Physiology Flashcards
Scoring system which is part of the current international consensus definition for sepsis and septic shock?
- SOFA
qSOFA?
- Quick Systemic Organ Failure
- Components: RR, GCS and SBP < 100mmHg
- qSofa > 2 is 10% mortality
Surviving sepsis campaign, compnents? Hour-1 bundle?
- Measure lactate and check again if > 2
- Blood culture before antibiotics
- Broad spectrum abx
- 30ml/kg crystalloid for hypotension or lact > 4
- Vasopressor to aim MAP > 65
Bugs responsible for necrotising fascitis?
- Type (1) - Polymicrobial?
- Staphylococci
- Anaerobes
- Gram negative
- Immunocompromised
Bugs responsible for necrotising fascitis?
- Type (2) - Monomicrobial?
- Beta-haemolytic streptococci group A (S. pyogenes)
- Co-infection with S. Aureus
- Trauma
Options for diagnosis & management of Necrotising Fascitis?
- Fascia biopsy
- Immediate surgery
Pharmacokinetics of antibiotics?
- Dose given reaches Cmax (maximum concentration)
- Distribution & elimination occurs
- MIC reached (Minimal inhibitory concentration).
Minimal inhibitory concentration, properties?
- Concentration must be above MIC
- All beta-lactams work by duration above MIC
Antibiotics of choice in Necrotising fasciitis?
- Vancomycin if MRSA is a concern
- flucloxacillin for staph. Aureus
- clindamycin for streptococci (Good tissue penetration)
Coverage of Clindamycin?
- Anaerobic cover
- Streptococcus
Immunoglobulin as adjunctive therapy in sepsis?
Effective for necrotising fasciitis. InStinct trial (Scandinavian)
AF and SVV?
There is a decrease in SVV with AF
Tricyclic antidepressant overdose and ECG changes?
- Prolonged QRS / QTc
Timing of inflation of intra-aortic balloon should be timed with which portion of the ECG?
Middle of T-wave
Mechanical assist cardiac device, indication?
- Intractable arrhythmias in severe LV dysfunction
- Chronic HF causing renal & hepatic dysfunction
- Intractable angina with poor LV function despite medical & revascularization treatment
- Post-cardiotomy shock
What is the commonest cause of pulmonary HTN?
- Left heart disease
What is the commonest cause of pulmonary HTN?
- Left heart disease
Effect of high respiratory rate on RV and LV?
- This will increase the pre-load of the RV
- It increases LV afterload
- Increased transmural pressures
PEEP & cardiovascular response?
- Decreases transmural pressures
- Reduces RV pre-load
What contributes most to ventilator-induced lung injury?
Plateau airway pressure
Peak airway pressure is related more to ?
Airway resistance
Airway driving pressures will decrease with increasing what ventilator setting?
PEEP
How to calculate driving pressures?
Driving pressures = Plateau pressures - PEEP
Calculation of compliance ?
Compliance = Volume / Driving pressure
Calculation of CO2 gap?
CO2 gap = PaCO2 - ETCO2
Conditions causing increased CO2 gap?
- PE
- Dead-space ventilation
- Low filling status - Needs fluid resuscitation
Uses of Esophageal pressure monitoring?
- Used to assess whether ventilation is lung-protective
- Measures estimated pleural pressure
- It can measure patient’s work of breathing
NAVA (Neurally-Adjusted Ventilator Assist)? Functions & uses?
- Measures the electrical activity of the coastal diaphragm
- Allows for proportional ventilation
Wasted effort can be illustrated using what diagram?
The campbell diagram
Improve patient - ventilator interaction?
- Increasing trigger sensitivity
Factors affecting cardiac output?
- Pressure within the venous system
- Capacitance of the venous reservoir
- The resistance to venous return
- Peripheral distribution of the blood flow
What is Cardiac output?
CO = HR x SV
Factors influencing SV?
Preload, contractility & afterload
Factors influencing SV?
Preload, contractility & afterload
Factors influencing SV?
Preload, contractility & afterload
Preload dependent on ?
Venous return
Afterload dependent on?
Arterial pressure
What is CVP?
- Equivalent to the RA pressure
- Filling pressure of the right side of the heart
- Determinant of cardiac function
- It is a key determinant of venous return
Venous valves in the thorax?
There are no venous valves in the thorax
Factors increasing CVP?
- Increased circulating volume
- Decreased venous capacitance
- Increased venous tone (vasopressors)
- Decreased cardiac function (HF/Obstructive acute HF - PE/Tamponade)
Etiology of shockable rhythms?
