Respiratory Flashcards
What is the function of turbinates?
To humidify and warm air to body temperature
What are the directions of the muscle fibers in the external and internal intercostal muscles?
External intercostals - “hands in front pocket”
Internal intercostals - “hands in back pocket”
The amount of air brought in during normal breathing
Tidal volume
The amount of air brought in during a maximal inhalation
Maximal inspiratory effort
The difference between the tidal volume and maximal inspiratory effort
Inspiratory reserve volume
The amount of air breathed out during a maximal exhalation
Maximal expiratory effort
The difference between the tidal volume and the maximal expiratory effort
Expiratory reserve volume
Maximal breath in and maximal breath out as hard and as fast as a person can in 1 sec
Forced expiratory volume
FEV1
MIE + TV + MEE
Vital capacity
Maximal breath in and maximal breath out as hard and as fast as a person can
Forced vital capacity
The volume of air that is in the lung when the person is relaxed (no inspirations or expirations)
Functional residual capacity
How much air is left in the lung after you have maximally expired
Residual volume
RV + VC
OR
RV + ERV + TV + IRV
Total lung capacity
What are the features of the conducting zone of the lungs?
- Contains the first 16 generations of bronchial branches
- no alveoli
- anatomical dead space
What are the features of the transitional zone of the lungs?
- Contains generations 17-19 of bronchial branches
- some alveoli
What are the features of the respiratory zone of the lungs?
- Contains generations 20+ of bronchial branches
- many alveoli
- major site of gas exchange
Why isn’t the cartilage of the trachea complete?
To allow swallowing in the esophagus
Why do bronchi have irregular cartilage plates in addition to a muscle layer and elastic fibers
To allow for constriction/dilation
Why do bronchioles have a tendency to collapse?
- No cartilage
- progressively thinner muscle layer
Alveolar septa are interconnected via collagen/elastin fibers to provide what? How is this beneficial?
Lateral traction
Keeps the alveoli open —> one alveolus can’t change shape without affecting its neighbors
What are the two main secretory cells in the airway tract? What do they secrete and what does it do?
Goblet cells - mucus; traps harmful substances
Clara cells - CCSP (clara cell secretory protein); anti-inflammatory/immunomodulatory
Which cells proliferate in the alveolar-capillary units during injury and why?
Type II cells to maintain epithelial surface integrity
Immune cell present in the lung to phagocytize foreign particles
Alveolar macrophages
What part of the CNS controls “autonomic” breathing?
Medullary Respiratory Center (Medulla)
What are the 5 main functions of the respiratory system?
- Gas exchange
- Acid-base balance
- Phonation
- Pulmonary defense
- Pulmonary metabolism
What is the acid-base balance equation?
CO2 + H2O H2CO3 H+ + HCO3-
What does the CNS have sensors for in order to control breathing?
CO2 and H+
How is sound produced?
CNS control of respiratory muscles causes air to flow through the vocal cords and mouth
What size particles are filtered out in the nasal passages and how?
10-15 um
Nasal hairs + turbulence in air flow
What size particles are filtered out in the small airways via sedimentation (due to gravity)?
2-5 um
What size particles are filtered out via entrapment in the mucus?
> 2 um
Traps and “sweeps” foreign materials up toward the pharynx
Mucociliary escalator
How does a cough/sneeze contribute to pulmonary defense? How are they triggered?
Particles mechanically/chemically trigger cough (in trachea) or sneeze (in nose/pharynx)
Forced expired air produces a high air flow that rubs against walls and forces mucus up through the airway
What role do immature mononuclear phagocytic cells play in the airways?
They engulf bacteria and other antigens that causes them to mature
What role do mature dendritic cells play in the airways?
The migrate to lymphoid tissue where they present the antigen they engulfed and either activate T cells/immune response/inflammation or they promote antigen tolerance/suppress the immune response (depending on the antigen)
Where are dendritic cells located in the immune system?
From trachea to alveoli
What role do alveolar macrophages play in the respiratory system?
- Engulf and destroy antigens with lysosomes
- engulf non-degradable particles and migrate to mucociliary escalator for removal
- role in immune/inflammatory response
How does cigarette smoke damage the airways?
- damages cilia in mucociliary escalator
- inhibit activity of alveolar macrophages
What role do surface enzymes and mucus play in pulmonary defense?
