Week 4 FC Flashcards
Upper Respiratory Tract
Nose
Pharynx
Lower Respiratory Tract
Larynx
Trachea
Bronchi
Lungs
Conducting Portion of the Respiratory System
Nose
Pharynx
Larynx
Trachea
Bronchi
Bronchioles
Terminal Bronchioles
Respiratory Portion of the Respiratory Tract
Respiratory bronchiole
alveolar duct
alveoli sac
alveoli
Inhalation is ____. Exhalation is _____.
Active
Passive
Most important muscle of inhalation
Diaphragm
Inhalation is the contraction of _____ & _____.
Diaphragm
External Intercostals
Responsible for 75% of air entering the lungs during normal breathing
Diaphragm
When contracted, the diaphragm _________.
Flattens, lowering the dome when contracted (inhalation)
________ muscles are used for deep forceful inhalation
Accessory
When contracted, the External Intercostals ______.
elevate the ribs
Responsible for 25% of air entering the lungs during normal breathing
External Intercostals
2 Things involved in inspiration
-contraction of diaphragm (flattens)
-contraction of the external intercostals (elevates ribs)
As lung volume increases, ____ pressure drops.
Alveolar Pressure/ Intrapulmonic Pressure
As lung volume _____, Alveolar pressure ______.
Increases
Decreases
During _____, pressure in the lungs is greater than atmospheric pressure.
Exhalation
Exhalation is ____, as the muscles _____ instead of ____.
Passive
Relax
Contract
During Exhalation, the diaphragm relaxes & becomes ____shaped. The External Intercostals relax & _____.
dome
drop the ribs down
Exhalation is ____ during forceful breathing out
Active when forceful
Exhalation is passive due to ________.
Elastic recoil of the chest wall and lungs via elastic fibers & surface tension of alveolar fluid.
The lungs contain _____ fibers
Elastic
3 things involved in Exhalation
-elastic recoil of chest wall & lungs
-diaphragm relaxes & becomes dome shaped
-external intercostals relax & ribs drop down
True Ribs
1-7
Attached to the sternum Anteriorly
False Ribs
8-10
Attached to the cartilage of the 7th rib Anteriorly
Floating Ribs
11-12
Costal cartilage
connects ribs to the sternum
thoracic wall shape, structure & function
conical shaped
bony, cartilaginous skeleton
protects thoracic & abdominal organs
Thoracic wall Boundaries
Superior- Thoracic inlet
Inferior- Diaphragm
Lateral- ribs
Anterior- manubrium & Sternum
Posterior- Thoracic vertebrae
Olfaction
smell
Olfaction is possible through the presence of _____ _____ in the superior 1/3 of the nasal cavity
olfactory mucosa
The olfactory mucosa is located in the _________ of the nasal cavity
superior 1/3 of the nasal cavity
CN I
Olfactory Cranial Nerve 1
Where is the Olfactory Bulb located
The Olfactory bulb is located in the Ethmoid bone and has Hair-like projections from CN I that pass from the cranial cavity through holes in the Ethmoid bone known as the Cribiform plate.
What is the route of scent to the Olfactory Nerve (CN 1)
Smells are trapped in the mucous layer below the olfactory bulb in the nasal cavity. Smell travels from cilia in the mucous layer to olfactory receptors in the olfactory epithelium, up the axons of the olfactory nerve into the brain.
Numerous _____ exist in the bones that surround the nasal cavities.
sinuses
The paranasal sinuses function to _________.
Condition & moisten the air we breathe
The paranasal sinuses are ____ at birth and ____ in size until puberty.
small
increase
The paranasal sinuses act to __________ & increase _______ of the voice.
lighten the skull
resonance
The Frontal sinuses lie ____ the eye sockets & the Maxillary sinuses lie ____ the eye sockets.
above
below
The ____ may be sites prone to infection
paranasal sinuses
Roof of the nasal cavity
Anterior >Posterior
Nasal>Frontal>Ethmoid>Sphenoid bones
Floor of the nasal cavity
Maxilla & palatine bone
Medial of the nasal cavity
Anterior >Posterior
Septal cartilage>Vomer>Ethmoid bones
The Lateral nasal cavity is made up of 3 nasal conchae
Superior conchae
Middle conchae
Inferior conchae
The 3 nasal conchae curve downwards to form ____.
meatuses
The ethmoid air cells and maxillary sinuses are located ______.
behind the 3 conchae
The pharynx begins at the ________ and extends to the ______.
internal nares
cricoid cartilage of the larynx
deglutition
swallowing
The contraction of skeletal muscles surrounding the ____ assist in deglutition (swallowing)
pharynx
regions of the pharynx
nasopharynx
oropharynx
laryngopharynx
functions of the pharynx
-Passageway for air & food
-Resonating chamber
-houses the tonsils
respiratory passage between the Pharynx & Trachea
Larynx
The thyroid gland is located ____ to the pharynx & the esophagus is located ____ to the pharynx.
Anteriorly
Posteriorly
The Larynx is formed by the _____ cartilages of the _____, ______, & _______ and the _____ cartilages–the ____.
Unpaired cartilages
thyroid
cricoid
epiglottis
paired cartilages
arytenoids
What are the unpaired cartilages that make up the larynx?
What are the paired cartilages that make up the larynx?
Unpaired:
Thyroid
Cricoid
Epiglottis
Paired:
Arytenoids
The cartilages that make up the larynx are connected by
joints, membranes, ligaments
The larynx is the ___.
Vocal Fold (True Vocal Chords)
Extends from the Larynx to the superior border of T5
Trachea
The trachea divides into the _____ & ______.
Left & Right Primary Bronchi
layers of the trachea
mucosa (inner)
submucosa
hyaline cartilage (16-20 c-shaped rings)
adventitia (outer)
The trachea is composed of ________ of hyaline cartilage
16-20 C shaped rings of hyaline cartilage
The esophagus sits ____ to the trachea
Posteriorly (behind)
Internal ridge of the bronchial tree
carina
most sensitive area for triggering cough reflex
carina
The bronchial tree Superior to Inferior
Right & Left Primary Bronchus
Secondary bronci (one in each lobe)
Tertiary bronchi
bronchioles
terminal bronchioles
respiratory bronchioles
alveolar ducts
What are the structural changes that occur with branching of the bronchial tree
-mucous membrane becomes thinner the farther down you go
-incomplete rings becomes plates, then disappear
-as cartilage decreases, smooth muscle increases
How does the SNS affect the bronchial tree?
