the circulatory system and the external environment
- very short diffusion distance between air and blood
24
Q
respiratory bronchiole
A
- has a few aveoli associated with it
- little to none gas exchange here too bc of some aveoli presesnt on the bronchiole
25
aveoli
- site of gas exchange
- wall of aveoli are made of type 1 and 2 cells
- type 2 - secrete surfactant- reduces surface tension
- water is present in the aveolar chamber -> high surface tension -> surfacant reduces
- limited interstitial fluid (short diffusion distance)
- highly vascularized
- aveolar macrophage- ingest foreign material
26
fused basement membrane
- fused basement membranes- collagen & proteoglycans
- endothelial cell and type 1 aveolar cell are sharing the fused basement membrane
- not lipid bilayer
27
endothelial cells
-form capillaries
28
aveolar-capillary unit
-oxygen moves form alveolar air space -> across type 1 alveolar cell -> across fused basement membrane and endothelial cell -> to the plasma
29
conducting system
- trachea
- primary bronchi
- smaller bronchi
- bronchioles
30
exchange surface
- respiratory bronchioles
- alveoli
- SA is very high
31
at the aveolar-capillary unit, a molecule of O2 traverses a total of _ phospholipid bilayer membranes while diffusing from the alveolar air space (lumen of alveolus) to plasma
- 4
- endothelial cell membrane twice
- type 1 alveolar cell membrane twice
- if the O2 was to cross through the nucleus of the capillary it would be 6
32
pleural sac
- visceral pleural- up against lungs surface
- porietal- up against the body cavity
- in between is the pleural cavity filled with pleural fluid
- double membrane surround the lung
- elastic recoil
33
negative pressure in alveoloi
- facilitates air coming in and out
- outside pressure- 760
- when diaphragm is pulled down the chest volume increases
- elastic recoil creates inward pull
- elastic recoil of chest wall outwards
- opposing forces create negative pressure in pleural space relative to environment
34
external respiration
- air flow depends of differences in pressure
- air flow ~ pressure difference/ resistance to flow
- pressure difference= alveolar pressure - atmospheric pressure
- mammals exhibit negative pressure breathing
- pressure difference is negative during inspiration
35
positive pressure breathing
- air is mechanically forced into and out of the lungs
- endotracheal tube
- changes pressure gradient
36
negative pressure breathing
- diaphragm is the major muscle of inspiration
- during quiet breathing, inspiration is an active process (contraction of diaphragm) and expiration is a passive process (relaxation of diaphragm)
- during forceful breathing (strenuous exercise) additional muscles are recruited for inspiration (external intercostals) and expiration (internal intercostals)
37
sternocleido mastoids and scalenes
-also work to raise the thoracic cavity and increase volume
38
intercostals
- ribs muscles
- used during forceful breathing (exercise)
- inspiration and expiration
- mixed muscle- 60% type 1 fiber
39
pneumothorax
- if the sealed cavity is opened to the atmosphere, air flows in
- the bond holding the lung to the chest wall is broken and the lung collapses
- air in the thorax
- elastic recoil causes collapse
40
surfactant reduced the work of breathing
- surface active agents
- a thin layer of fluid lines each alveolus
- if this fluid layer is pure water a large amount of surface tension is generated due to the cohesive forces of water
- *surface tension apposes lung inflation
- complex mixture of proteins and phospholipids that disrupts cohesive forces of water and lowers the surface tension within alveoli
- more concentration in smaller alveoli, which equalizes the pressure in small and large alveoli
- surfactant is secreted by type 2 alveolar cells
- *reduces surface tension
- *equalized the pressure
41
small alveoli
- smaller alveoli more pressure -> more surfactant is needed
- P=2T/r
- equalized pressure
- reduced surface tension
42
surfactant example
-aveoli 1- small
-aveoli 2- large
NO SURFACTANT
-if alveoli 1 and alveoli 2 have equal surface tension
-alveolus 1 has higher pressure than 2
-alveolus 1 is likely to collapse as air moves to alveolus 2 (high pressure to low)
SURFACTANT
-alveolus 1 has less surface tension due to more surfactant per unit surface area
-alveoli 1 and 2 have equal pressure
43
premature human babies
- lung may be under developed
- inadequate surfactant concentrations
- newborn respiratory distress syndrome- was once leading cause of infant death
- corticosteroids given to the mother can accelerate the development of the fetal lung
- artificial surfactants are available
- positive pressure breathing (mechanical ventilation)
44
spirometry
- measuring ventilation extension of lung function
- bell moves up and down in water
- as you breathe in bell goes down vice versa
- pulley system
- positive inflection- inspiration
- negative deflection- expiration
45
tidal volume
- 500ml
- what you normally breathe in and out
- the volume of air moved in and out of the lungs during normal quiet breathing
46
expiratory reserve volume
- additional volume of air that can be expired from lungs by forceful effort following normal expiration
- 1100 ml
47
residual volume
- even when you forcefully breathe out there is still air in your lungs