Contain antibacterial components that inactivate bacterial enzymes and factors
What major role does the pulmonary system play in circulation besides oxygenating blood?
It traps substances/clots in pulmonary capillaries and the immune system removes them
Cells that cause bronchoconstriction, immune responses, and cardiopulmonary reflexes
Mast Cells
What substances do mast cells release?
Histamine Lysosomal Enzymes Prostaglandins Leukotrienes Platelet activating factors Neutrophil and eosinophils chemotactic factors Serotonin
What immunologically active substances produced by the lung tissue can end up in the blood?
Bradykinin Histamine Serotonin Heparin PGE2 and PGF2alpha
Substance produced by Type II alveolar cells that reduces surface tension in alveoli
Surfactant
Tidal volume * frequency of breaths
Minute ventilation
Makes lungs tend to empty/collapse or expand
Lung elastic recoil
Makes the rib cage tend to expand or collapse
Thoracic cage elastic recoil
Equal to Paw (pressure of air way) at rest OR the combined compliance of zero
functional residual capacity
What two forces contribute to the negative intrapleural pressure?
Lung elastic recoil
Thoracic cage elastic recoil
Before inspiration, what forces are acting on the respiratory system and what is Paw and Pip?
Lung elastic recoil = Thoracic cage elastic recoil
Pip = lung elastic recoil
Paw = 0
No air flow.
During inspiration, inspiratory muscles are active. What forces are acting on the respiratory system and what is Paw and Pip?
Lung elastic recoil <
Thoracic cage elastic recoil + muscle forces
Pip = more negative
Paw = negative
Air flows in.
At the end of inspiration, inspiratory muscles are actively holding lung at increase volume. What forces are acting on the respiratory system and what is Paw and Pip?
Lung elastic recoil = thoracic cage elastic recoil + muscle forces
Pip = negative = lung elastic recoil
Paw = 0
No air flow.
During expiration, inspiratory muscles are inactive. What forces are acting on the respiratory system and what is Paw and Pip?
Lung elastic recoil > thoracic cage elastic recoil
Pip = less negative = lung elastic recoil
Paw = increases
Air flows out.
What is the equation for transpulmonary pressure and what does it represent?
Changes in alveolar distending pressure
Transpulmonary pressure = Palv - Pip
Why does increased transpulmonary pressure lead to increased lung volume?
It is the pressure difference between the alveoli and the intrapleural space. If it that pressure difference increases, it means the lungs will be pulled open and lung volume will increase
What is the equation for the chest wall’s distending pressure?
Distending pressure = Pip-Patm
What is the equation for compliance?
C = change in volume/change in pressure
What will high compliance show vs low compliance?
High compliance = small pressure change with large volume change
Low compliance = large pressure change with small volume change
Ease of stretch or distensibility
Compliance
Tendency to oppose stretch or dissension; ability to return to original after stretching
Elasticity
What is hysteresis?
A difference in the PV curve where inflation is at a lower totally lung volume that expiration - due to surfactant
What is the equation for lung compliance?
Change in lung volume / transpulmonary pressure
What is the equation for chest wall compliance?
Change in lung volume / chest wall’s distending pressure
What is the equation for combined (lung + chest wall) compliance?
Change in lung volume / (alveolar pressure - atmospheric pressure )
What can cause changes in chest wall compliance?
Pregnancy or obesity - Decrease range of motion of diaphragm
Musculoskeletal disorders - decrease motion of rib cage
What is the Law of LaPlace?
P = 2T/r
Where:
T = wall tension
R = radius
What happens to the intrapleural pressure if lung elasticity decreases (due to aging or disease)?
It becomes less negative
Why do smaller alveoli have higher pressure?
Because surface tension is the same for all alveoli so the driving force for pressure is dependent on radius (smaller radius = higher pressure)
How does surfactant work to keeps the lungs from collapsing?
- decreases surface tension
- increases lung compliance
- breaks up water molecules and is more effective in smaller alveoli
What is surfactant made out of?
85-90% lipids and 10-15% proteins
What contributes to pulmonary resistance?
Lung Tissue resistance (20%) Airway resistance (80%)
Where is the largest resistance in the lungs?
In the LARGER segmental bronchi (no cartilage, less surface area)
What is Poiseuille’s Law?