PNS?
SNS= relaxation/dilation
PNS= contraction/constriction
The lungs are separated from each other by the ___ and other structures in the ____.
heart
mediastinum
Each lung is enclosed by a __________.
double-layered pleural membrane
-Parietal pleura (outer)
-Visceral pleura (inner)
The parietal pleura of the lung _______.
The visceral pleura of the lung _______.
lines the wall of the thoracic cavity
covers the lungs themselves
Pleural cavity of the lungs
between the Parietal pleura & Visceral pleura
The pleural fluid of the lungs reduces _____ & produces _______ (stick together)
friction
surface tension
Where is the cardiac notch located?
left lung
the ______ makes the left lung 10% smaller than the right lung
cardiac notch
Right lung has ___ lobes
Left lung has ___ lobes
3 Right
2 Left
The lobes of each lung are divided by _____.
fissures
The right lung has ___ fissures, the Left lung has ___ fissures.
2 fissures (Horizontal & Oblique fissure)
1 fissure (Oblique fissure)
Fissures of the Right Lung
Horizontal fissure (upper portion, runs horizontally)
Oblique fissure (splits the 2nd & 3rd lobe)
Lobules of the lung are wrapped in ______ connective tissue, contain a ________, ________, & _________.
elastic
lymphatic vessel
arteriole
venule
Alveoli are ___ shaped outpouchings. The alveolar sac is composed of ___ alveoli sharing a common opening.
cup
2
Types of alveolar cells
Type I
Type II
Type 1 alveolar cells
vs
Type II alveolar cells
Type I
-nearly continuous lining
-more numerous
main site of gas exchange
-thin, squamous cells
Type II
-septal cells
-contain microvilli
-secrete alveolar fluid (Surfactant)
-cuboidal cells
Surfactant function
reduces tendency of alveoli to collapse
Bonds between AAs
peptide bonds
peptide bonds form a ____.
dipole
Repetitive peptide bonds allow for the formation of repetitive ____ bonds & the formation of _____ structures.
H+
secondary
Polypeptide AA chains are always in the ____ configuration
Trans (Up/Down/Up)
H+ are Hydrogen bond _____.
O is a Hydrogen bond _____
acceptor
donor
secondary structures
alpha-helices
beta-sheets (also, the beta turns connect sheets together)
The alpha-helix structure is stabilized by _______ bonding while the AA side chains are oriented _________.
repetitve hydrogen bonding
to the side of the helix (sticking out)
The beta-sheet structure is stabilized by ____ bonding, while the AA side chains are oriented _______.
repetitive hydrogen bonding
above and below the plane of the beta-sheet
Tertiary structure is stabilized by ______ between atoms comprising the side chains of AAs, enabling folds & shapes to form.
interactions
Quaternary structure occurs when ____ polypeptides associate together to create a new, higher-order structure.
2 or more
Fibrous protein example
Collagen
silk
keratin
Collagen is a tightly wound _____ of proteins & is not composed of ______ & is not a _____ protein.
-Triple helix
-alpha-helices
-globular
Most abundant protein in humans.
collagen
Where can collagen be found?
bone
skin
ligaments
part of connective tissues
Water soluble proteins assume an approximately _____ shape and are characterized by having ____ AA side chains on the surface, ____ AA side chains in the interior, a variety of _____ structures and have _____ function.
spherical
polar (for water solubility)
nonpolar (for hydrophobic core)
secondary (a-helices, b-sheets, turns)
metabolic/biological (catalytic, regulatory, transport)
Water soluble proteins often have biological or metabolic roles such as
catalytic
regulatory
transport
Prosethic group
a non-protein component found on some proteins
Ex: In Mb & Hb, the prosthetic group is Heme
Allosteric
Other site
Orthosteric
Same site
Strong forces of molecular attraction
Covalent bonds
Polar covalent bonds
Weak forces of molecular attraction
Ion-Dipole attraction
Hydrogen bonding
Dipole/Dipole attractive force
Van Der Walls Force
Hydrophobic effect
Porphyrin Ring structure
Cyclic tetrapyrrole ring structure
The Porphyrin Ring is assembled from
-AAs (containing Nitrogen)
-TCA cycle intermediates
Heme is a ______ with ____ in the center
porphyrin ring
Ferrous (Iron) Ion
Globular heme proteins contain heme as their _______.
prosthetic group
Ferrous ion (Iron) can form ___ coordinate covalent bonds.
6
Almost all cells in the body have ______ containing proteins
Heme
Globular heme protein Functions
-May be found as part of an enzyme Active site
(cytochrome p450 enzymes in Liver)
-Transport O2
(Hb in RBCs)
-Store O2
(Myoglobin in muscle cells)
-Electron carriers
(required for mitochondrial ETC)
Oxygen is stored by _____ in ______ cells
Myoglobin
muscle
The globin protein monomer is mostly composed of _____ and has NO _____. A few bends or turns are present.
alpha-helices
beta-sheets
Most proteins are a combination of ____ & ____.
alpha-helices & beta-sheets
Myoglobin Structure
Myoglobin Structure (2)
Ferrous Iron (Fe2+) forms 6 covalent bonds. ___ bonds form to the Nitrogen atoms of the Porphyrin ring. ___ bonds link to the globin protein. ____ bonds are free to reversibly bind Oxygen.
4
1
1
The ferrous Iron Ion is protected by the ______, and buried deep inside the _____ protein. WHY?
porphyrin ring
globin
-Helps to ensure that O2 is released as O2 & not another oxide species
-O2 entry & exit is in a defined path through the globin protein
Myoglobin is designed to store ___ in the cell & deliver to the ___ when needed.
Oxygen
Mitochondria (muscle)
The myoglobin Dissociation curve is a ____ curve.
Hyperbolic (“r” shaped)
The primary sequence of Myoglobin is _____ than Hemoglobin. However, the _____ of important AAs ensures correct shape.
