Respiratory system Flashcards
4 types of catabolic reactions
- production of ATP
- muscle contraction
- reducing equivalents
- biosynthetic precursors
2 types of anabolic reactions
- storage of energy
- production of macromolecules
Gibbs free energy of a reaction
âđş= âđşÂ°+đ đ lnâĄ[đđđđđ˘đđĄđ ]/[đđđđđĄđđđĄđ ]
What R and T under standard conditions?
T - 310.15K
R - 8.314 J K-1 mol-1
How much energy is released on decomposition of ATP?
30.5 KJ mol-1
How much energy is released on decomposition of ADP?
45.6 KJ mol-1
Higher energy compounds can be
used to make ATP
Lower energy compounds can be
activated by ATP
How are the rings of sugars closed?
Addition of H to make alcohol on both ends, hemiacetyl, reversible reaction
What is a six membered ring called?
Pyranose
What is a five membered ring called
furanose
5 important things about glycogen
- the main storage polysaccharide in mammals
- composed entirely of glucose, with 1-4 and 1-6 bonds
How is glucose transported into cells?
- transport is mediated by a number of glucose transporters
GLUT 1&3
mediates basal glucose uptake and found in all cell types
GLUT 2
- Liver - takes up glucose to store as glycogen
- Pancreas - uptake triggers secretion of insulin, increases GLUT 4 in well-fed state
GLUT 4
Found in muscle and adipose tissue
GLUT 5
Transports dietary fructose from small intestine, which can be converted to glucose
What is glycolysis?
- 10 steps in 3 stages
1. activation and rearrangement
2. splitting and phosphorylated C3 sugars
3. conversion of C3 sugars into pyruvate - Takes place in cytosol
What is the yield of glycolysis?
2 x pyruvate
2 x ATP
2 x NADH
Summarise stage one of glycolysis
- 2 x ATP used to activate and form 2 x C3 sugars
- phosphorylation causes ring opening
Summarise stage two of glycolysis
- Aldolase breaks fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate;
- Triose phosphate isomerase catalyses enol/keto tautomerisation.
Summarise stage three of glycolysis
Each step is repeated twice as two molecules
Products for stage 3 are 2 x NADH and 4 x ATP
What is anaerobic respiration?
- Without oxygen, pyruvate is reduced to R/D-lactate
- This oxidises NADH to NAD+ and allows glycolysis to continue;
What is the cori cycle?
- Recycles R-lactate to glucose;
- Lactate goes from muscle to liver, converts R-lactate to pyruvate
- Requires 6 x ATP per glucose molecule - 2 x ATP molecules from glycolysis.
What is gluconeogenesis?
- Occurs mostly in the liver
- 2 x pyruvates for each glucose
- 2 x ATP and 1 x NADH also required
What is the structure of mitochondria?
- Matrix contains the enzymes for the TCA cycle
- Membranes are required for electron transport system
What is the pyruvate dehydrogenase complex?
- Controls entry of pyruvate into the TCA cycle
- Pyruvate dehydrogenase (E1) â decarboxylates pyruvate
- Dihydrolipoyl transferase (E2) â makes CoA
- Dihydrolipoyl dehydrogenase (E3) â converts reduced lipoamide to disulfide
- Mammals have 30 x E1, 12 x E2 and 12 x E3
What is the pyruvate dehydrogenase complex reaction?
- TPP anion adds to pyruvate and CO2 is released
- Lipoamide disulfide is added to acetyl group and redox reaction occurs
What are the phases of the TCA cycle?
- Condensation and rearrangement (1 & 2)
- Decarboxylation (3 & 4)
- Formation of GTP using phosphate anhydride bond (5)
- Conversion of succinate to oxaloacetate (6-8)
What is amphibolic mean?
Used in catabolic and anabolic reactions
What are the products of the TCA cycle?