- vol of air remaining in lungs at the end of a forced exhale
- this is bc there are cartilaginous rings that cant be compressed
- 1200ml
48
inspiratory reserve volume
- max volumeof additional air that can be drawn into the lungs by a forceful effort following a normal inspirations
- inhaling forcefully
- 3000ml
49
vital capacity
- the maximum effort
- maximal inhale and maximal exhale
- capacity- sum of one or more volumes
- tidal vol + inspiratory reserve vol + expiratory reserve vol
- 4600 ml
50
total lung capacity
- maximum inhale (inspiratory reserve vol)
- maximum exhale (expiratory reserve vol)
- plus the residual volume
- plus tidal volume
51
emphazema
- destruction of alveoli
- lung is less compliant
- total lung capacity increases
- hard time expiring air
- residual vol increases
52
lung fibrosis
- fibrotic tissue destruction
- difficult to inflate
- total lung capacity decreases
53
dead space
- technically not a lung volume or capacity
- volume of air remaining in airways at the end of each exhalation
- 150 ml
- a consequence of bi-directional flow through airways
- mixes with fresh air during inhalation
54
alveolar ventilation
- volume of fresh air reaching alveoli per min: (volume of fresh air per breath reaching alveoli) x (number of breaths per min)
- need to consider effect of dead space: (vol of fresh air per breath reaching alveoli) = (breath vol - dead space)
- ex. consider an adult breathing with normal tidal vol (500 ml) at 12 breath per min. ->
- total pumonary ventilation- 500ml/breath x 12 breath/min = 6L/min
- alveolar ventilation- 500-150ml/breath x 12 breaths/min = 4.2 L/min
55
increasing breath volume
more effective at increasing alveolar ventilation
56
ventilation
- bulk flow
- no atp
- no carrier proteins
- main stimulus for regulation ventilation is CO2
57
overview of O2 and Co2 exchange and transport
-high partial pressure of O2 in alveoli -> moves from alveoli into circulatory system -> pumped systemically-> low partial pressure of O2 in tissues -> O2 moves into tissues -> acts as final electron acceptor for aerobic respiration -> CO2 product -> low partial pressure in circulatory system -> moves into circulatory system -> majority of CO2 is transported as HCO3- -> moves into pulmonary circulation which has high partial pressure of CO2 -> CO2 moves into alveoli -> expired
58
partial pressure of a gas
- in a mixture of gases (atmosphere), the amount of pressure due to a specific gas is the partial pressure of that gas
- difference in partial pressure is the driving force for diffusion of gas
- gases diffuse from a region of high partial pressure to low
- ex. @ sea level air pressure is 760 and air is 21% O2 -> .21 x 760 = 160 partial pressure O2
59
gases in solution
-at equilibrium partial pressure is equal but concentration is not
60
ficks law of diffusion
- diffusion of gases (O2 and CO2) between lung and blood (or between blood and cells) obey ficks law of diffusion
- dQ/dt =D * (P2-P1)
- D- diffusion coefficient- directly proportional to surface area and inversely proportional to diffusion distance
- (P2-P1)- pressure gradient of gas is the driving force of diffusion
- usually, factors determining D are constant -> the most important factor is the pressure gradient (driving force)
61
O2 and CO2 partial pressures
- Atm- PO2 160, PCO2 .25
- alveoli- PO2 100, PCO2 40
- arterial blood- PO2 100, PCO2 40
- cells- PO2 < 40, PCO2 > 46 (diff tissues have diff levels of metabolic rate at diff times)
- venous blood- PO2 < 40, PCO2 > 46
62
partial pressure from alveoli to arterial blood
same because of bulk flow
| -there is no diffusion across the walls of the heart chambers
63
oxygen transport
- oxygen is not very soluble in aqueous solutions
- little dissolved O2 even when partial pressure of O2 is high
- oxygen is carried by respiratory pigments: hemocyanins and hemoglobin
64
hemocyanins
- copper binds oxygen (arthropods, molluscs)
- arthropods: 3 protein subunits
- mulluscs: 2 protein subunits
- blue domains each have 2 copper atoms; each copper atom is coordinated by three histidine (HIS) residues
- one oxygen per heomcyanin
65
hemoglobin
- iron-containing heme group (protoporphyrin IX) binds oxygen
- 98% of the O2 content of blood carried by hemoglobin in humans
- four protein subunits (4 polypeptide chains: 2 alpha and 2 beta in adults)
- each subunit contains one heme group
- one iron atom at the center of each heme group binds one O2 molecules -> 4 O2 for one hemoglobin
- coordinate covalent bond between the oxygen and iron (electron pair coming from O2) -> very reversible
- binding at the lung is favored due to high partial pressure of O2 at lung
66
heme group
- prosthetic group
- ring structure
- stable
- porphyrin ring
- iron bonds to oxygen
- 4 heme groups per hemoglobin -> 4 oxygen
67
red blood cell
- lack of organelles
- biconcave structure
- cytoskeleton in the plasma membrane -> anchored protein interactions here generate the force that give it shape
- advantages of the biconcave structure:
- most hemoglobin is positioned close to the cell membrane, reducing the diffusion distance of O2
- allows the RBC to bend and twist while negotiating tight passages in the capillaries
68
bird RBC
- football shape
- birds are optimized to extract oxygen from air
- explains football shape
69
sick cell disease
- become hydrophobic