R is proportional to (n*L)/r^4
F = deltaP/R
F is proportional to (deltaP * r^4)/(n*L)
F = flow R = resistance DeltaP = pressure difference r = radius n = viscosity L = length
What happens to resistance during inspiration and expiration?
As lung expands, radius of alveoli increases and resistance decreases
Small changes in radius = big changes in resistance (r^4)
What factors affect resistance in the airway?
Transpulmonary pressure (indirectly related) Lateral traction/elastic recoil (directly)
What determines the radius of alveoli?
Transpulmonary pressure gradient
Describe dynamic airway compression.
As air moves out, it rubs against the walls of the airway ad pressure drops on the way out.
At the equal pressure point (EPP), the pressure equalizes with the intrapleural pressure and the. Airway can collapse (if not reinforced by cartilage)
Why is dynamic airway compression more likely to happen at low lung volumes than high lung volumes?
It happens in low lung volumes because the alveolar pressure is lower and closer to the intrapleural pressure and so the EPP shifts down and if it ends up in non-cartilaginous bronchi the airway will collapse
At what point of VC is dynamic airway compression?
High risk of airway compression in low lung volumes (<60%)
Why do we see “pursed-lip” breathing in patients with lung diseases of increased compliance?
“Pursed lips” will increase airway resistance and thus airway pressure, moving the EPP higher and reducing the risk of airway collapse
Volume at which airway closure begins during forced expiration
Closing capacity
The volume expired from closing capacity to residual volume
Closing volume
How does emphysema affect closing capacity?
Decreased in elastic recoil —> decrease in lateral traction to help get air out —> increased closing capacity
Airways close at higher volumes + trap gas
Patient breaths at higher volumes to increase recoil
What is Henry’s Law and what does it measure?
C = P * S
C = concentration P = partial pressure S = solubility
What is Fick’s Law and what does it measure?
V = DSA(P1-P2)/deltaX
D = diffusion coefficient S = solubility A = surface area of barrier P1-P2 = partial pressure gradient DeltaX = thickness of barrier
Volume of gas diffusing through alveolar-capillary barrier per unit of time
The diffusion coefficient is indirectly proportional to what?
The molecular weight (aka. The bigger the molecule, the slower it diffuses)
Why does CO2 diffuse faster than O2 despite having a lower diffusion coefficient?
It’s is 24x more soluble due to the bicarbonate system
What is Dalton’s law and what does it measure?
Pgas = Ptotal * Fgas
Determines partial pressure of a gas
IN LUNGS:
Pgas = (Ptotal - PH2O) * Fgas
How much pressure does water vapor exert always?
47 mm Hg
How does the rate of diffusion change along the length of the capillary at the alveolus?
It decreases
The changes in blood partial pressures for oxygen and CO2 are +60mmHg and -6mmHg respectively but the amounts of gas moved are roughly the same… how is this possible?
CO2 has a high solubility so a small pressure difference can move a large amount of gas where as oxygen is less soluble
Why is there still a lot of CO2 left in the blood after gas exchange?
Due to bicarbonate which plays a role in blood pH
When and won’t you see equilibrium in gas exchange?
Perfusion-limited = equilibrium Diffusion-limited = no equilibrium
What is the equation for the diffusing capacity of the lung?
DL = DSA/deltaX
What gas is diffusion capacity measured with and why?
Carbon monoxide because it binds immediately with hemoglobin and doesn’t accumulate in the blood (partial pressure is 0); diffusion limited
What is PAO2 determined by?
Balance between removal of O2 and replenishment by ventilation
What is PACO2 determined by?
Balance between addition of CO2 and removal by ventilation
What is the alveolar ventilation equation?
VA = VCO2*(Pb - 47mmHg)/PACO2)
VA = volume of alveolar gas VCO2 = volume of CO2 produced Pb = barometric pressure PACO2 = pressure of alveolar CO2
What is the alveolar gas equation?
PAO2 = PIO2 - (PACO2/R)
PAO2 = pressure of alveolar O2 PIO2 = pressure of inspired oxygen PACO2 = pressure of alveolar CO2 R = respiratory exchange quotient
What is minute ventilation (VE)?
VE = (VDf) + (VAf)
What is the equation for tidal volume?