- IHD/ AMI
- Electrolyte abnormalities
Etiology non-shockable rhythms?
- Hypovolaemia
- Hypoxia
- Hypothermia
- Electrolyte abnormality
- PE
- Tamponade
- Tension PTX
- Trauma & Toxins
- AMI
Etiology non-shockable rhythms?
- Hypovolaemia
- Hypoxia
- Hypothermia
- Electrolyte abnormality
- PE
- Tamponade
- Tension PTX
- Trauma & Toxins
- AMI
Factors causing falsely elevated oxymetry readings?
- Carboxy-haemoglobin
- Met-haemoglobin
Factors causing falsely low oxymetry readings?
- Ambient light
Location of the respiratory centre?
Medulla oblongata
Location of the respiratory centre?
Medulla oblongata
Functions of the central chemoreceptors?
- ## Directly senses CO2 changes (conc. of hydrogen ions in the CSF)
Location of peripheral chemoreceptors?
- Carotid
- Aortic arch
Function of peripheral chemoreceptors?
- Sense PO2
- Sense change in pH of blood
Calculation of PaCO2?
PaCO2 = CO2 production / Minute volume
Calculation of alveolar ventilation?
Alveolar ventilation = RR x (Tidal volume - Dead-space)
Effective tidal volume diminishes with increased RR
What is dead-space ?
- Volume not participating in gas exchange
What are the different components of dead-space?
- Anatomical dead-space (2ml/kg)
- Alveolar dead-space
- Instrumental dead-space
Physiology of alveolar dead-space?
- Ventilated but not perfused
- Increased arterial CO2 due to lack of excretion via the lungs
Causes of alveolar dead-space?
- PE
- Hypoperfusion
- Intrinsic PEEP
Calculation for measuring dead-space?
VD/VT = PaCO2 - PeCO2 / PaCO2
PeCO2 - Mixed expired CO2
Causes of hypercapnia ?
- Low minute volume
- Increased dead-space
- High CO2 production
Potential systems which could be affected that causes hypercapnia?
- CNS
- PNS
- Respiratory muscles
- Chest wall and pleura
- Upper airway
- Lungs
What is the alveolar gas equation?
PAO2 = FiO2 x (P.atm - P. H2O) - PaCO2 / RQ
Ex;
PAO2 = 0.21 x (760 mmHg - 47) - 40 / 0.8 = 100 mmHg
PACO2 = Alveolar O2
gases and vapors in the alveolar?
- Nitrogen
- Oxygen
- CO2
- Water vapor
Hypoxia & altitude ?
The atmospheric pressure is lower at higher altitude hence low amount of FiO2
Hypoxia & altitude ?
The atmospheric pressure is lower at higher altitude hence low amount of FiO2
Causes of hypoxia?
Elevated A-a gradient
- Shunt (A-a gradient elevated)
- V/Q mismatch (A-a gradient elevated)
Low A-a gradient
- Altitude (A-a gradient low)
- Hypoventilation (A-a gradient low)
- High CO2
- Diffusion limitations ( Rare ) - Chronic lung disease / COPD
What is shunting ?
This is volume of blood not taking part in gas exchange
Anatomic shunt?
- Normally < 5% in healthy individuals
- No response to increased FiO2
Venous admixture or low V/Q (Shunt)?
- Improves with increase FiO2
- Chemo-sensors prevent admixture by Hypoxic vasoconstriction
Physiology of hypoxic vasoconstriction?
- Low Oxygen levels detected inside the alveolar
- Capillary vasoconstriction occurs
- Blood diverted to more well oxygenated capillaries
Calculation of A-a gradient ?
- It should normally be very low
A-a gradient = PAO2 - PaO2 = FiO2 x (P.atm - P.H2O) - PaCO2 -PaO2 / RQ
Shunt equation?
See EDIC notes
Shunt equation?
See EDIC notes
Treatment for MH?
Dantrolene
Temperature is higher in pyrexia or hyperthermia?
Higher in hyperthermia
Hyperthermia?
- Temperatures higher than pyrexia
- Thermoregulatory mechanisms are lost
- Temperatures usually > 41.3 degrees Celsius
Where is thermoregulation processed ?
At the hypothalamus
Definition of fever ?
Core temperature > 38.3 degrees Celsius
Pyrexia and thermoregulatory mechanisms?
Thermoregulatory mechanisms are preserved
What chemical results in an elevated temperature setpoint in the brain?
PGE2 in the CNS
Total body mass constitution?
- Made up of 60% of water
Total body fluid is divided into ?
- 2/3 intracellular fluid
- 1/3 Extracellular fluid
The ECF is divided into?