Hemoglobin
conservation
Hemoglobin is a ______ of 4 polypeptide chains. Hemoglobin A (HbA) is made up of a pair of identical _____.
tetramer
alpha-beta dimers
In hemoglobin, the heme groups are ____ spaced. Access to the Fe2+ ion is through a _____ in the protein.
widely
channel
What types of interactions can be found throughout/ between the Hemoglobin subunits?
-Hydrophobic
-ionic
-hydrogen bonding
How many oxygen molecules can be carried on 1 Hemoglobin molecule?
4 Oxygens
-1 on each globin monomer
Hemoglobin A (HbA) is also called an _____.
a2B2 tetramer
The alpha-Beta peptides that form a dimer are held together very ______. They don’t change, they stay ____ linked together. The 2 dimers associate with each other, but may ____ slightly. This structural change is how O2 affinity is ______.
tightly
tightly
shift
regulated
Between alphaBeta dimers of Hemoglobin, there are few _______ bonds, ________bonds, and ______. However, there are Many ______ between aB peptides to form strong dimers.
hydrogen bonds
ion-dipole bonds
ionic interactions
Hydrophobic interactions
As Hb binds Oxygen, some ____ bonds are broken
Hydrogen
Histidine contains a _____ structure as its side chain
Imidazole
Histidine with an Imidazole Ring
____ is the only AA with an ionizable side chain whose ___ is close to physiological pH
Histidine
pKa
The Histidine (& Imidazole ring) allows Hb to
-buffer the pH of Blood
-Regulate O2 affinity in response to pH
The side chain of Histidine has a ______ group that has a pKa in a physiologically useful range
weak acid/base
-The H+ ion is protonated when pH drops & Removed when the pH rises
The side chains of ____ & _____ may contribute a Hydroxyl group at the interface between the aB dimers of Hb.
Serine
Threonine
The side chains of ___ & ____ may contribute positive charges.
Lysine
Arginine
The various side chains of AAs found in Hb dimers can participate in H+ bonding, ion-dipole interactions, or ionic interactions which can affect the ____ of oxygen binding.
affinity
The side chains of ___ & ____ may contribute negative charges.
Aspartate
Glutamate
The side chains of ___ & ____ may contribute an amide functional group.
Aspargine
Glutamine
The more equivalents of OH- (Hydroxyl) you add, the ___ the H+ in solution, and the ____ the pH
lower
higher
OH- is a H+ acceptor (makes pH more Alkaline)
AAs whose side chains may stabilize the hydrophobic interactions of the globin aB-dimers
Branched-chain AAs
-valine
-leucine
-isoleucine
Aromatic side chain AAs
-phenylalanine
-tyrosine
-tryptophan
AAs with Hydrophobic side chains
-Methionine
-Proline
-Glycine
-Alanine
The porphyrin ring in Heme is not always ____
perfectly planar
When the Heme is deoxygenated, it is ____ shaped. When the Heme is oxygenated, it is ____ shaped.
non-planar, dome shaped
Planar, straight across as the O2 pulls down the proximal histidine.
As O2 binds to the heme, it tugs on the a-helix, which causes the shape of the monomer to change, signaling to the other subunits that it has been oxygenated. The binding of 1 O2 molecule ____ binding of another O2 molecule, known as _____ _____ binding.
promotes
cooperative ligand binding
O2 is a __________ regulator of oxygen binding, because O2 binding at one site _____ affinity for O2 at another site.
Positive Allosteric Regulator
Increases
Cooperative ligand binding creates a _____ curve when affinity/saturation is plotted against partial pressure.
Signmoidal curve “s”
Myoglobin stores Oxygen in the ____. While Hemoglobin delivers Oxygen to the ____.
Muscles
Tissues
Myoglobin has a ____ affinity for oxygen than Hemoglobin, as it has to obtain the O2 from the Hb.
Higher
At pH 7.4, the p50 of Hb is ____mmHg and changes with pH. The pH of Mg is ___mmHg & does NOT change with pH.
p50=pressure when 50% O2 binding sites are saturated.
26mmHg
1mmHg
The O2 dissociation curve shifts to the ___ when pH decreases, as O2 has a ____ affinity for binding. The O2 dissociation curve shifts to the ____ when pH increases.
Right (acidic)
Decreased affinity
Left (alkaline)
Increased affinity
The pH is ___ in tissues with active metabolism because CO2 is produced.
Reduced
Histidine side chains are more likely to be ____ when pH is LOW because there are more H+ molecules available. These extra charges allow more ionic interactions between dimers & creates a ______ for Hb to assume the taut shape, which ____ the affinity for Hb to hold onto O2, which ____ O2 delivery to tissues that are actively metabolizing (or exercising muscle).
Charged
Driving Force
decreases
increases
____ promotes the formation of Carbonic Acid from CO2. Carbonic Acid can then be turned into Bicarbonate (HCO3-)
Carbonic Anhydrase
CO2>Carbonic Acid (via Carbonic Anhydrase) is spontaneously ___, but not fast enough to support life. Carbonic anhydrase speeds up the process.
fast
When CO2 is converted into Carbonic Acid via Carbonic Anhydrase what occurs in Hb & O2 delivery?
-The H+ ions protonate Hb (+ charges)
-Allows formation of additional salt bridges
-Stabilizes the taut form of Hb
-Promotes O2 delivery to the tissues
CO2 can react with the _____ terminus of the _____-chains of Hb. This allows the formation of salt bridges and the release of ___.
Amino terminus
alpha chains
H+ ions
Hb can carry some ____, but the ___ does NOT bind to the iron in the heme. It binds to the ___ terminus of the alpha globin chains.
CO2
CO2
N-terminus
Reduced pH & Increased H+ ions allows the formation of more charged sites on Histidine side chains and more salt bridges to exist.
True
The Bohr effect does not work without ______ as it is a potent regulator of Hb ____ affinity.
2,3 BPG
Oxygen
2,3 BPG is a ____ charged molecule and it is very ____ in size.
negatively
small
The positively charged side chains of AAs in Hb form a pocket for ____ to bind between the Bsheets of deoxyhemoglobin.