VT = VD + VA
VD = volume of an atomic dead space VA = volume of alveoli
How much time does blood spend in the pulmonary capillaries? How long does it normally take for O2 to reach equilibrium?
- 75 sec
0. 3 sec
Alveoli that can not be perfused
Alveolar dead space
What is physiologic dead space?
Alveolar dead space + anatomical dead space
How is physiologic dead space measured? What is the equation?
Simplified Bohr Equation:
VD/VT = (PACO2 - PECO2)/PACO2
VD = volume of physiologic dead space VT = tidal volume PACO2 = pressure of alveolar CO2 PECO2 = pressure of expiratory CO2
Low oxygen delivery to tissues
Hypoxia
Low oxygen content in blood
Hypoxemia
What are the causes of hypoxemia?
Hypoventilation
Diffusion impairment
Shunt
V-Q mismatching
Describe compliance at the apex vs. the base of the lung.
Due to gravity, the intrapleural pressure is higher at the top of the lung (alveoli are more distended) so compliance is lower
Describe perfusion at the apex vs. the base of the lung.
Due to gravity, there is a drop in hydrostatic pressure at every level above the heart —> decrease BP —> less distended vessels —> reduced radius —> increased resistance —> decreased blood flow
Why is a normal V/Q 0.8 and not 1.0?
Perfusion usually has a steeper gradient and makes more of a difference (due to gravity)
Capillaries that have no gas exchange in the lungs; function is to dilate as lung expands to reduce resistance
Extraalveolar capillaries
Capillaries in the lung that constrict during inhalation leading to more resistance
Alveolar capillaries
What leads to decreased vascular resistance during inhalation?
Extraalveolar capillaries
Lateral traction
Poorly ventilated lung units that equilibrate to near mixed venous blood
Shunt
Poorly perfused lung units that equilibrate to near inspired air
Dead space
What is V/Q at the apex of the lung compared to the base?
Apex - high V/Q
Base - low V/Q
How do the different V/Q regions of the lung affect arterial blood?
The blood at the base is “wasted perfusion because it is better perfused than ventilated. The blood at the apex is “wasted ventilation” because it is better ventilated than perfused.
How do the oxygen partial pressures compare at the apex of the lung?
PA>Pa>Pv
How do the oxygen partial pressures compare at the base of the lung?
Pa>Pv>PA
What are some examples of hypoxia?
Anemia
Blood loss
Decreased cardiac output
What are some examples of hypoxemia that would cause a normal A-a gradient? Is it responsive to O2?
Hypoventilation
Altitude
Responsive to O2.
What are some examples of hypoxemia that would cause a increased A-a gradient? Is it responsive to O2?
Shunt/V-Q mismatch
diffusion problem
R—>L shunt
Not responsive to O2.
What is a normal A-a gradient?
4-10 mmHg
When would we see perfusion-limited oxygenation?
Exercise (normal)
When would we see diffusion/ventilation-limited oxygenation?
In a pathological condition (ie. shunt, V/Q mismatch, etc.)
How is diffusion tested?
DCLO - tests diffusion with CO because it binds immediately with Hb
What is the cause of NATURAL shunts?
Mismatching of ventilation and blood flow in various parts of the lungs
What is the normal V/Q ratio and what does it mean?
0.8
Normal VA = 4 L/min
Normal pulmonary blood flow = 5 L/min
What are examples of normal R—>L shunts?
- returning bronchial circulation to left heart via pulmonary veins
- Returning coronary venous blood to the left ventricle via thebesian veins
What can cause a physiologic R—>L shunt?
Congenital heart disease (atrial septal defects, patent foramen ovale)
Pulmonary disease (cor pulmonale)
abnormal enlargement of the right side of the heart as a result of disease of the lungs or the pulmonary blood vessels
Cor pulmonale
Why wouldn’t supplemental O2 be useful for shunts?
Hb carries most of the oxygen in blood and they are already usually fully saturated. Only a small amount is dissolved as well. Blood is shunted so it never sees the extra oxygen anyway.
What are some examples of diffusion impairment?
- Diffuse interstitial fibrosis
- Asbestosis
- Fluid build up/thickening of alveolar walls (pneumonia)
Why do athletes sometimes have widened A-a gradients?