- Interstitial fluid = 80%
- Plasma = 20%
Intracellular compartment volume?
25 litres
Extracellular compartment volume?
17L
What are the intracellular electrolytes ?
- Potassium = 140mEq/L
What are the extracellular electrolytes ?
- Sodium = 140mEq/L
Osmolality of the fluid compartment?
280 mOsm/kg
Units of hydrogen ion concentration ?
nmol/L (Nano-moles / Litre)
Normal hydrogen ion concentration ?
40 nmol/L
Acuity of liver failure?
Hyper-acute = < 7 days (Drugs induced or hypoxia)
Acute = 7 - 28 days ( Autoimmune or drug related)
Sub-acute = > 28 days (Unknown cause)
KCH criteria to identify patient’s at risk of death from liver failure?
- PT > 100s & INR > 6.6 ( + Encephalopathy)
KCH criteria to identify patient’s at risk of death from liver failure? Any three out of 5 criterias? (+ Encephalopathy)
- Age: < 10 or > 40
- Bilirubin > 300
- Duration of jaundice before the onset of encephalopathy > 7 days
- PT > 50s or INR > 3.5
- Non-hepatitis A or B / drug induced
Scoring systems in liver failure?
- MELD
- APACHE II
- CLIF-SOFA
- Child-Pugh Score
Scoring systems in liver failure?
- MELD
- APACHE II
- CLIF-SOFA
- Child-Pugh Score
Primary (hepatic) causes of acute liver failure?
- Drug related
- Viral hepatitis
- Toxin induced ALF
- Budd-Chiari syndrome
- Autoimmune
- Pregnancy related
Secondary (extra-hepatic) causes of ALF?
- Ishcaemic hepatitis
- Haemophagocytic syndrome
- Metabolic disease
- Infiltrative disease
- Lymphoma
- Infections (e.g malaria)
Primary causes of chronic liver disease?
- Wilson’s disease
- Autoimmune
- Budd-Chiari
Seconadary causes of chronic liver disease ?
- Liver cancer
- Alcoholic hepatitis
Hypoxamia mechanisms ?
- inadequate fio2
- inadequate delivery to target organ
What is the oxygen cascade?
Transfer of oxygen from the environment to the alveoli and subsequently arterial blood.
Oxygen cascade & oxygen content?
Reduction in oxygen tension from the environment to arterial blood.
Main factors causing hypoxia ? See individual breakdown of the below points ……
- low fio2 (altitude, hypoxic gas mixture)
- Alveolar hypoventilation
- diffusion impairment
- V/Q mismatch & shunt
Consequence of alveolar hypoventilation?
- decrease in V/Q
- A-a gradient is usually normal
Causes of pulmonary diffusion impairment?
- Increased thickness of alveolar membrane (fibrosis)
- Decrease in capillary transit time ( severe sepsis)
- Decrease in capillary blood volume (hypotension)
Variation of V/Q from base to apex?
0.6 - 3.0
V/Q mismatch causing hypoxia?
- Reduction of ventilation relative to perfusion (low V/Q).
Hypoxic pulmonary vasoconstriction?
Physiological pulmonary vasoconstriction will reduce blood flow to poorly ventilated alveolar units, thus a shunt
Atmospheric pressure at sea level?
101.3 kPa
Calculation of atmospheric PO2?
PO2 = FiO2 x Atmospheric pressure
Outline processes of the oxygen cascade ?
- inspired oxygen
- Trachea - humidification
What is hypoxaemia?
This is low arterial oxygen tension occuring due to pathology in transfer of oxygen from the atmosphere to the left side of the heart.
Hypoxia is a consequence of either ?
- Inadequate arterial oxygen tension
- Inadequate delivery of oxygen to the end organ
Inspired oxygen within the oxygen cascade?
- FiO2 is 21% in RA
- Atm pressure 101.3 kPa at see level
- PO2 = FiO2 x Atm pressure
- Pathologies - Altitude , hypoxic gas mixture
Trachea in the oxygen cascade?
- Humidification
- Saturated vapour pressure of water - 6.3 kPa @ 37 degrees
- PO2 = FiO2 (Atm pressure - SVP H2O)
- Normal PO2 19%
Alveoli in the oxygen cascade?
- Ventilation
- Normal PACO2 5.3 kPa
- Alveolar gas equation is used to calculate PO2 (Google it)
- Hypoventilation will cause hypoxia
Pulmonary capillary in the oxygen cascade?
- Diffusion
- The rate of diffusion across the alveolar member determined by Fick’s law
- A - a gradient = PAO2 - PaO2
- Pathologies; Emphysema, fibrosis & Oedema
Artery in oxygen cascase?