2,3 BPG
Heme is covalently attached to the ____ histidine and is locked into a _____ pocket of the globin fold.
proximal
hydrophobic
____ promotes the formation of the Taut state of Hb and ____ O2 affinity for Hb
2,3 BPG
decreases
2,3 BPG allows the formation of additional _____ between the aB dimers, creating a driving force for Hb to assume the ____ form & promote the _____ of O2 into tissues.
salt bridges
Taut
unloading
____ decreases the affinity of Hb for O2 and _____ release of O2 to the tissues
2,3 BPG
promotes
2,3 BPG is a _____.
Negative Allosteric Effector
When 2,3 BPG increases, the dissociation curve shifts ____. When it decreases, the curve shifts ____.
Right (Lower affinity for O2 binding to Hb)
Left (Higher affinity for O2 binding to Hb)
At high altitudes an individual will have ____ levels of 2,3 BPG which will shift the dissociation curve ____, promoting the release of O2 into the tissues.
Higher
Right
Regulation of O2 delivery by Hb depends on _____ effectors such as _____.
Allosteric effectors
-pO2 (more O2=more O2 loading)
-pH (low pH=less O2 binding; high pH=more O2 binding)
-pCO2 (influences pH)
-2,3 BPG
O2 affinity should be higher in what tissues?
O2 affinity should be lower in what tissues?
The lungs (where O2 needs to Load)
All other tissues (where O2 needs to Unload)
Which tissues will have a higher pH?
Lower pH?
Lungs (CO2)
Metabolically active tissues
Increased ___ creates a Right shift.
temperature (exercising muscles generate heat, signal that the more O2 is Needing to be released into the tissues)
The ____ have a dominant role in maintaining homeostasis.
kidneys
The kidneys have ____ blood flow & receive ____% of the cardiac output, or ___ L/min
High
20%
1.2 L/min
Kidneys functions
-filtration of blood
-regulate blood volume & composition
-regulate BP
-synthesis of glucose & vitamin D
-release Erythropoietin
-excrete waste (urea, uric acid, creatinine, drugs, foreign compounds)
-transport, store, & discharge urine
The kidney is located _____, closely pressed to the posterior abdominal wall. At the vertebral level of ___-___.
retroperitoneal
T12-L3
_____ cap the the kidneys superiorly.
suprarenal gland/ adrenal glands
Layers covering the kidneys (inner>outer) and their functions
Renal capsule (protective)
Perinephric adipose (cushion)
Renal fascia (protective)
Pararenal fat (adipose layer)
port for transmission of neurovascular structures & ureter
Hilium
peripheral area of the kidney, lighter on color
cortex
Deeper, darker-colored region of the kidney. Pyramid shape
medulla
part of the cortex extending between renal pyramids
renal column
the cortex of the kidney is ____ in appearance as it has abundant _____ & _____.
granular
renal corpuscules
convoluted tubules
The cortex contains ____ & _____ nephrons
cortical
Juxtamedullary
The ___ of the medulla is where collecting ducts converge
apex (renal papilla)
The medulla is ____ in appearance due to an abundance of ________tubules.
striated
straight
Functional unit of the kidney
nephron
The parenchyma contains
-nephrons
-lobes
-lobules
The lobes of the kidney contain
cortex
medulla
1/2 of the adjacent renal column
Lobules of the kidney are located in the ____.
cortex
renal pelvis function
collects urine from the major & minor calyces
fat-filled cavity surrounding the calyces & renal pelvis
renal sinus
The kidneys receive ~_____ of the cardiac output every minute
20-25% or 1200mL
Route of blood flow through the kidney
-afferent arterioles take blood to the glomerulus in the renal cortex to be filtered
-blood leaves the glomerulus through efferent arterioles
-blood flows from the efferent arterioles into the peritubular arteries (cortical nephrons) or the vasa recta (juxtamedullary nephrons)
Arteries of the kidney (in order)
Renal artery
segmental artery
interlobar artery
arcuate artery
Major vein of the kidney
Renal vein
____ nephrons are located within the cortex, ____ nephrons are located within the medulla
cortical nephrons
juxtamedullary nephrons
Cortical nephrons are more ____ than juxtamedullary nephrons & they lack a ______.
abundant
thin ascending limb
Parts of a nephron & function
-renal corpuscles (filters plasma)
-tubules (filtered fluid passes through)
The collecting system is composed of the
-cortical collecting ducts
-medullary collecting ducts
There are ___ juxtamedullary nephrons. They contain ______ which are located in the inner cortex near the medulla. Their Loop of Henle is ___ & extends ___ into the medulla.
Few
renal corpuscules
long
deep
The _____ is a network of capillaries
glomerulus
Filtered fluid from the glomerulus collects in the glomerular capsule between the _____ & ____ walls.
visceral
parietal
glomerular capsule structure
double-walled cuplike structure lined by epithelium and podocytes
Mesangial cells location & functions
-located between podocytes
-have a role in cleaning debris, vascular responses, deposit of matrix
MD= macula densa
PCT= proximal convoluted tubule
The glomerulus is made up of ____ capillaries
fenestrated capillaries
Layers of the glomerulus
-fenestrations of the glomerular endothelial cells
-basement membrane
-pedicels
-podocytes-filtration slits between pedicels
Juxtaglomerular apparatus function in the kidneys
Regulate blood pressure
The ____ arteriole of the glomerulus has ____ detectors that detect ________ flowing into the glomerulus.
afferent
stretch detectors
drops in blood pressure
The ____ detects decreases in Sodium concentrations in tubular fluid and stimulates the Juxtaglomerular cells to release ____.