Acetyl-CoA is oxidised to 2 x CO2
3 x NADH and H+
1 x FADH2
1 x GTP
Summarise stage one of the TCA cycle
Citrate synthase catalyses condensation of acetyl-CoA and oxaloacetate
Hydrolysis of CoA ester makes reaction irreversible
Citrate rearranges to form isocitrate.
Summarise stage two of the TCA cycle
Isocitrate dehydrogenase uses NAD+ to produce a β-ketoacid;
β-ketoacid loses CO2
2-Oxoglutarate is converted to succinyl-CoA by a multi-enzyme complex
Summarise stage three of the TCA cycle
CoA is displaced by inorganic phosphate to produce an mixed acid anhydride
Produces ATP equivalent (GTP);
Phosphate is transferred to an active site His
Transfer of phosphate group onto GDP forms GTP
Summarise stage four of the TCA cycle
Produces reduced cosubstrates
Converts succinate into oxaloacetate in three steps
- Desaturation of C-C bond using FAD;
- Hydration of double bond. Anti-addition of H2O to obtain S-malate;
- NAD+-dependent oxidation to re-form oxaloacetate.
The last step is thermodynamically unfavourable and is driven by conversion of oxaloacetate to citrate, i.e. the availability of acetyl-CoA.
What is oxidative phosphorylation?
Takes place in mitochondria
Requires O2
Two parts
- Generation of a proton gradient;
- Production of ATP
Generates most ATP 26/30
Electrons move faster/slower through
Faster through vacuum
Slower through proteins
What is the chemi-osmotic hypothesis?
ATP synthesis is coupled to the proton gradient
ATP synthesis consists of:
1) proton transport to mitochondrial inter-membrane space
2) transport of protons through inner membrane by ATP synthase
How much ATP is received from degradation of glucose?
30 ATP
5 from glycolysis
5 from pyruvate oxidation
20 from acetyl-CoC oxidation
How are glycogen 1,4 bonds made?
Allows the extension of the glycogen polymer
Lone pair of electrons on oxygen forms double bond
How are glycogen 1,6 bonds made?
Branching enzyme transfers several terminal residues in a chain to a 6-position of an internal glucose residue;
How do glycogen 1,4 bonds degrade?
Degraded by glycogen phosphorylase
How does branched glycogen degrade?
Residues are removed by glycogen phosphorylase until three 1,4 residues are left next to the 1,6-glycosidic bond;
How do triglycerides degrade?
They are hydrolysed to fatty acids and glycerol by a lipase;
Lipases are activated by glucagon and adrenalin by protein kinase A (same as glycogen degradation).
How much ATP is produced from fatty acid degradation?
14 molecules
What is ketogenesis
Occurs when insufficient glucose is available. This can be due to starvation or diabetes
Under starvation circumstances glucagon signalling promotes gluconeogenesis and fatty acid β-oxidation;
Ketone bodies are âwater-solubleâ versions of fats that can be moved around the body and used as fuels;
Ketone bodies can be converted into propanone (a.k.a. acetone) â produces ketosis (symptom of diabetes).
What does fatty acid degradation produce?
acetyl CoA
What is the upper respiratory system made of?
Nasal cavity
Pharynx
Larynx
What does the upper respiratory system do?
Humidify and warm air
First line of defence
Sensory
Speech
What is lower respiratory system made of?
Trachea
Bronchi
Lungs
What does the lower respiratory system do?
Gas exchange
Defence
Metabolic
What is airway resistance?
proportional to 1/radius4
most resistance is in the large and medium airways
What causes increased airway resistance?
Smooth muscle contraction
Inflamed airway wall
Mucis build up (can cause more infection)
What is the lung epithelium?
Lining cells in airway
Specialisation changes
How are cells specialised in the Bronchi?
Ciliated
Goblet (mucus)
Glandular
How are cells specialised in the Bronchioles?
Ciliated
Non-ciliated
Goblet
Club cells
How are cells specialised in the Alveoli?
Squamous
Cuboidal
The airways are coordinated by
para and sympathetic nervous system
What is the estimated surface area of the airways & airsacs and the alveoli?