Huge cardiac output —> short transit time of blood —> blood not fully oxygenated —> decreased PcO2 and widened A-a gradient
How to allosteric properties contribute to Hb binding of O2?
They make each consecutive oxygen easier to bind and vice versa
What happens when you increased PAO2 to 600mmHg?
Increase in total oxygen but minimal — most of the gain is in dissolved oxygen because Hb already fully saturated
What are the Bunsen solubility coefficients for O2, CO2, and N2?
O2: 0.003 mL/100ml/mmHg
CO2: 0.075 mL/100mL/mmHg
N2: 0.0017 mL/100mL/mmHg
How does temperature affect the Hb sat curve?
Increased temp shifts it to the right —> decreases affinity (favors unloading of oxygen)
How does pH affect the Hb sat curve? Why does this occur?
Decrease in pH (increase in H+ ions) shifts it to the right —> decreased affinity
higher hydrogen ion concentration causes an alteration in amino acid residues that stabilises deoxyhaemoglobin in a state (the T state) that has a lower affinity for oxygen
How does PCO2 affect the Hb sat curve? Why does this occur?
Increased pCO2 shifts it to the right —> decreases affinity (favors unloading of oxygen)
Increased CO2 —> signals hypoxia —> decreased affinity for O2
How does 2,3-DPG affect the Hb sat curve? Why does this occur?
Increased 2,3-DPG shifts it to the right —> decreases affinity (favors unloading of oxygen)
Chronic hypoxia, anemia, acclimation to altitude —> low RBC PO2 —> increased glycolysis and 2,3-DPG —> lowers hemoglobin’s affinity for oxygen by binding preferentially to deoxyhemoglobin
*Glycolysis is part of both anaerobic and aerobic pathway but produces 2 ATP so it is essential for keeping energy up
How does myoglobin differ from hemoglobin?
- found in tissues
- high affinity for O2
- last ditch oxygen reserve in cells (mostly muscle)
- regular curve vs. sigmoidal
How does anemia change the hemoglobin sat curve?
Maintains sigmoidal curve but its lowered because anemic blood can’t carry as much oxygen
How does CO poisoning change the Hb sat curve?
Shifts to a regular curve (comparable to myoglobin curve); CO binds to Hb 200x better that O2 —> Hb carries less oxygen and reduces O2 delivery to tissues
How is CO poisoning treated?
- High flow O2
- Hyperbaric oxygen chamber (increased pressure decreases binding of CO-Hb)
What is the chemical equation for CO2 transport in blood?
CO2 + H2O —> H2CO3 —> H+ + HCO3-
What happens to CO2 transport in tissues?
increased CO2 —> increase H+ + HCO3-
HCO3 is pumped out using an HCO3-/Cl- transporter
H+ binds with histidines on hemoglobin and decreased affinity for oxygen
What happens to CO2 transport in the lungs?
Decreased PCO2 —> decreased H+ and HCO3-
HCO3- is pumped back into the RBC to make CO2
H+ un-binds from RBC, increasing affinity for O2
Which enzyme is responsible for converting CO2 to H2CO3 and vice versa?
Carbonic anhydrase
What role to carbamino compounds in RBCs play in increased PCO2 (tissues)?
CO2 bind with Hb-NH2 to form Hb-NH-COO- and H+
H+ binds to histidine on Hb and decreases affinity for oxygen
What are the ratios of transported forms of CO2?
Carbonate - 60%
Carbamino - 30%
Dissolved - 10%
The more CO2 bound to hemoglobin the less affinity for oxygen and vice versa
Haldane Effect
Why is deoxygenated blood able to carry more CO2 that oxygenated blood?
Carbamino
The increase in frequency of impulses from respiratory muscle nerves at the onset of inspiration and rapid decrease near the end of inspiration
Augmenting
What 3 things increase the depth of respiration?
- increased impulses from each motor unit
- recruitment of motor units
- longer duration of burst of impulses
How are TV and RR related?
Inversely proportional
Respiratory center in the Nucleus of the Solitary Tract in the medulla associated with inspiration only
Dorsal Respiratory Group (DRG)
Respiratory center in the medulla associated with inspiration AND expiration
Ventral respiratory group (VRG)
Respiratory center in the upper pons associated with early cut off of respiration
Pneumotaxic center (pontine respiratory group)
What results in apneustic breathing?