Macula densa
Renin
Route of urine leaving the kidneys
minor calyx
major calyx
renal pelvis
ureter
the minor calyx are ___ shaped ____ areas
funnel shaped
collecting areas
____ contractions of the ureters pushes urine through the ureters to the urinary bladder.
peristaltic
Layers of the ureter
mucosa (inner)
smooth muscle (3 layers: inner longitudinal, middle circular, outer longitudinal)
adventitia (outer)
Constrictions of the ureters
-the Ureteropelvic junction
-the Pelvic Brim
-the Ureterovesical junction
The bladder has a capacity of ~____mL
700-800mL
Trigone of the bladder
-left ureter
-right ureter
-urethra at the apex
Bladder layers
-mucosa
-detrusor muscle (3 layers: inner longitudinal, middle circular, outer longitudinal)
-Adventitia/Serosa
Sphincters of the bladder & location
Internal Urethral Sphincter (superior)
Sphincter Urethrae (Inferior)
The bladder is made up of _____ epithelium which allows it to _____.
transitional epithelium
stretch
Male vs Female urethra
Male:
-20cm long
Female:
-4cm long
3 regions of Male urethra
-prostatic urethra (internal urethral sphincter)
-membranous urethra (external urethral sphincter)
-spongy urethra
The prostatic urethra of the male forms the _____ sphincter & also serves to receive secretions from the ______ & ______.
internal urethral sphincter
seminal vesicles
ductus deferens
Female urethra cell composition from inner portion to external portion
inner: transition epithelium
middle: stratified or pseudo-stratified columnar epithelium
end: stratified squamous epithelium
At pH 7.0 ___ ions = ____
H+ = OH-
Basic/Alkaline vs Acidic
Alkaline: High H+ Low OH-
Acidic: Low H+ High OH-
Strong Acids
HCl Hydrogen chloride
HBr Hydrogen Bromide
HI Hydrogen Iodide
HNO3 Nitric Acid
HClO4 Perchloric Acid
H2SO4 Sulfuric Acid
Strong acids react in water to ____ H+ (protons)
Donate H+ (make pH lower)
Strong bases react in water to ____ H+ protons
accept H+ /donate OH- (make pH higher)
Strong bases
LiOH (Lithium Hydroxide)
NaOH (Sodium Hydroxide)
KOH (Potassium Hydroxide)
BaOH2 (Barium Hydroxide)
MgOH2 (Magnesium Hydroxide)
ic/oic = ____
ate= ____
Acid (may donate H+)
Base (can accept H+)
Weak acids have a ___ pKa value.
Strong acids have a ___ pKa value.
The ___ the Ka, the ____ the acid.
The ___ the Ka, the ___ the acid.
positive >0
negative <0
Higher, stronger
Lower, weaker
When pH of the solution is equal to the pKa of the weak acid, there are ____ amounts of the weak acid and its conjugate base, so it is ____% dissociated
equivalent
50%
Buffering region
-where pH changes slowly as H+ or OH- is added
-acid or base may be added but pH won’t change much
-Buffering range for a weak acid is +/- 1 of the pKa
-The buffering region is defined as the pH range where the weak acid and its conjugate base exist at similar (it doesn’t have to be equal) concentrations
Buffer definition
-When a weak acid and a similar amount of its conjugate base are mixed, a buffer is formed.
-Buffers resist a change in pH
what determines the structure of liquid water?
Hydrogen bonds
H2O with 4 bonds is ____
H2O with 3.5 bonds is ____
Ice
Liquid H2O (H bonds are constantly changing)
____ is responsible for the thermal properties of H2O, such as a ____ melting point due to a High __________ and H2O has a ____ boiling point due to a high ______.
Hydrogen bonds
Low melting point
High heat of fusion
High boiling point
High heat of vaporization
Water has a ____ range for the liquid state
large temperature range (0-100 C)
Water molecules ____ heat very quickly (conductivity). Since energy put into H2O affects H+ bonds first, temperature changes very ____ giving it a high _______.
equilibrate
slowly
heat capacity
_____ allows water to dissolve polar substances, like Chloride & Sodium.
Hydrogen bonds
Water can self _____ into Hydronium (H3O+) & Hydroxide (OH-)
dissociate
pH is a way to describe the concentration of ____ in water solution
H+
____ acids completely dissociate in water
Strong acids
HA –(water)-> H+ + A-
___ describes the equilibria of water dissociation
kw (constant) 10^-14
Graph of the Titration of a strong Acid by a strong Base
____ acids do NOT dissociate completly
weak acids
Acetic acid is a ______ acid
Monoprotic weak acid
Only a small fraction of ____ acid actually dissociates in water, most acetic acid stays in the acid form, due to low Ka values.
weak
weak acids have Ka values that have exponents with ____ numbers (extremely _____). Strong acids will have Ka values that have exponents with ____ numbers (extremely _____).
negative
small #s
positive
Large #s
____ refers to the extenet of proton dissociation and is measured by the value ____ or ____. (How good it is at donating its H+)
Strength
pKa or Ka
Strong acid Ka is ____ & pKA is _____.
Weak Acid Ka is _____
very very large, very very small
measurable, larger than pKa of a strong acid
_____ refers to the amount of dissolved substance (molarity)
concentration
____ acids can be toxic when concentrated
weak. Danger is not always related to acidity strength.
-logH+=
-logKa=
-logH+=pH
-logKa=pKa
3 major buffers
CO2/HCO3-
Proteins
Phosphate
____ may act as a buffer when in a protein (Hemoglobin)
Histidine
Nitrogen waste disposal types
Ammonotelic- NH4 Ammonium release
Ureotelic- Urea (in urine)
Urease- urea>NH3 + HCO3-
Uricotelic- Uric acid secretion (purines)
Uric Acid- in humans from purine degradation
ammonia NH3 is in equilibrium with
ammonium NH4+ so ammonia may freely
diffuse across membranes.
True
____ is not charged and has no acid base activity.
Urea
Places Nitrogen comes from
-protein turnover
-AAs
-Purine & Prymidine synthesis
-Porphyrins- heme
-specialized Nitrogen products (creatine, melanin)
There is ___ storage form of Nitrogen in the body.
NO
The urea cycle is very active during the ___ state
fasting
During the fasting state, what events occur leading up to the Urea cycle?
- Body protein is degraded
- AAs flood into the blood
- AAs go the liver
- NH3 groups are removed
- This releases the alpha-keto acid skeletons from the amino acid to help
support energy needs for body during the fasting state - Keto acids carbon skeletons are converted into glucose (gluconeogenesis) * Or ketone bodies (ketogenesis)
- NH3 must be detoxified
- Urea cycle
The ____ group must be removed for an AA to enter catabolism
Amino
end fate for NH4+ Ammonium
The Urea cycle
What occurs to AAs when they enter the Urea Cycle?