50-100cm3
80cm3
What are type 1 alveolar cells?
- large surface area that covers 95% of alveolus and is 10% of cells
- squamous
- gas exchange
What are type 2 alveolar cells?
- cuboidal
- secretory
- precursors for type 1
What is surfactant?
- produced by t2 cells
- mostly phospholipid and protein
- reduces surface tension
- innate immunity function
- given to babies with infant respiratory distress syndrome
How does the lung develop in babies?
- Lung epithelium develops in last trimester (stimuated by corticosteroids in preemies
- foetal lung filled with fluid, must empty rapidly at birth
- c sections can reduce drive for fluid absorption
What is pulmonary circulation?
Artery flows directly from the right ventricle
- LOW oxygen
- HIGH flow
- LOW pressure
Capillaries pass around the alveoli
Pulmonary vein returns oxygenated blood to left heart
What is bronchial circulation?
From aorta (left ventricle)
- HIGH pressure
Supplies oxygen and nutrients the conducting airways
Not involved systemic respiration processes
Only 2% of cardiac outflow
Which three nerves innervate the nervous system?
- Autonomic (bronchial)
- Somatic motor nerves (thoracic intercostal muscles)
- sensory output
How do nerves signals from the lungs reach the brain?
From the vagus nerve to medullary centre
What are slowly adapting receptors?
- Stimulated by stretch receptors in airway smooth muscle
- Shortened inspiration
- Promotion of expiration following steady inflation (prevents over-inflation of lung)
What are rapidly adapting receptors?
- Stimulated by sudden, sustained inflation
- Also by âirritant receptorsâ among epithelium
- Cough
- Mucus secretion
What is the process of a cough reflex?
- Stimulation of irritant receptors (sensory nerves conveys signal to medulla)
- Motor nerves signal to skeletal muscles
- Glottis closes
- Abdominal and internal intercostal muscles contract rapidly
- Intrapulmonary pressure rises
- Glottis opens
What is the membrane surrounding lungs called?
Pleural membrane
- a double membrane separating left and right
- a lubricant
What is the metabolic function of the lung?
- Vascular cells activate angiotensin
- Vascular cells inactivates some circulating hormones
- Club cells detoxify inhaled substances
Neural control
- Central rhythm generator in medulla
- Receptors in respiratory tract causing sneezing, coughing and hyperpnoea
- Nociceptors
Chemical control
- Central and peripheral chemoreceptors which sense oxygen, carbon dioxide and pH levels
How does the medulla control breathing?
Ventral and Dorsal Respiratory Group
- Discharge rhythmically
- efferent neurons to motor nerves
- receives afferent input from periphery and pons
- Little activity in expiratory centre at rest
How does the PONS control breathing?
- Apneustic centre
Prolongs medullary centre firing
Hence depth of breathing increased - Pneumotaxic centre
Inhibits apneustic centre
Controls rate of breathing
What happens to breathing when you transect certain parts of the brain?
Above PONS - loss of voluntary control
Above medulla - loss of feedback sytems
Spinal cord - no breathing
What is the rhythmic discharge of the Pre-Botzinger complex?
- Region of the ventral respiratory group in the medulla
- Spontaneous rhythmic discharge
- Stimulates rhythmic discharge of motor nerves
- Results in contraction of diaphragm
What is Ondineâs curse?
Loss of automatic control
What are the after effects of a lung transplant?
- patient is unable to feel need to cough, or lung congestion
How much oxygen is in atmospheric air?
21%
160 mm Hg
How much carbon dioxide is in atmospheric air?
0.04%
0.3 mm Hg
What chemicals are chemorecpetors susceptible to?
H+ and PCO2
What is the relationship between PCO2 and and pH in CSF?
inversely proportional
How is CO2 regulated during sustainable exercise?
