lecture 33+34+DLA Flashcards
area of the brain responsible for breathing rhythm
pre-botzinger area in the rostral ventromedial medulla
neurons that drive inspiration?
DRG (doral root ganglion) and rostral VRG (ventral respiratory group)
pontine nuclei
switch between inspiration and expiration
pons
The reflex pathways?
- pulmonary stretch receptors: respond to transmural pressure
- irritant receptors: in response to touch or certain substances; results in coughing/ gasping
- proprioceptors: signal breathing effort
- J receptors: fire in response to lung injury, results in shallow breathing, airway secretion, constriction
central receptors?
located in the medulla
responds to changes in pH and CO2 levels of CSF
H+ and HCO3 permeability (BBB)
largely impermeable
CSF sensitivity and breathing rate
sensitive to changes in CO2
affected by respiratory acid/base changes
CSF pH decreases (coming more acidic) the rate
of ventilation increases blowing away the acid (CO2)
peripheral chemoreceptors
located in carotid and aortic body
detect changes in pH, O2, and CO2
carotid: glosso-pharyngeal nerve (afferent to CNS)
aortic: vagus nerve (afferent to CNS)
treatment for patient with breathlessness?
administration of oxygen
do not give 100 percent oxygen, titrate it
maintain O2 (60-65mm) (88 to 92%)
which way does the flow volume loop move during obstructive and restrictive lung diseases?
obstructive: moves to left
restrictive: Moves to right
airway resistance decreases going down the respiratory tree even though radius get smaller, why?
The radius is smaller, but the cross sectional area is very large
thus air way resistance decreases
flows in a parallel fashion
which areas have the largest and smallest airway resistance?
highest: medium-sized bronchi
smallest: small airways
what has the greatest impact on air flow into lungs
The radius!
R = 8nL / pi (r)4
reducing radius by 1/2, increases resistance by 16!
what diseases have a large increase in airway resistance?
COPD and asthma
V = delta P / R
must compensate by breathing harder
dynamic airway compression
starts after the equal-pressure point (EPP)
increases resistance to airflow and limits flow during expiration (flow is limited by collapsed airways)
collapse due to intrapleural pressure becoming greater than the alveolar pressure (forced expiration)
compression decreases radius and increases resistance
alpha and beta globin genes?
where are they on the chromosome and how many copies?
alpha globin is found on chromosome 16 and their are 4 genes.
beta globin is found on chromosome 11 and their are two genes.
expression patterns of the globin genes during fetal life? adult life?
fetal: high gamma, zeta, and alpha expression
low beta expression
adult: high alpha and beta expression
low gamma expression
what are the compositions of HbA, HbF, and HbA2?
HbA: two beta and two alpha (most common)
HbF: two alpha and two gamma (fetal)
HbA2: two alpha and two delta
Hemoglobin S
also known as sickle cell disease
single point mutation in the Beta-globin gene on the 6th codon.
glutamic acid to valine
autosomal recessive inheritance
the presence of ‘sticky’ patches, thus can lead to sickling/polymerizing
Can sickle cell anemia be distinguished during fetal life?
No.
beta-globin protein has low expression until birth
what is the treatment for HbS?
Hydroxyurea (inhibit histone deacetylation)
this drug will increase fetal globin expression
de-repression of the gamma globin gene
More HbF formation
Hemoglobin C
point mutation at the 6th codon of the B-globin gene, thus a missense mutation
glutamic acid to lysine (a + AA)
homozygotes have mild hemolysis
low solubility
HbSC disease
Two different mutations on the beta globin gene
sickling is similar to sickle cell disease but more mild
what does the electrophoresis look like when comparing globin proteins?
HbA moves the furthest
HbF moves second furthest
HbS (sickle cell) moves third furthest
HbC moves little
A, F, S, C (in order)
A Fat Santa Clause
overview of beta and alpha thalassemia?