Lesion of BOTH the pneumotaxic respiratory group and the vagus nerve
What part of the respiratory center is responsible for the self-cycling circuits of respiration?
DRG
What part of the respiratory center is responsible for the pacemaker activity of respiration?
Pre-Botzinger complex in the ROS trail portion of the VRG
Describe the process of the self-cycling circuit in respiration.
DRG/VRG activate —> B medullary neurons (DRG also activates motor neurons in cervical spinal cord and external intercostals) —> C inhibitory neurons —< DRG
How does the pontine respiratory group affect the self-cycling respiratory circuit?
It activates the C neurons which inhibit DRG (end inspiration)
How does the vagus nerve affect the self-cycling respiratory circuit?
It’s activates the medullary B neurons, which activated C neurons, which inhibit DRG
Pulmonary stretch receptors in the airway smooth muscle layer detect lung inflation and stimulate vagus nerve activity (inhibit inspiration)
Hering-Breuer reflex
Where are the peripheral chemoreceptors located?
Carotid (carotid sinus) and aortic bodies
Where are the central chemoreceptors located?
Ventral surface of the medulla
Changes in oxygen and pH stimulate which receptors? What about CO2?
O2/pH - peripheral
CO2/CSF pH - central
What difference in PCO2 will double ventilation?
3 mmHg
What is the maximum PCO2 that the central chemoreceptors will respond to? Why?
70-80 mmHg
Toxic effects of high CO2 on central neuronal function will decrease ventilation
What happens with chronically elevated PCO2 levels?
Chronically decreased pH of CSF —> compensatory increase in HCO3- (shifts equilibrium left)
Also decreased sensitivity of central chemoreceptors
What happens with chronically reduced PCO2 levels (high altitude)?
Chronically increased pH of CSF —> compensatory decrease in HCO3- (shifts equilibrium right)
Also increased sensitivity of central chemoreceptors
What is the most important peripheral chemoreceptor?
Carotid bodies
At what change in fractional atmospheric O2 will we see an increase in ventilation?
A fraction of less than 10%
Blood: ~60 mmHg
Which cells in the peripheral chemoreceptors respond to O2 levels? How so?
Type 1 Glomus cells —> O2 sensitive channels sense decreased PO2/blood flow/pH —> K+ channels close —> depolarization
What happens if you lesion the peripheral chemoreceptors?
Complete loss of respiratory response to changes in arterial PO2 (PCO2 response intact)
How do central chemoreceptors respond to pH? How do H+ ions cross the BBB?
They respond to LARGE changes in pH; however, pH only has a small effect
“breaks” in the BBB allow H+ to cross
What are the other inputs to the respiratory centers aside from the peripheral and central chemoreceptors (6)?
- cerebral cortex: voluntary control
- hypothalamic center/limbic system: emotional states
- hypothalamic/skin temperature receptors: helps lose body heat
- muscular/join receptors: exercise
- medullary reflexive areas: swallowing/vomiting
- baroreceptors: increase RR with decreased BP and vice versa
At what age is the Hering-Breuer inflation reflex strongest?
In un-anesthetized infants during the first 5 days of life
Where are irritant receptors in the airway located and what do they respond to?
Between epithelial cells
Noxious gases, ammonia, cigarette smoke, histamine
Where are J (juxtacapillary) receptors in the airway located and what do they respond to? What nerve to they travel in?
Conducting airways and alveoli
Chemical and mechanical stimulation
Vagus nerve (slowly conducting, unmyelinated, C fibers)
What is Cheynes-Stokes breathing and what causes it?
Hyperventilation followed by deep respiration excursions that diminish to the point of apnea
Caused by abnormally long delay for transport of arterial gases from pulmonary circulation to the brain
What is apneustic breathing and what causes it?
Deep inspirations lasting from 30-90 seconds followed by brief periods of expiratio
Cause by damage to pons or medulla
What is sleep apnea and how is it treated?
Mechanical blockage of airways prevents inspiration —> rise of PACO2 a d fall of PO2 levels leads to arousal and opening of airway
Treated with nasal CPAP
What is the equilibrium equation for blood pH?
PH = pKD + log [AC-]/[HAc]
When optimal buffering occurs, what is true about pH?
Optimal buffering: pH = pKD
[Ac-]/[HAc] = 1
What are the 3 main buffering systems in the body?