- tends to polymerize and form chains
- aggregates that precipitate and deform shape into crescent
- can obstruct blood flow in small vessels
- clogs
- mutation is not in heme group
70
oxygen transport in blood
- oxygen enters the circulatory system from the alveoli by diffusing down its concentration gradient
- 2% is dissolved in plasma and 98% binds to hemoglobin in RBC
- Hb is transported through tissues
- partial pressure gradient favors dissociation of O2 into tissues (coordinated covalent bond broken)
- O2 acts as the final electron acceptor in aerobic respiration
71
hydrogen ions affect the conformation of hemoglobin
- decreased binding affinity of O2 to hemoglobin
- pH decreases in very active tissue due to high PCO2
- increased release of O2 from hemoglobin in capillary beds of active tissues
- other factors can also cause a rightward shift in the HbO2 curve:
- increase in temp
- high PCO2
- 2,3 bisphosphoglycerate
72
Bohrs shift
- hemoglobin O2 dissociation curve is shifted
- as you run around you generate CO2 and H+ concentration and 2,3 bisphosphoglycerate
- H+ ions bind to hemoglobin causing the right ward shift
- @ rest PO2 P50 is 27 mmHg
- hemoglobin has lower affinity for O2 (gives of O2 easy) when you are active
73
myoglobin
- respiratory pigment in muscle
- monomer
- concentration highest in muscles that rely on aerobic metabolism (red muscle, dark meat)
- has a single polypeptide chain and one heme group
- one porphyrin ring
- can bind one O2 (hand-off)
- much higher affinity for O2 than Hb
- more than 80% saturated at a PO2 of 20 mm Hg (a point where hemoglobin has given up most of its O2)
- O2 reserve in muscles
- leftward shift for P50 value -> higher affinity
74
maternal and fetal hemoglobin have different O2 binding properties
-fetal hemoglobin has a higher affinity for O2 than maternal
75
smaller P50
high affinity for O2
76
cooperativity in oxygen binding hemoglobin
- hemoglobin curve is sigmoidal
- binding of O2 in Hb causes a conformational change
- conformational change causes causes subsequent O2 molecules bind with higher affinity
- cooperativity in O2 binding -> sigmoidal shape of the Hb-O2 curve
- vice versa with unbinding!
77
CO2 transport in the blood
- CO2 is soluble in water (and blood plasma)
- 7% is dissolved
- 23% bound to amino groups (Hb)
- 70% bicarbonate buffer system
78
bicarbonate buffer system
CO2 + H2O ->
79
CO2 transport in blood
- high partial pressure of CO2 in tissue
- 7% dissolves into plasma
- most is transported at bicarbonate in RBC
- bicarbonate then moves out of the RBC in exchange for Cl- moving in
- bicarbonate is in the circulatory system and goes to the lungs
- reverse bicarbonate reaction occurs producing CO2
- low partial pressure in alveoli causes CO2 to diffuse in
80
Bohr shift refers specifically to phenomenon where the binding affinity of Hb for O2 decreases in metabolically active tissue with elevated pH
- false
| - everything is true except it is low pH not elevated
81
respiratory drive
- physiological drive to breath
- some voluntary some involuntary
- some factors that affect the rate and depth of breathing:
- PCO2, PO2, pH
- emotions
- sleep
- lung inflation
- speech
- conscious volition
82
control of ventilation
-high partial pressure of CO2 in plasma
-CO2 diffuses across blood brain barrier (H+ cannot)
-carbonic anhydrase combines CO2 with water and forms carbonic acid which dissociates into bicarbonate and H+
-central chemoreceptor senses the H+ ion binding -> increases sodium influx -> depolarization -> action potential -> activation of somatic motor neurons -> increase ventilation, increase contraction of diaphragm and external intercostal muscles
increased ventilation increases PO2 and decreases plasma PCO2
-negative feedback
83
medulla & pons
- central pattern generator for breathing
- neurons in the medulla that fire spontaneously
- generate the rhythm of breathing
- similar to SA node mechanism except it innervates skeletal muscle (diaphragm)
- integrate information
- changes the firing rate of somatic efferent neurons that innervate inspiration and expiration muscles
84
cerebral cortex
- deciding consciously how to breathe
| - deciding to hold your breathe
85
peripheral chemoreceptors and central chemoreceptors
- responding to CO2
- specific stimulus is H+ ions
- carotid and aortic chemoreceptors
- O2 and pH can regulate but only under extreme low PO2 plasma levels
86
hyperventilation
- increases the partial pressure of O2 in alveoli
- no increase in blood content of O2
- this is because even at 100 mm Hg hemoglobin is already saturated
- blows off more CO2 (less available)-> bicarbonate equation is in reverse:
- increases pH of CSF
- decrease H+
- decreases respiratory drive
87
hypoventilation
- increase plasma PCO2
- decreases pH of CSF
- increases respiratory drive
88
hyperventilation increase the pH of CSF and decreases the pH of plasma
- false
- it does increase the pH of CSF
- plasma and CSF are parallel
- they both increase
89
asthma
- very common
- exaggerated immune response to trigger
- inflammed airways
- excess mucus
- contraction of smooth muscle in the airways
- reduces airway caliber
- difficulty exhaling
- relaxation of the diaphragm is not sufficient
- there are many triggers
- maintenance medication- regular basis, drug is delivered directly to airways (includes fluticasone, a steriod, similar to cortisol)