Alpha - reduced alpha chain synthesis
beta - reduced beta strand synthesis
alpha thalassemia?
what are the four different kinds?
reduced alpha chain synthesis
- normal, all 4 genes are functional
- silent carrier, 3 of the genes are functional (no symptoms)
- cis and trans carrier (heterozygote)
cis: deletion of two genes on the same chromosome
trans: deletion of one copy from each chromosome
may have mild anemia
4. HbH alpha thalassemia deletion of three genes; one functional allele most likely one parent was cis and other was trans presents in infancy or childhood mild to moderate anemia bone changes may be seen aggregation of beta tetramers HbA levels might be low
- hemoglobin bart hydrops fetalis syndrome
most severe form
see Hb bart (aggregations of gamma tetramers)
all alleles are non-functional
no detectable HbF or HbA
lethal occurrence
most likely both parents had a cis mutation
overview of beta-thalassemia
autosomal recessive inheritance
allelic heterogenicity and compound heterogenicity can be seen
variable severity can also be seen
two types of mutations:
- Beta +: reduced expression
- Beta 0: suppression of gene expression
excessive alpha chains can precipitate and lead to severe hemolytic anemia by binding to RBC membranes and causing damage
do not form tetramers
what are the three forms of beta-thalassemia?
major:
two severe mutations
very low levels or absence of HbA
high levels of HbA2 and HbF to compensate
intermedia:
one severe mutation and one less severe or two less severe mutations
Low HbA levels
High HbA2 and HbF levels to compensate
minor:
almost normal levels of HbA
heterozygote
what bone changes are seen in beta- thalassemia?
extramedullary erythropoiesis (looks like hair on the bone)
frontal bossing, malar prominence
Hemophilia A
X-linked recessive
lot enough factor 8 due to gene deletion, intron inversion
replacement therapy is treatment
hemophilia B
X-linked recessive
lost enough factor 9 due to point mutation and deletion
replacement therapy for RX
closed vs open pneumothorax
closed: air goes from lung into pleural cavity
open: air goes from outside the body into the pleural cavity
the lung will collapse due to the transpulmonary pressure becoming zero
what is the tidal volume (TV)?
the volume of air inhaled or exhaled with each
normal breath
what is the Inspiratory Reserve Volume (IRV)?
the volume of air that can be inhaled at the end of a normal tidal inspiration
Expiratory Reserve Volume (ERV)?
the volume of air within the lungs that can be exhaled after the end of a tidal exhalation
Residual Volume (RV)?
the remaining air in the lungs that cannot be expelled
Functional Residual Capacity (FRC)
the total volume of air remaining in the lungs at the end of a tidal exhalation
Total Lung Capacity (TLC)
the volume of air in the lungs at the end of a maximal inspiration
Vital Capacity (VC)
the volume of air exhaled from maximal inspiration to maximal exhalation; maximum expiration
Forced Expiratory Volume in 1 second (FEV1):
the volume of air exhaled in the first second of a FVC test
how to calculate total long capacity
(TLC = IRV+VT+ERV+RV)
how to calculate Inspiratory Capacity
(IC = VT + IRV)
how to calculate functional residual capacity
(FRC = ERV + RV)
how to calculate vital capacity
(VC = IRV + ERV + VT)
what cannot be calculated by spirometry
the residual volume
spirometry and obstructive disorders?
Expiratory flow rate is significantly decreased resulting in decreased FEV1 and FVC
The FEV1/FVC ratio is low
the ratio is lower than 80%
it takes longer to get to the needed volume
spirometry and restrictive disorders?
Lung inflation is decreased resulting in decreased FEV1 and FVC
The FEV1/FVC ratio is normal or increased.
the ratio is still 80%, but the graph looks different.
volume is much lower
FEF25-75
has the greatest sensitivity for the detection of
early airflow obstruction
the flow volume loop and obstructive lung disease?
what about restrictive?
obstructive: will have a ‘scooped out’ appearance
seen commonly in those with emphysema
restrictive: significant reduction in size
what is COPD?
combination of chronic bronchitis, emphysema, and asthma
commonly caused by smoking
decreased airflow, thus reduced FVC, FEV1, and decreased FEV1/FVC ratio