Phosphate buffer system
Proteins (hemoglobin)
Carbonate buffer system
What is the equation and pKD of the phosphate buffer system?
NaHPO4-2 + H+ —> NaH2PO4-
pKD = 6.8
What is the pKD for the hemoglobin buffer system? Which amino acid is the main contributor to this buffer?
Histadine
The pKD = 7.0-7.8
What organs regulate the carbonate system?
Kidneys and lungs
A pH of 7.4 in the blood is equal to which concentration of protons?
40 nMol
If acid is added to the blood, how does it affect the pH and buffer concentrations?
Most of it binds with buffers but some remains dissolved = deacreased pH
The ratios for ALL buffers are still independently in equilibrium with the new pH
What is the normal bicarbonate concentration for a blood pH of 7.4?
24 mMol
What happens during metabolic acidosis? What are the compensatory mechanisms?
Increased H+/removal of HCO3- (diarrhea) —> shift eq right —> decrease pH —> detection by peripheral chemoreceptors —> increase ventilation —> lowers PCO2 —> drives reaction back to left
**brain senses low CO2 levels but not pH —> opposes hyperventilation (doesn’t completely compensate)
When all buffers in a solution are in equilibrium with the same H+ concentration
Isohydric principle
What happens during metabolic alkalosis? What are the compensatory mechanisms?
Addition of HCO3-/removal of H+(vomiting) —> shift eq left —> increase pH —> detection by peripheral chemoreceptors —> decrease ventilation —> raises PCO2 —> drives reaction back to right
**brain senses higher CO2 levels but not pH —> opposes hypoventilation (doesn’t completely compensate)
What happens during respiratory acidosis? What are the compensatory mechanisms?
Decreased ventilation —> increased CO2 —> shifts eq right —> increased H+ —> increased formation of bicarbonate in kidneys to shift eq back left
What happens during respiratory alkalosis? What are the compensatory mechanisms?
Increased ventilation —> decreased CO2 —> shifts eq left —> decreased H+ —> decreased formation of bicarbonate in kidneys to shift eq back right
The proportion of whole blood that is composed of red blood cells
Hematocrit (normal: 45-50%)
When blood is centrifuges, this layer is the one that contains leukocytes and platelets
Buffy coat
How much Hb is is RBCs? Why does it need to be in RBCs?
30 g/dL
Hb has a short half-life in circulation and packaging in RBCs shields it from rapid removal
What are some unique characteristics of RBCs?
- Has no nucleus, ribosomes, ER, or mitochondria
- No protein synthesis once mature
- 120 day lifespan
Formed in slow flowing blood when RBCs stack up/stick together
Rouleaux
Why is the biconcave shape beneficial for a RBC?
Needs to deform to pass through capillaries —> more flexible
What protein is responsible for the shape of RBCs?
Spectrin
What does a deficiency of spectrin result in?
Spherocytosis - sphere-shaped RBCs with much shorter half-lives
What happens if RBC gets depleted of ATP?
RBC becomes crenated (shrivels up). ATP important in maintaining cell shape
How is ATP made in RBCs?
Anaerobic glycolysis
How does the RBC get glucose?
It readily diffuses into the cell (not insulin required)
Where does most of the RBCs energy go?
ATPase pumps
Also some to Ca+2 pumps to pump calcium out
What happens if Ca+2 accumulates in the RBC?
RBCs form “spikes” and becomes an echinocyte
What occurs with sickle cell anemia?
Change in a single Hb amino acid —> low O2/pH causes HbS to crystallize and aggregate to form long rigid rods —> leads to “sickle” shape
Why are sickle cells problematic?
- not flexible
- blocks vasculature (which deceases O2 even more and propagates the problem)
What happens in a sickle cell crisis?
Build up of sickle cells becomes irreversible, non-functional, and leads to breakdown and removal of RBCs
Why is oxidation harmful to RBCs?
- damages Hb
- Fe2+ can be oxidized to ferric iron Fe3+ (methemoglobin) which is non-functional
Enzyme in the RBCs that restores iron to Fe+2 form using NADH as a cofactor
Methemoglobin reductase
How does H2O2 damage hemoglobin? What is the defense mechanism against this?