- rescue medication- quickly relaxes airway muscles
90
Beta 2 adrenergic agonists
- inhaled, short acting: albuterol, bitolterol, terbutaline
- inhaled, long acting: salmeterol, formoterol
- based upon endogenous hormone norepinephrine (bind to the same receptor)
- agonist binds to beta 2 adrenergic receptor -> acts on adenylate cyclase -> produce cAMP -> activates PKA -> airways smooth muscle relaxation -> airways caliber increases
91
there are 24 airway branches
- false
- there are hundred of millions
- there are 24 divisions
92
external intercostal muscles participate in expiration
false
93
inspiratory reserve volume is greater than expiratory reserve volume
true
94
Functions of the mammalian kidney
- regulation of ECF volume and blood pressure
- filtration -> 99% of it is reabsorbed
- regulation of osmolarity (inorganic ion balance: Na, K)
- Elimination of metabolic waste products (urea, uric acid, creatinine)
- removal of foreign chemicals (pesticides, drugs, foods, additives)
- gluconeogenesis (during periods of prolonged fasting)
- secretion of hormones and an enzyme:
- erythropoietin (stimulates RBC production)
- 1,25-dihydroxyvitamin D3 (important for Ca homeostasis)
- *renin (an enzyme that generates the precursor of angiotensin 2, which influences Na and K homeostasis and blood pressure
95
reabsorption
- there is no primary active transport for water
- > they reabsorb solutes (Na)
- diffusion
96
ureter
where the urine exits the kidney to the bladder
97
urinary bladder
- smooth muscle
| - expands
98
anatomy of the kidney
-cross section- kidney is divided into an outer cortex and an inner cortex
-urine leaving the nephrons flows into the renal pelvis prior to passing through the ureter into the bladder
-outer capsule surrounds
-under capsule is cortex
-under cortex is medulla
-1 million nephrons per kidney
-
99
nephrons
- functional unit of the kidney
- filters blood
- two arterioles and two sets of capillaries = portal system
100
medulla
- contain arcuate arteries and veins
- arcuate arteries arch into the afferent arterioles
- afferent arterioles lead into the glomerulus (millions)
- leaves the glomerulus by efferent arterioles
- drained by arcuate vein
101
glomerulus
- each one is a ball of capillaries
- site of blood filtration
- enters the glomerulus through afferent arteriole
102
cortical nephron
- shorter loop of henle
- many peritubular capillaries associated (a lot of exchange between blood and nephron) -> allows exchange
- shorter -> less water reabsorption -> less concentrated urine
103
juxtamedullary nephron
- long loop of henle
- many peritubular capillaries associated (a lot of exchange between blood and nephron) -> allows exchange
- vasa recta- longer peritubular -> more change for exchange
- bc its longer more water can be absorbed -> more concentrated urine
104
vasa recta
- in the juxtamedullary nephron
- longer peritubular capillary
- allows for more chance of exchange
- much more water reabsorption here
- water reabsorption happens descending in loop of henle
105
collecting duct
- regulation of water reabsorption
| - many nephrons will merge and move into one collecting duct
106
bowmans capsule
- collects filtrate
| - first part of the nephron
107
anatomy of nephron
- starts with bowmans capsule (glomerulus is here)
- goes to the proximal tubule
- down to the descending limb
- bottom is called loop of henle
- goes up the ascending limb
- reaches the distal tubule
- lastly, goes to collecting duct
- ureter -> bladder
108
function of the nephron
- filtration
- reabsorption
- secretion
- excretion (urine)
109
filtration
- site of blood filtration- glomerulus
- podocytes surround capillaries- foot processes
- hydrostatic pressure in capillaries forms ultrafiltrate
- ultrafiltrate move through endothelium into bowmans capsule
- mesangial cell- phagocytes that prevent clogging of proteins
110
glomerular capillary: 3 layer filtration barrier
1. endothelium- has fenestration (pores)- large particles cant move through
2. basement membrane- extracellular matrix -> collagen/proteoglycans
3. podocytes- foot processes -> slit diaphragm- complex of proteins
111
ultrafiltrate
size selective
| -180 L form a day
112
driving force
- hydrostatic pressure (blood pressure within glomerular capillaries)
- colloid osmotic pressure due to proteins in plasma but not in bowmans capsule
- fluid pressure due to fluid in bowmans capsule
- hydrostatic pressure - colloid osmotic pressure - fluid pressure = net filtration pressure
113
afferent arteriole
- primary site of regulation -> glomerular filtration rate (GFR)
- surrounded by smooth muscle that can vasoconstrict/dilate
- constriction -> increase in resistance, decrease flow, decrease hydrostatic pressure, decrease GFR
- dilation- decrease resistance, increase flow, increase pressure, increase GFR
114
autoregulatory (intrinsic) control
- myogenic response
| - tubuloglomerular feedback
115
extrinsic control
-neural and hormonal regulation of afferent arteriolar diameter
116
myogenic response: intrinsic
- blood pressure can vary dramatically
- GFR remains constant between 80-180 BP
- normal MAP = 93
- increased pressure -> smooth muscle vessel walls stretch
- mechanosensitive ion channels (Na) in the arteriole wall activate