- Admixture / shunt
- Oxygenated blood from the lungs mixes with deoxygenated blood in the left heart (<3%)
- Admixure arises physiologically from Thebesian and bronchial veins.
- Pathologies; Intra-cardiac or intra-pulmonary shunts, ARDS, effusion, PTX
- Oxygen content = (SPO2 x Hb x 1.34) + 0.003 x PO2
Hypoxia corrected with increasing FiO2?
- V/Q mismatch
- Diffusion impairment
- Alveolar hypoventilation
- Low inspired oxygen
Hypoxia with normal A-a gradient?
- Alveolar hypoventilation
- Low inspired oxygen
Hypoxia with normal shunt fraction?
- Diffusion impariment
- Alveolar hypoventilation
- Low inspired oxygen
The P50?
Represents the PaO2 at which Hb is 50% saturated
Properties of oxygen?
- ## Low solubility in plasma
Haemoglobin and ODC?
- Affinity for oxygen increases with every molecule of oxygen it binds
- Left shift of the curve - Increases Hb affinity for oxygen
Factors determining left-ward shift of the ODC?
- Decreased temperature
- Decreased CO2
- Decreased 2,3-DPG
- Increased pH
Factors determining right shift of ODC?
- Increased temperature
- Increased arterial CO2
- Increased 2,3-DPG
- Decreased pH
Determinants of oxygen delivery (DO2)?
- Transfer of oxygen from atmosphere to blood
- Carriage of oxygen in blood bound to Hb
- Systemic blood flow (Cardiac output)
Oxygen delivery flux equation?
DO2 = CO (SaO2 x Hb x 1.34) + 0.003 x PO2
Classification of hypoxia?
- Hypoxaemic hypoxia - Low arterial oxygen tension
- Anaemic hypoxia - Low Hb or impaired (Methaemoglobinaemia, carbonmonoxide poisoning)
- Stagnant hypoxia - Low cardiac output
- Cytotoxic hypoxia - Abnormal cellular utilization of oxygen. Failure of aerobic respiration (Cyanide poisoning)
Properties of carbondioxide?
- About 22 times more soluble than oxygen
- Affected only by ventilation - Alveolar CO2 and minute ventilation are directly related
Components of dead-space?
- Anatomical dead-space
- Alveolar dead-space
- Physiological dead-space
Anatomical dead-space?
- Consists of the conducting airways
- Do not contribute to gas exchange
- Its approximately 2ml/kg
- Reduced by ETT
- Fowler’s method is used to measure anatomical dead-space
Alveolar dead-space?
- Proportion of tidal volume entering the alveolar - Not perfused
- Increased in disease
- Present in PE & low cardiac output state
Physiological dead-space?
- Combination of anatomical and alveolar dead-space
- Calculated using the Bohr’s equation
What is the Bohr’s equation?
- Used to calculate physiological dead-space
- VD/VT = PaCO2 - PeCO2 / PaCO2
Lung volumes?
- IRV = 2500mls
- TV = 500mls
- ERV = 1500mls
- RV = 1500mls
- TLC = 6000mls
- VC = 4500mls
Calculation of alveolar MV?
- (TV - dead-space) x RR =
- Main determinant of Mv is arterial CO2
- Central chemoreceptors in the medulla detect changes in pH associated with changing CO2
- PO2 becomes a determinant of MV only in hypoxia
Barriers to infection and percentage of protection?
- Physical barriers (99%)
- Innate immune response (0.9%)
- Adaptive immune response (0.1%)
Components of physical barriers to infection?
- Skin
- Cilia
- Acidity
- Lysozomes
- Normal bacterial flora
Components of innate immune response?
- Neutrophils
- Mast cells
- Macrophages
- NK cells
- Complements
- Acute phase
Components of Adaptive immune response?
- B-lymphocytes
- T-lymphocytes
Causes of dynsfunction to physical barriers? skin
- Burns
- Trauma
- Steven-Johnson’s Syndrome
- Kartagener’s
- Prolonged antibiotics
Causes of dysfunction to innate immune response?
- Wiscott-Aldrich
- Leucocyte adhesion defect
- Complement defect
- Steroids
- TNF-alpha inhibitors
- Chemotherapy
- Diabetes
- SLE
- Liver failure
- Malignancy
Causes of dysfunction to adaptive immune system?
- Hypogammaglobinaemia
- DiGeoge’s syndrome
- Common variable immunodeficiency
- Lymphoma
- HIV
- Chemotherapy