-The amino group is taken off and
transferred to alpha-KG to form glutamate (in the liver)
* The idea: collection of the N group into glutamate
* Reaction: transamination with a-KG
* Results in: Formation of glutamate & a-keto acid
* Later, glutamate can release the N as free ammonia and the urea cycle will detoxify it
a-keto acid
carboxyl group and a ketone coming off the alpha-carbon
Transamination Reaction
- Reversible exchange of NH3
group from an amino acid to
an α-keto acid - All TA reactions are freely
reversible - Typically, glutamate & a-KG
are always one-half of the
transaminase reaction - The ΔG is ~ 0 * So, the directionality of the reaction is dependent on [concentration] of substrates
A transaminase reaction is ______
the reversible exchange of NH3 from an AA to an a-keto group
All transaminase reactions are freely ____. The delta G (change in energy) is ___. The directionality of the reaction is dependent on the ____ of the substrates.
reversible
0
concentrations
Goal of most Transaminase reactions
Collect Nitrogen in Glutamate for eventual disposal in the urea cycle
NH3 is removed from Glutamate using
glutamate dehydrogenase
The body may deliver excess ____ to the liver via _____
nitrogen
glutamine
Glutamine contains ___ nitrogens
Glutamate contains ___ nitrogens
2
1
Glutamine can release ___ Nitrogens for detoxification into the Urea cycle. How are they removed?
2
First N= Glutaminase reaction
2nd N= Glutamate dehydrogenase RXN
____ is the most important Nitrogen carrier in the blood
Glutamine
Excess Nitrogen from the body is transported in the blood as ____, like ____.
AAs
Glutamine (2 N)
Glutamate (1 N)
Release of NH3 from glutamine>glutamate
Glutamine (in blood & tissues)
travels to LIVER & kidneys
glutaminase synthetase (release 1 N)
Glutamate
glutamate dehydrogenase (release 1 N + aKG)
-oxidative deamination in the liver
-regeneration of aKG
3 enzymes that catalyze reactions that fix free NH4+ into organic molecules
-glutamate dehydrogenase
-glutamine synthetase
-carbamoyl phosphate synthetase 1
Glutamate dehydrogenase is freely ____, and can liberate to incorporate free NH3.
reversible
Ammonia is converted to urea in the ____. Then released into the ____, carried to the ____ to be filtered and excreted in the ____.
Liver
blood
kidneys
urine
In the liver, ammonia formation (and α-KG) is the ____ direction of this reversible reaction because the ammonia can be delivered to the ______ for non-toxic disposal
predominant
urea cycle
NH3 may also be released in the ____, under conditions like metabolic acidosis where it will act to buffer the urinary pH.
urine
The urea cycle is located exclusively in the ____. The first 2 RNXs occur in the _____ and the last 3 RXNs occur in the _____.
Liver
mitochondrial matrix
cytosol
Urea Cycle Steps
NH4 + HCO3- + 2ATP
Carbamoyl phosphate (rate limiting & reg)
Carbamoyl phosphate + Ornithine
(ornithine transcarbamoylase)
Citrulline
Citrulline + Aspartate
(Arginosuccinate synthetase)
Arginosuccinate
(Arginosuccinate lyase)
Fumarate OR Arginine
Arginine
(Arginase)
Urea (diffuses to the blood, transported to kidneys, excreted in urine)
What is the 1 exception to the rule that transaminases funnel Nitrogen groups into Glutamate?
Aspartate aminotransferase
-The AST reaction has a net flux towards aspartate.
-This allows Aspartate to always have a high enough concentration for delivery of the 2nd Nitrogen (ammonia) into the Urea cycle.
The feed-forward mechanism regulating the Urea cycle is dependant on the concentrations of ____ & ____ to form N-Acetylglutamate (NAG).
Glutamate
Arginine
Positive feed-forward regulation of the Urea Cycle is dependent on
-concentration of Glutamate & Arginine
-rate of NH4+ production
-increase in protein metabolism (fasting state & high-protein diet)
Net reaction of Urea Cycle
NH4+ + CO2 + 3ATP + Aspartate
>Urea + Fumarate + 2ADP + 2Pi + AMP +PPi
-The first N of urea comes from ___
-The 2nd N of urea comes from ___
-____ is needed to supply both^
-Consumption of ___ ensures that the cycle doesn’t turn backwards.
NH4+
Aspartate
Glutamate
ATP
Urea diffues out of the _____ of the Liver and is transported in the ____ to the ____ and excreted in the ____.
hepatocytes
blood
kidneys
urine
Hyperammonium can be caused by a metabolic deficiency of ____ of the 5 urea cycle pathway enzymes or NAG synthase. Any substrates before that block will ____.
Any
accumulate
Symptoms of hyperammonemia
vomiting
irritability
cognitive impairment
lethargy
blurred vision
-can be lethal if prolonged
Secondary hyperammonemia can be caused by ____ or _____, such as ___, ____, or ____. All lead to an increase in NH3 in the blood and can be ____.
liver disease
liver damage
hepatitis
hepatotoxins
cirrhosis
toxic
The ____ enzyme in the hepatic portal vein releases ammonia. If the hepatocytes are not fully functional, ammonia will enter systemic circulation.
urease
When aKG is converted to Glutamate during the urea cycle, this results in ____ TCA cycle activity which therefore ___ ATP synthesis.
decreased
decreases
2 reasons why ammonia has toxic effects
-aKG is converted to Glutamate>decreases TCA>decreases ATP
-Altered balance of Neurotransmitters in brain
Glutamate>glutamine>Reduced glutamate levels=reduced GABA levels>excess excitatory signals by Glutamine decreased inhibitory signals by GABA & decreased excitatory signals by Glutamate
Kidney functions
-producing urine
-controlling blood pressure, blood flow, & blood constituents
-filtering & cleaning blood
-synthesizing & secreting Renin, Erythropoietin, Vitamin D 1,25DH
2 components that determine flux across the glomerulus
-permeability (size & charge)
-small molecules <15A freely filtered
- >35A no filterability at all
- cations (+) > Neutral > Anions (-)
-glomerular filtration pressure
Starling forces
4 pressures affecting fluid movement across the capillary wall
1-Hydrostatic pressure of capillary
2-Hydrostatic pressure of interstitium
3-Oncotic pressure of blood plasma
4-Oncotic pressure of interstitial fluid/Bowman’s space
Hydrostatic pressures ____________ while oncotic pressures ______________.