- depolarization -> Ca release -> contraction of vascular smooth muscle cells (vasoconstriction) -> decrease blood flow -> decrease in pressure
117
MAP
-CO x system vascular resistance=MAP
118
tubuloglomerular feedback: intrinsic
- nephron wraps around on itself
- ascending limb of loop of henle senses fluid flow (macula densa cells are here)
- an increase in filtration -> increase in ultrafiltrate -> increase if GFR -> macula densa cells sense increased flow -> paracrine factors are released (adenosine) from macula densa -> afferent arteriole vasocostriction -> decrease in hydrostatic pressure -> decrease in GFR
119
neural and hormonal regulation of afferent arteriolar diameter: extrinsic
- most occurs via afferent arteriole
- smooth muscle cells of the afferent arterioles have alpha 1 receptors for norepinephrine to vasoconstrict
1. neural
- sympathetic neurons innervate the afferent arteriole and release norepinephrine
- afferent vascular smooth muscle cells have alpha-adrenergic receptors that mediate vasoconstriction in response to norepinephrine
- fight or flight response -> constrict -> blood flows to other organs in need (hemorrhage)
- significant blood loss
2. hormonal
- many hormones like angiotensin 2 is a vasoconstrictor that reduces GFR
120
vasoconstriction of the efferent artiole (afferent remains unchanged) would increase hydrostatic pressure in the glomerular capillaries and increase glomerular filtration rate (GFR)
- true
- exit is reduced
- pressure is still increased in the glomerular capillaries
- same amount of blood coming in and less coming out -> increase pressure
- filtration increases therefore
121
filtration fraction
- 100% of blood volume in afferent arteriole (not 100% CO)
- 80% passes through glomerulus and bowmans capsule (20% is filtered)
- of that 20% more than 19% is reabsorbed
- less than 1% is excreted as urine
122
reabsorption of water
- solutes are reabsorbed
- mostly Na (also anions, K, Ca, urea) bc it is the main determinant in ECF volume
- solutes move from the tubule lumen past the tubular epithelium and into the extracellular fluid
- water follows solute through aquaporins
- solutes use a variety of primary and secondary active transport
123
passive transport
- urea
- ultrafiltrate forms
- solutes are being transported and water is following
- this leads to concentrated urea bc water is being reabsorbed
- this results in a concentration gradient for urea and its able to diffuse passively into the fenestrated peritubular capillary
124
sodium reabsorption
- active transport
- Na/k atpase pump
- moving against gradients
- on the basolateral surface there is active transport of Na and K pump
- on apical surface (tubule lumen side) there are open channels that move Na down concentration gradient (created by atpase pump) with glucose against its concentration gradient -> secondary transport
125
glucose: secondary active transport
- Na gradient created on apical surface allows for Na to diffuse down its concentration gradient
- brings glucose with it against its concentration gradient
- uses SGLT protein (antiporter)
- glucose then diffuses across the basolateral surface using GLUT protein (facilitated diffusion)
- secondary active transport
126
renal secretion
- secreted into the lumen
- enhances excretion capability
- active process
- secretion of K and H+ important for hemostatic regulation
- several organic compounds (penicilin) are secreted
127
renal excretion
- a measure of overall kidney function
- can be measured in a non-invasive way (clearance)
- renal clearance can be used to assess kidney function
- summation of what gets filtered reabsorbed and secreted
128
3 pathways
- penicillin- secretion > filtration
- Na, H20, urea- reabsorption > secretion
- glucose, amino acids- all is filtered and reabsorption (no secretion)
129
penicillin
- most is secreted
- treats bacterial resistance
- probenicid- blocks secretion through competitive mechanisms
130
glucose filtration
- no secretion, all reabsorbed
- freely filtered
- small organic molecule
- filtration of glucose is proportional to plasma concentration
- filtration does not saturate
- as you increase plasma glucose level filtration rate of glucose increases infinitely
131
glucose reabsorption
- reabsorption of glucose is proportional to plasma concentration until transport maximum (Tm) is reached
- Tm= 375 mg/min
- transporter is saturable
132
glucose excretion
- excretion = filtration - resorption
- normally excretion is zero
- at renal threshold is starts to increase
- renal threshold = 300 mg/100 mL plasma
- diabetic have glucose in urine
133
type 1 diabetes mellitus
- autoimmune disease: destruction of beta cells in pancreas
- insulin hyposecretion (formerly called insulin dependent diabetes mellitus)
- hyperglycemia: significantly elevated plasma glucose
- glucosuria: glucose in urine
- damage to blood vessels, eyes, kidneys, CNS
- polyuria: excessive urine production- osmotic diuresis
- polydipsia- excessive thirst
- polyphagia- excessive hunger
134
type 2 diabetes mellitus
- formerly called non-insulin dependent diabetes
- thought to be principally a disease caused by lifestyle factors (being overweight and sedentary)
- 97% of all diabetics are type 2
- common hallmark is insulin resistance, particulary in muscle and adipose tissue