- Ventilation increases prior to rise in blood CO2
- Anticipatory stimulation â higher CNS
- Arterial PCO2 levels fall
- As exercise proceeds, more CO2 generated
- CO2 passes from muscles into venous blood
- Efficiently removed in lung
- When exercise ceases, ventilation falls rapidly
What are three respiratory stimulants?
- Acetazolamide - Carbonic anhydrase inhibitor. Stimulates respiration by creating mild metabolic acidosis, hence reduced acid buffering
- Doxapram - Closes K+ channels
- Caffeine - non-specific CNS stimulation
What are respiratory depressants?
- narcotic analgesics
- barbiturates
- alcohol
What is Haemoglobin?
- a tetramer
- 4 oxygen binding groups
- binding affinity increases with each O2 bound
What is Myoglobin?
- Role in O2 storage and transport in metabolically active cells
- Skeletal and cardiac muscle
- Does not bind cooperatively
- Single O2 binding site, high affinity
- affinity not affected by pH or CO2
How is CO2 transported?
- CO2 transported mainly (70%) as HCO3-
- 7% as dissolved CO2
- 23% as carbamino haemoglobin (HbCO2)
- CO2 from tissues diffuses into plasma
- 85% enters red blood cells and is converted to bicarbonate
- When CO2 production increased (exercise or disease)
- Fraction of CO2 increases relative to HCO3-
What is ventilation-perfusion matching?
For optimum gas exchange, ventilation must match the blood perfusion
What is Hypoxaemia?
- Low blood O2
- Shunting: an area with perfusion but no ventilation
- diffusion abnormalities
- hypoventilation
What is Hypercapnia?
- Increased CO2
- Dead space: ventilation but no perfusion
What are the physiological responses to low inspired O2?
Increased ventilation (immediate)
- Driven by peripheral chemosensors
- Not sustained
Pulmonary vasoconstriction (rapid and sustained)
- Homeostatic mechanism designed to shunt blood away from poorly ventilated areas
- Not useful if the whole lung is hypoxic!
What is acute altitude sickness?
- Lowlanders moving rapidly to altitude >2500m
- Flu-like symptoms, hangover
- Breathlessness
- Hypoxic pulmonary vasoconstriction
- Pulmonary & cerebral oedema (serious!)
What is chronic altitude sickness?
- Low PO2 that cannot be matched by ventilation
- Increased erythropoetin production in the kidney
- Too high haematocrit
- Viscous blood
- Increased load on right heart
- Acetazolamide (carbonic anhydrase inhibitor) inhibits kidney EPO production
- Additional effect to the increased ventilation discussed earlier
What is an MRI Spirolab?
An electric spirometer that compares patient performance based on predicted values
What is forced expiratory volume?
The volume of air you expel in the first few seconds of forcefully exhaling
What is peak expiratory flow rate?
The fastest you can force all air out of your lungs
What is forced vital capacity?
Amount of air exhaled as forcefully as possible after full lungs
What is the important ratio of these values?
FEV1/FVC
What are some contraindications for the FVC test?
Pneumothorax
Unstable cardiovascular status
Thoracic, abdominal, or cerebral aneurysms
Cataracts or recent eye surgery
Recent thoracic or abdominal surgery
Nausea, vomiting, or acute illness
Recent or current viral infection
Undiagnosed hypertension
What is pulse oximetry?
- Non-invasive
- Measures O2 saturation of haemoglobin
(effectiveness of ventilation) - Assesses red and infrared spectrum light transmission through a tissue during pulse flow
- Carbon monoxide or cyanide poisoning
detected as high O2 saturation
What are the diagnoses of different breathing sounds?
Crackles - small airways and alveoli cracking open, infection
Wheeze - COPD and asthma
What is diffusion capacity?
Patient empties lungs
Fills lungs with 0.3% carbon monoxide
Breath held for 10 sec
CO in exhaled breath measured to estimate uptake
What is the pH range of arterial blood?
7.36 to 7.44
What is the approx pH intracellularly?
7.2
What is the most important buffer in the body?
HCO3-/CO2 system