H2O2 cross-links cysteine of Hb and inactivated it
Presence of GSH - reacts with H2O2 to protect Hb
How does GSH (glutathione) get reduced back to normal?
Glutathione reductase uses NADPH to reduce glutathione
Where does NADPH in RBCs come from?
Glucose-6-phosphate dehydrogenase
What would happen if a patient had a deficiency in G6PD?
Hemolytic anemia
Why is 2,3-DPG important in RBCs?
In low levels of O2, 2,3-DPG binds to Hb and reduces the affinity for O2 to increase tissue delivery
Where are RBCs made in the fetus? What about at birth? As an adult?
Fetus: yolk sac/liver/spleen
Birth: bone marrow only
Adult: axial skeleton
How does bone marrow make RBCs?
Marrow precursors (stem cells) —> 4 divisions —> normoblasts —> Hb synthesis for 4-5 days —> Hb reaches mature levels —> nucleus/mitochondria extruded —> reticulocyte —> enters circulation and Hb synthesis continues for about 2 days before RNA/ribosomes/ER break down —> mature RBC
How is the formation of RBCs regulated?
Low O2 detected by JG apparatus in the kidney —> kidney releases erythropoietin (EPO) —> EPO stimulates formation and maturation of RBC precursors
% of RBCs that are reticulocytes
Reticulocyte index
What would cause the reticulocyte index to increase?
Increased production of RBCs (indicative of anemia)
What is required for Hb formation? Where does Hb production occur?
Occurs in normoblast
Iron-dependent: recycled from old RBCs, body stores, and GI tract
How is Hb formed?
Transferrin binds recycled iron —> uptake of transferrin by normoblast —> iron released into cell —> iron moves into mitochondria and made into heme while alpha and beta chains are made by the ribosomes
How is iron stored in the normoblast until it is ready to be used?
Stored in hemosiderin
What happens when RBCs are near their end of life?
Become senescent —> lose flexibility and denatured Hb forms lumps) —> recognized by macrophages and engulfed, mainly in spleen
How does the spleen aid in filtering out old RBCs?
Old RBCs are less flexible and get stuck in crevices of spleen
Breakdown or lysis of RBCs in macrophages
Extravascular hemolysis
What happens during extravascular hemolysis?
RBC broken down into heme chain (recycled via transferrin), goblin (broken down into amino acids), and porphyrin ring (broken down to bilirubin, which is bound to albumin, taken to liver, and excreted in feces)
What happens during intramuscular hemolysis?
Hemoglobin released into blood:
- Hb becomes oxidized to methemoglobin - globin becomes amino acids and heme group bound by hemopexin and brought to liver where its broken down
- Hb split into dimer —> binds with haptoglobin —> brought to liver to be broken down (if no haptoglobin available, dimers are excreted in urine by kidneys)
What are some signs of intravascular hemolysis?
- low levels of haptoglobin (seen after 5 days)
- hemoglobinuria - hemoglobin in urine (last for 2 days)
What are some causes for hypoproliferative anemia?
- iron deficiency
- acute bleeding (losing recyclable iron)
- inflammation (macrophage hangs onto iron, iron feeds bacteria)
- bone marrow damage
- inability to release EPO (signaling molecule for erythropoiesis
What are some examples of hemolytic anemias?
- G6PD deficiency - increases RBC sensitivity to oxidative agents
- Sickle cell - RBCs deformed + trapped in spleen
- Hereditary spherocytosis - RBCs suffer damage when passing through spleen
Anemia caused by vitamin B12 deficiency
Pernicious anemia
When alpha and beta globin chains are not synthesized in equal amounts —> destruction of RBC precursors in marrow
Thalassemia
Describe what happens in a mother who is Rh-negative with an Rh-positive fetus.
Red cells from baby introduce D antigen to maternal circulation at birth —> mother forms antibodies —> second Rh+ fetus —> Rh antibodies attack fetal RBCs
Hemolytic disorder of the fetus due to Rh antibodies; effects may be irreversible (high bilirubin can cause fetal brain damage)
Erythroblastosis fetalis
How is Erythroblastosis fetalis treated/prevented?
Treated:
- fetal transfusion
- plasma exchange for mother (to dilute antibodies)
Prevented:
-Rhogam (antibodies to D antigen that rapidly remove it from maternal circulation at birth)