- glucose tolerance test- cannot differentiate between problems with insulin secretion, synthesis or end-organ responsivity
- hyperglycermia
- most effective treatments combine weight reduction and exercise
- atherosclerosis, renal failure, blindness, neurological damage
- 70% die from cardiovascular disease
135
following consumption of spaghetti, blood glucose levels in a diabetic may peak at 200 mg/dl or higher, because renal filtration of glucose saturates
- false
- reabsorption is saturating
- filtration cant saturate
136
glycated hemoglobin
- HbA1c assesses glucose load
- long term indication of blood glucose levels
- HbA1c becomes modified covalently with glucose
- degree of modification depends upon glucose load
- hemoglobins half life is long (2 months) so we can see changes over time
- blood glucose 90 -> HbA1c 5%
- blood glucose 360 -> HbA1c 14%
137
transporters
- move glucose into circulation
| - SGLT1 and SGLT2
138
SGLT1
- mostly in small intestine, some in kidney and heart
- late proximal straight tubule
- high affinity for glucose
- low capacity for glucose transport
- 10% of renal glucose reabsorption
139
SGLT2
- almost exclusively in kidney
- early proximal convoluted tubule
- low affinity for glucose
- high capacity for glucose transport
- 90% of renal glucose reabsorption
- drug target bc low affinity and high capacity and not expressed elsewhere, accounts for a lot
- canagliflozin- drug that blocks SGLT2 reabsorption
- problem is that glucose is going in the urinary tract -> UTIs
140
amount of soloute excreted
= amount filtered - amount reabsorbed + amount secreted
141
renal clearance
- method of quantifying renal function
- non-invasive diagnostic procedure to measure GFR
- defined as the volume of blood plasma that was cleared of a substance has been completely removed (cleared) per unit of time
- volume/time (mL/min)
- clearance is a rate
- ex. glucose is normally 0 anything above is abnormal
- a substance that is freely filtered, but NOT reabsorbed and NOT secreted would be ideal to determine clearance -> inulin
- if filtration and excretion are the same, there is no net reabsorption or secretion, and the clearance of a substance equals GFR
142
inulin
- plant carbohydrate
- exogenous
- ideal properties -> freely filtered and not reabsorbed or secreted
- humans do not have transporters for this -> injection
143
example of inulin clearance
- 100ml of plasma and 4 molecules of inulin
- inulin is freely filtered and hydrophilic
- inulin is trapped in lumen (no transporters for inulin)
- 0% reabsorption and 0% secretion
- plasma is being reabsorbed and secreted
- 100% inulin excreted -> inulin clearance 100mL/min
- GFR= 100mL/min
- inulin clearance = GFR (no secretion or reabsorption)
144
example of glucose clearance
- soluble, freely filtered
- 100mL of plasma
- glucose is 100% reabsorbed bc of glucose transporters (simporter, facilitative transporter)
- clearance rate is 0
- 0% glucose excreted
- Cinulin > Curea
145
example of urea clearance
- net resorption
- filtration > excretion
- 100mL plasma, 4/100mL plasma concentration
- freely filtered
- 50% of urea is reabsorbed, 50% urea excreted
- 50mL/min urea clearance
- Cinulin > C urea
- 2 urea/min excreted
146
net secretion
-if clearance of a substance is greater than GFR -> net secretion
147
example of penicillin clearance
- excretion > filtration -> net secretion
- 100mL of plasma
- 4/100mL plasma concentration
- freely filtered
- penicillin is actively secreted from the peritubular capillaries into the proximal tubule of the nephron -> more penicillin excreted than was filtered -> 6pinicillin/min
- plasma reabsorbed, 0% penicillin reabsorbed
- penicillin clearance= 150 mL/min
- Cinulin
148
real world example of clearance
- inject precise drug dose into rat tail vein
- collect urine 10mL of urine over 10 hours
- concentration of drug in urine = 1 mg/ml
- rate of appearance of drug in urine = (10mL x 1 mg/ml)/10 hour = 1 mg/hour -> excretion rate
- clearance = (rate of appearance of drug in urine)/(plasma concentration of drug)
- measured plasma concentration = 1mg/mL
- clearance = (excretion rate)/(plasma concentration of drug) = 1 mg/ml
149
clearance=
excretion rate/plasma concentration of drug
-excretion rate= rate of appearance of drug in urine = (volume of urine collected x concentration of drug in urine)/collection time
150
important generalization about clearance
1. Cinulin = GFR (ml/min)
2. If Csubstance > Cinulin, then substance is filtered and secreted (on a net basis)
3. If Csubstance = Cinulin. then substance X is filtered, not secreted and not reabsorbed (on a net basis)
4. If Csubstance < Cinulin, then substance X is filtered, secreted and reabsorbed (on a net basis)
5. creatinine is the closest naturally occurring substance with clearance values approx those of inulin
6. Ccreatine (about)= GFR = Cinulin
151
units for clearance are mL/min, and the mL refers to volume of urine collected
- false
| - mL= vol of blood plasma
152
physiological regulation of H2O, Na, and K
1. Na reabsorption is an active process
2. H2O reabsorption is by osmosis (diffusion) and will follow Na reabsorption (when possible)
3. Na reabsorption and H2O reabsorption are independently regulated
- regulatory systems:
- arginine vasopressin (AVP) / Antidiuretic hormone (ADH)
- renin-angiotensin aldosterone system (RAAS)
- natriuretic peptides