-push H2O away/ out of capillary/interstitium
-proteins drawing H2O IN capillary/interstitium
Hydrostatic pressure of capillary ____ filtration. Hydrostatic pressure of interstitium _____ filtration & _____ reabsorption. Oncotic pressure of blood plasma ____ filtration & ___ reabsorption. Oncotic pressure of interstitial fluid/Bowman’s space ____ filtration (cations+) ____ proteins allowed in Bowman’s space.
favors
opposes
favors
opposes
favors
favors
NO
PG
PB
pG
pB
PG=Hydrostatic pressure of capillary
PB=Hydrostatic pressure of interstitium
pG=Oncotic pressure of blood plasma
pB=Oncotic pressure of Bowman’s space
Glomerular filtration pressure
deltaP= (PG+pB) - (PB+pG)
Nephrotic syndrome causes _____ permeability of glomerular capillaries to Plasma Proteins and results in _____ oncotic pressure of Bowman’s space
Increased
increased
Urinary Tract obstruction (obstructive uropathy) _____ tubular flow and results in _____ hydrostatic pressure of the interstitium
backs up
increased
Glomerular filtration rate
rate at which the ultrafiltrate forms in Bowman’s space
GFR= Kf(deltaP)
Normal values:
GFR= 90-140ml/min
Kf=10-15ml/min/mmHg (~12)
deltaP=10mmHg
Constrict Afferent=
decrease Renal plasma flow
decrease glomerular hydrostatic pressure
decrease filtration
decrease GFR
Dilate Afferent=
increase Renal plasma flow
increase GFR
Constrict Efferent=
decrease RPF
increase glomerular hydrostatic pressure
increase filtration
Increase GFR
Filtration
Movement of solutes from glomerular capillaries to Bowman’s Space
reabsorption
Returns most filtered solutes to circulation
secretion
Transports solutes from peritubular capillaries and vasa recta into the tubular lumen
excretion
Solute in urine due to filtration, secretion, reabsorption
driving force for reabsorption
Plasma oncotic pressure in peritubular capillary
force that prevents water from
entering capillary
Hydrostatic pressure in peritubular capillary
67% H2O/solutes reabsorbed by the _____ & returned to the bloodstream by peritubular capillaries
Proximal tubule
If GFR is too high= ________
If GFR is too Low= ________
HIGH GFR= Needed substances cannot be reabsorbed quickly enough and are
lost in the urine
LOW GFR= Everything is reabsorbed, including wastes that are normally
disposed
Autoregulation ______ GFR & RBF
maintains constant ~180L/day when MAP is between 80-180mmHg
Myogenic response
increased arterial pressure stretches smooth muscle in blood vessel walls, which induces constriction of the afferent arteriole which:
decrease Renal plasma flow
decrease glomerular hydrostatic pressure
decrease filtration
decrease GFR
Increased BP causes increased afferent arteriole stretch, causes more calcium channels to open, which increases afferent arteriole contraction. This is known as the ____
myogenic response
Tubuloglomerular feedback
Macula densa cells part of juxtaglomerulus apparatus that sense tubular flow and GFR and send feedback signals to afferent or efferent arteriole to constrict/dilate to keep GFR at normal levels
2 key autoregulation of blood flow responses
myogenic response
tubuloglomerular feedback
Normal levels of Na+ in the Extracellular & Intracellular fluid
ECF- 140mEq/L
ICF- 14mEq/L
Sodium plays a role in determining ____ volume>____ volume>____ volume>____.
ECF volume
Plasma volume
blood volume
blood pressure
Daily Na+ intake= _____
daily Na+ excretion
Positive Na+ balance & effects
Negative Na+ balance & effects
Na+ excretion< Na+ intake
increased ECF volume expansion
Increased blood volume
increased BP
Na+ excretion > Na+ intake
ECF volume contraction
decreased blood volume
decreased BP
All of our essential solutes are reabsorbed with Na+. This includes _______
Glucose
AAs
HCO3-
Na+ reabsorption is coupled with ____ molecules such as _____.
_____ mechanisms account for 10% of Na+ reabsorption.
uncharged
glucose
AAs
Phosphates
Lactate
Citrate
Cotransport
The _______ antiport allows H+ secretion for HCO3- reabsorption. This antiproton accounts for ______% of sodium reabsorption.
Na+/H+
20-25%
Early Proximal tubule=
Late Proximal tubule=
Na/HCO3 Reabsorption (cellular component)
NaCl Reabsorption (paracellular component)
In the late proximal tubule, the Na+/H+ antiport is coupled to _____ reabsorption and ____ secretion. This accounts for ____% of Na+ reabsorption.
Cl-
Formate
35%
The late proximal tubule has a ____ component and a ____ component. The 2nd component is responsible for _______.
cellular
paracellular
passive reabsorption of Na+ & Cl-
The thick ascending limb contains the ____ cotransporter for _____ reabsorption and the ___ antiporter for ____ reabsorption. The thick ascending limb accounts for ___% of Na+ reabsorption.
Na+/K+/2Cl- cotransporter
Na+ K+ 2Cl- reabsorption
Na+/H+ antiporter
HCO3- reabsorption
25% Na+ reabsorption
The early distal tubule contains the ___ cotransporter for ___ reabsorption. Accounts for ____% Na+ reabsorption.
Na+/Cl- cotransporter
Na+ & Cl- reabsorption
5% Na+ reabsorption
The late distal tubule & collecting duct contain 2 types of cells: ____ & ____. The ____ cells are involved in Na+ reabsorption & H+ secretion. The ____ cells are involved in K+ reabsorption & H+ secretion. Na+ reabsorption occurs via ____.
Principle cells
alpha-Intercalated cells
Principle cells
alpha-Intercalated cells
Sodium channels/ electrochemical gradient
The Late distal tubule & collecting duct account for ___% of sodium reabsorption. The late distal tubule and collecting duct are hormonally regulated by ____ which synthesizes ____ to increase Na+ reabsorption.