153
decrease in blood volume and blood pressure
- volume receptors in the atria and carotid and aortic baroreceptors detect (stress receptors) -> trigger hemostatic reflexes
- decrease firing rate decrease stretch -> less activation of inhibitory interneurons -> less negative input to sympathetic neurons -> increase rate of release of norepinephrine ->
- norepinephrine acts on the heart (SA node) -> increase heart rate/contraction through beta 1 receptors -> increase CO -> act on alpha receptors -> vasoconstriction -> increase resistance -> increase MAP
- behaviorally -> drink water -> increase ECF & ICF volume -> increase BP
- kidney hormones work to conserve water
154
decrease in blood volume and blood pressure
volume receptors in atria, endocrine in atria, and carotid and aortic baroreceptors
- muscles are stretched
- release peptide hormones atriorectic factor
- inhibit release of renin
155
kidneys conserve volume
- kidneys return water to the circulatory system
- consume more water -> excrete more water -> less being returned
- proximal tubule isosmotic to plasma -> as it goes down loop of henle water is reabsorbed through aquaporins (interstitial vol is hyperosmotic) -> as it ascends ions reabsorbed (no aquaporins are here)
- in distal tubule and collecting duct water reabsorption is primary regulated by vassopresin
- 50-1200 mOsM urine is excreted
156
vasopressin (AVP)
- controls the trafficking of vesicles that contain aquaporin channels
- vasopressin is controlling the permeability by controlling the trafficking of aquaporins at the apical surface @ collecting ducts
- made in the hypothalamus -> nerve cell body synthesize AVP
- hormone is packaged in vesicles and transported down axon and stored and await for release in posterior pituitary (NOT bound by carrier protein)
- released into the blood
- increase is plasma osmolarity signals the release of AVP
157
H2O movement
- can only occur if epithelial cell membranes are permeable to H2O (if aquaporin channels are present)
- H2O permeability is high in the proximal and distal tubules and is reabsorbed by osmosis in constant proportions following reabsorption of solutes
- H2O permeability is high in the descending loop of henle and essentially zero in the ascending
- H2O permeability in the collecting duct can be high or low and is regulated by vasopressin
158
Na and H2O reabsorption
- sodium is actively reabsorbed and water follows Na by osmosis
- Na actively transported on basolateral membrane
- gradient formed allows Na to diffuse passively in the apical surface
- if aquaporins are present in apical surface it can move past due to Na gradient
- vasopressin is controlling the permeability by controlling the trafficking of aquaporins in collecting ducts (apical surface)
- The movement of Na+ from the interstitial space surrounding the proximal tubule cells into the peritubular capillary blood does not require active transport
159
bulk flow
-water moves into the peritubular capillaries by bulk flow
160
triggers for vasopressin (AVP)
1. decreased blood pressure -> sensed by carotid and aortic baroreceptors -> sensory neuron to hypothalamus -> hypothalamic neurons synthesize AVP
2. decreased atrial stretch due to low blood volume -> sensed by atrial stretch receptor -> sensory neuron to hypothalamus -> hypothalamic neurons synthesize AVP
3. osmolarity greater than 280 mOsM -> sensed by osmoreceptors in the hypothalamus -> interneurons lead to hypothalamus neurons that synthesize AVP
161
regulation of vasopressin
- hypothalamic neurons synthesize AVP
- vasopressin (AVP) released from posterior pituitary
- affects collecting duct epithelium
- *insertion of water pores in apical membrane
- increased water reabsorption to conserve water
162
insertion of aquaporin water channels in apical membrane
- vasopressin binds to cell surface receptor (g-protein coupled) on basolateral membrane
- cAMP released and activates PKA -> phosphorylates substrates (aquaporin-2 water channel subunits) -> exocytosis of vesicles containing aquaporins at apical surface
- aquaporin-2 responds to vasopressin
163
max vasopressin
- collecting duct is freely permeable to water
- water leaves by osmosis and is carried away by vasa recta capillaries
- reabsorption
- urine will be concentrated
164
diabetes insipidus
- loss of ability to produce AVP (central diabetes insipidus)
- loss of vasopressin receptors (nephrogenic diabetes insipidus)
- results in a constant H2O diuresis -> large volume of dilute urine due to lack of water resorption
- not the same as an osmotic diuresis
- H2O diuresis is not due to excessive solute loss
- osmotic diuresis: H2O loss is due to excessive solute loss (water follows solute)
165
diabetes mellitus
- hyperglycemia (high glucose levels)
- glucosuria
- polyuria (osmotic diuresis)
- polydipsia -> thirst
- polyphagia -> hungry
166
Renin-angiotensin-aldosterone system (RAAS)
- loss of blood volume -> decrease blood pressure -> decrease GFR
- decrease in NaCl transport across macula densa cells of distal tubule
1. paracrine factors released -> signal granular cells (smooth muscle cells in wall of afferent arteriole) -> produce renin
2. granular cells have beta 1 receptors that are also being signaled by increase in sympathetic activity due to decrease in BP -> produce renin
3. bc granular cells are smooth muscles in the afferent arterioles they are directly reacting to decrease in BP -> produce renin
167
renin is an enzyme
- respond to reduction of flow and BP
- decrease in blood volume -> decrease in GFR -> less flow past macula densa cell -> paracrine factors
- granular cells secrete renin
- renin- involved in salt and water balance
- liver constantly produces angiotensinogen in plasma which is a substrate for renin -> cleaves -> produces angiotensin 1 in the plasma -> ACE cleaves angiotensin 1 into angiotensin 2
168
angiotensin converting enzyme
- ACE
- cleave angiotensin 1 into angiotensin 2 in response to decrease in BP
- inhibitors of ACE decrease BP
169
angiotensin 2
- increases blood pressure
- hormone in plasma that affects other hormones
1. acts on hypothalamus which increases thirst and vasopressin secretion -> increase volume and maintain osmolarity -> increase BP
2. acts on adrenal cortex which increases aldosterone secretion -> increase Na reabsorption -> increase in volume and maintain osmolarity -> increase BP
3. acts on proximal tubule -> increases Na reabsorption -> increases volume and maintain osmolarity -> increase BP
4. acts on arterioles -> vasoconstriction (alpha 1 mostly skin and GI tract) -> increase BP
5. act on cardiovascular control center in medulla oblongata -> increase sympathetic output -> increases cardiovascular response (beta 1 HR and contraction) -> increase BP
170
aldosterone
- steroid hormone
- targets the collecting ducts
- increases Na reabsorption
- increases K secretion
- made in adrenal gland (adrenal cortex)
171
importance of K in plasma
- most abundant intracellular ion (only 2% in ECF)
- extremely important for maintenance of resting membrane potential in all excitable tissue
- hyperkalemia- high K plasma, depolarizes cells, can lead to life-threatening cardiac arrhythmias
- hypokalemia- low K plasma, hyperpolarizes cells, can lead to failure of respiratory and cardiac cells to contract
172
renal regulation of K
- collecting ducts
| - regulated by aldosterone
173
aldosterone triggers
1. high K concentration (hyperkalemia) or very high osmolarity -> signals adrenal cortex -> produces aldosterone -> act on level of collecting duct -> increase Na reabsorption and K secretion into lumen
2. low BP -> RAAS pathway -> signal adrenal cortex -> produces aldosterone -> act on level of collecting duct -> increase Na reabsorption and K secretion into lumen
174
mechanism of aldosterone
- steroid -> hydrophobic -> diffuses across lipid bilayers
- binds to cytosolic receptor (inducible transcription factor) in the P cells of distal nephron -> causes translocation to the nucleus -> controls transcription
175
overproduction of aldosterone
- hypertension
- due to excess Na reabsorption
- hypokalemic -> excessive loss of K
176
aldosterone is synthesized by cells of the adrenal cortex and stored in vesicles
- aldosterone is a steroid
- steroids are hydrophobic and are not packaged
- it would diffuse out
- steroids are also made on demand (not stored)
177
atrial peptides
- synthesized in the atrial cells of the heart
- increased blood volume -> increased atrial stretch -> myocardial cells stretch and release ANPs -> natriuretic peptides -> natriuretic peptides target the kidney
- absorbed into coronary vasculature
178
natriuretic peptides
- act on the kidney -> afferent arterioles dilate -> increase GFR and decrease renin -> increase in NaCl and H2O excretion -> blood volume decrease -> blood pressure decrease
- Atrial natriuretic peptides are synthesized in advance and stored in cardiac muscle cells.
- An increase in blood volume is an important stimulus for the release of atrial natriuretic peptides from cardiac muscle cells.
179
The leakage of serum albumin into bowmans capsule would increase GFR
-true
| -
180
look this up in friday lecture :,( 10/30
- pressure in the glomerular capsule is opposed by colloid osmotic pressure and hydrostatic pressure in bowmans capsule
- when there is high hydrostatic pressure and colloid osmotic pressure the force pushing fluid into bowmans capsule will reduce
- serum albumin accounts for most of colloid osmotic pressure -> water will follow
- if hydrostatic pressure and colloid osmotic pressure increase so will
181
vasodilation dilation will decrease GFR
- true
- if exit is "easy" pressure drops
- low pressure leads to a decrease in GFR
182
tubuloglomerular feedback relies upon hormones
- false
- paracrine factors are local and not in the blood -> not a hormone
- paracrine factors travel in interstitial fluid
183
vasopressin binds to vasopressin receptors on cells of collecting duct and initiates a signaling cascade that uses cAMP. the increase in cAMP causes the aquaporin to change from closed to open state.
- false
- vesicles undergo exocytosis in response to cAMP
- nothing to do with open and closed state
- aquaporins are like pores
184
Elastic recoil of the lungs increases intra-alveolar pressure until it is greater than atmospheric pressure during expiration
true
185
The P50 value of hemoglobin in pulmonary veins is less than the P50 value of hemoglobin in capillaries of an active skeletal muscle
true
| -PO2 is lower in capillaries -> higher affinity
186
The tracheal system of insects transports respiratory gases (O2 and CO2) and nutrients dissolved in hemolymph.
false