3%
Aldosterone
Na+ channels
% sodium reabsorption in each part of the nephron
Proximal Convoluted tubule= 67%
Thin Descending Loop of Henle
Thin Ascending Loop of Henle
Thick ascending Limb= 25%
Distal Convoluted tubule=5%
Collecting duct=3%
Excretion= <1%
Low BP stimulates ___ secretion from the ____, which stimulates the production of ____, which is converted to ____ by ____ which then stimulates ____ from the _____ to increase ____ & ____ reabsorption in the kidneys.
Renin
Kidneys
ANGI
ANGII
ACE
Aldosterone
Adrenal Cortex
Na+ & H2O
Renin is secreted in the ___ by the ____ cells of the ___ arterioles in response to ___ renal arteriole pressure which catalyzes the conversion of ____ into ANGI.
The macula densa cells located in the ____ tubule stimulate the ____ cells to release ____ in response to decreased ____ concentration in the tubules.
kidneys
juxtaglomerular cells
afferent
Low/decreased
Angiotensinogen
Distal
juxtaglomerular cells
renin
NaCl
ANGII is a vaso______ that increases ___ reabsorption in the ____ tubule, in addition to stimulating ___ & ____ secretion from the ____.
vasoconstrictor
Na+
Proximal
Thirst
Aldosterone
Adrenal cortex
Aldosterone increases ___ reabsorption and ____ secretion by ____ cells in the ____ tubule & _____. Aldosterone is secreted in response to ____, ____, or ____.
Na+
K+
principle cells
Distal tubule & collecting duct
ANGII, Hyperkalemia, or Hyponatremia
Nerves decrease Na+ excretion in 3 ways
-decrease GFR & RBF>decreased filtered Na+ load for excretion
-Stimulate Na+ reabsorption by renal tubules
-Release Renin>ANGII>Aldosterone> Increased reabsorption
ANP (atrial natriuretic peptide) is secreted by the ___ in response to an ____ in ECF volume. ANP _____ GFR by ____ the afferent & ____ the efferent arterioles. ANP also ____ reabsorptive mechanisms along the tubules & ____ Na+ & H2O excretion.
Atria
Increase
Increases
dilating Afferent
Constricting Efferent
Inhibits
Increases
What reabsorptive mechanisms does ANP inhibit?
-Inhibits Na+ reabsorption at collecting
duct
-Inhibits Renin secretion by juxtaglomerular cells in kidney
-inhibits RAA system
-Inhibits aldosterone secretion by adrenal
gland
-Inhibits ADH secretion
-Inhibits adenylate cyclase in target
tissues
An decrease in which of the following occurs with a decreased intake of Na+ ?
1. Sympathetic activity
2. Renin-angiotensin-aldosterone
3. Na+ reabsorption
4. Antidiuretic hormone
5. Atrial naturietic peptide
ANP
Water is lost ___ through the skin & lungs, and through the ____ & ____.
insensibly
urine
feces
H2O balance is controlled by ________
concentrating or diluting the urine
Filtrate entering the descending limb of the loop of henle becomes progressively more ___ as it loses water (increases ____ in the loop). Water leaving the loop of henle is absorbed by the ____. At the bottom of the loop, tubular fluid is ______. The ascending limb of the loop of henle pumps out __, ___, & ___, and filtrate becomes hypoosmotic. The ascending tubule fluid is _____.
concentrated
osmolarity
highly concentrated
vasa recta
Na+
K+
Cl-
dilute
There are NO _____ channels in the ASCENDING limb of the loop of henle.
Water
Some ____ is absorbed by the vasa recta, however most is trapped in the ____ which contributes to the _____ gradient of the medulla.
NaCl
interstitium (between the loop of Henle tubules & vasa recta)
osmotic
If plasma osmolarity (solute conc) of blood is High, more water is needed in the blood, so ____ will be released to increase H2O reabsorption, leading to ___ urine production.
ADH
less
If plasma osmolarity is low, ADH is NOT released, less water is reabsorbed, and urine is _____.
More dilute
ADH/Vasopressin is secreted by the ____ and allows the formation of ____ in the ___ tubule & collecting duct
posterior pituitary
water channels
late distal tubule & collecting duct
ADH/vasopressin secretion is stimulated by
-plasma osmolarity rises 1mOsm/L
-Hypovolemia >8%
ADH functions to
-reabsorb H2O
-Increase urine osmolarity
-decrease urine flow volume
ADH is a ____ hormone that attaches to the ADH receptor, which is a ____ receptor that increases _____ in ____ cells, causing the insertion of _____ in the principle cells, facilitating active H2O reabsorption in the _____ tubule & _____.
peptide
GPCR
cAMP
Principle cells
aquaporin water channels
late distal tubule & collecting duct.
What actions does ANGII have that are not related to its ability to vasoconstrict?
Increases Na+ reabsorption by the proximal tubule
ANP actions
High blood pressure stretches the heart
chambers, stimulating release of atrial natriuretic hormone by the right atrium.
This decreases aldosterone secretion. It will decrease reabsorption of Na +
and water from the urine, lowering blood volume.
A buffer is any substance that can _________. It can be a mixture of weak acid & its _____ OR a weak base & its ____.
reversibly bind H+
Conjugate base
conjugate acid
Extracellular Buffers
Intracellular Buffers
EC Buffers:
blood proteins
Inorganic phosphates
IN Buffers:
Hemoglobbin
ATP
ADP
G6P
Buffering systems work (time)
Body fluid buffering systems= Immediately
Respiratory response= minutes
Renal response= hours-days
____% of HCO3- is reabsorbed in the ____ tubule
80-90%
proximal tubule
H+ can be excreted as ___ in the ___ tubule & ____, and as a result 1 new ___ will be formed.
NH4+
proximal tubule & collecting duct
HCO3-
- If the acid-base disturbance is metabolic (HCO3-) the primary compensation response is respiratory to alter PCO2 (some renal days later)
- If the acid-base disturbance is respiratory (PCO2) then compensation response is ONLY metabolic (renal) to
alter [HCO3-] 1
True
