Paper 2 Flashcards
What is the equation for compliance?
Compliance = change in volume/change in pressure
What is specific compliance related to?
The FRC, not total lung capacity
What are the normal values for lung compliance vs total thoracic compliance?
85-100 ml/cmH2O Total thoracic compliance
200ml/cmH2O Lung compliance
Do children or adults have higher compliance?
Adults
What factors will increase compliance?
- surfactant
- emphysema
- old age
- acute asthma
What factors reduce compliance?
- pulmonary fibrosis
- pulmonary venous engorgement
- pulmonary oedema
- ARDS
- neonates
- extremes of lung volume
- pneumonia
- chronic bronchitis
What is closing capacity?
Lung volume at which airway closure occurs
= closing volume + residual volume
It is about 10% of vital capacity but increases gradually with age until it is about 40% of VC aged 65yrs
When does airway closure take place?
When closing capacity equals or exceeds the FRC
What factors increase closing capacity?
- Asthma
- Raised intrathoracic pressures
- Smoking
CC may also encroach on FRC when FRC is reduced such as Pregnancy, Obesity, General anaesthesia
How do you measure closing capacity?
Fowler’s method - nitrogen or helium concentration analysis.
Phase 1 = dead space gas, no nitrogen/helium present
Phase 2 = Mix of dead space and alveolar gas with some marker gas
Phase 3 = Plateau of alveolar gas
Phase 4 = Closure of upper airways causing a rise in marker gas = closing volume
In dead space, what happens to the alveolar PCO2?
It will be approaching O kPa
In dead space, what happens to the end-capillary PCO2?
It approaches 0KPa
Where is a high V/Q ratio found in the lungs?
At the top of the lungs
What is the P50?
It is the partial pressure of O2 at which Hb is 50% saturated.
3.5 kPa normally
What will reduce the P50?
Left shift = increased O2 affinity (P50 <3.5 kPa)
- reduced PaCO2
- alkalosis
- hypothermia
- reduced 2,3, DPG
- CO
- MetHb
- Fetal Hb
What will cause a right shift in the P50?
RIght shift = reduced O2 affinity = P50 >3.5kPa
- elevated PaCo2
- acidosis
- hyperthermia
- elevated 2,3 DPG
- pregnancy
- haemoglobin S
- altitude
What is the Bohr effect?
The shift of the oxyHb curve to the right in response to a rise in PaCO2 or fall in pH
What is the haldane effect?
The phenomenon where deoxygenated Hb has a higher affinity for CO2 than oxygenated Hb
What does the x descent represent?
The fall in atrial pressure as the ventricle contracts - this lengthens the atria and causes a pressure drop
What is the y descent?
Once the mitral valve opens, blood flows into the ventricle from the left atrium, causing a pressure drop in the atrium
What is the Donnan effect?
This describes the phenomenon where charged particles that cannot diffuse across a membrane have an effect on the distribution of other charged particles.
Proteins and phosphates hold negatively charged molecules inside the cell, thus the inside is negative with respect to the outside and these cannot cross the cell membrane.
During exercise, how are the cardiovascular changes brought about?
By a change in autonomic nerve activity.
There is an increase in sympathetic drive and reduction in parasympathetic activity.
There is a rise in plasma catecholeamine levels but this contributes less to the overall cardiovascular changes.
What increases more in exercise, HR or SV?
Heart rate.
Because the stroke volume is limited by the size of the heart chambers and the time available for filling and ejection.
What is required to calculate capillary membrane permeability?
- rate of solute transfer
- membrane area
- concentration difference across the wall
How can solute diffusion rate be measured?
Directly by optical methods (eg cannulated capillaries perfused with dyes).
Indirectly by the Fick Principle- calculates whole organ transfer of rapidly diffusing solutes across the whole microvascular bed.
What can radiolabelled albumin be used to measure?
Recording the extravascular accumulation of radiolabeled albumin after intravascular injection can assess capillary permeability to plasma macromolecules.
What transport method is used for water and solutes across capillary walls?
This is a passive process, down concentration gradients
What is autoregulation of the kidney affected by?
- changes in resistance of the interlobular arteries as well as resistance in afferent and eferent arterioles of the cortical nephrons
- not affected by changes in resistance of the larger interlobar arteries
What is the driving force for water reabsorption in the proximal tubule?
The main driving force is sodium reabsorption, followed by Cl and HCO3 reabsorption.
This creates a small osmotic gradient along which H2O passively diffuses out (isotonic reabsorption).
So the main drive in the proximal tubule is Na+ reabsorption.
What is the tonicity of fluid reaching the tubular fluid after the LoH?
Because the LoH ascending limb is relatively impermeable to water, the tubular fluid becomes HYPOTONIC (as NaCl is actively transported into medulary extracellular fluid)
Where is aldosterone produced?
In the adrenal cortex - zona glomerulosa
Which is the most important mineralocorticoid?
Aldosterone.
The main function of mineralocorticoids is to regulate transport of Na+ and K+ in the kidney and other organs such as the intestine, gallbladder and salivary glands.
What is cholesterol the precursor for?
- synthesis of sex hormones (testosterone, progesterone, oestradiol)
- glucocorticoids (cortisol)
- mineralocorticoid aldosterone
When is aldosterone secretion highest and lowest?
Lowest in the evening and highest early in the morning. This diurnal variation applies to R-A-A as a whole and involves changes in posture, stress and melatonin secretion
What will stimulate release of aldosterone?
- reduced blood volume
- hyperkalaemia
- hyponatraemia
How does a high protein diet cause a metabolic acidosis?
This will result in increased production of hydrochloric acid and sulphuric acids
What does incomplete oxidation of carbohydrate do?
This causes a metabolic acidosis, because it results in the anaerobic production of lactic acid
What does an increased metabolism of organic anions do?
Results in a metabolic alkalosis due to increased metabolism of organic anions such as lactate and citrate to CO2 and H2O
What does an increased intake of alkaline substances do to your acid-base balance?
It causes a metabolic alkalosis
What does a diet high in vegetable matter do?
Produces a large amount of HCO3-, which is excreted in the urine, making it alkaline
What does the mucosa of the stomach contain?
- chief cells
- parietal cells
- endocrine cells
- mucus producing cells
WHat is the rate of stomach emptying dependent on?
- stomach signals from nervous stimulation caused by distension and the hormone gastrin, which is secreted by the antral mucosa - this increases pyloric pumping force and inhibits the pylorus - promoting stomach emptying
- signals from the duodenum depress the pyloric pump and increase pyloric tone
What does gastrin do?
Causes secretion of acidic gastric juices by the stomach and has a stimulatory effect on motor functions of the stomach to enhance the activity of the pyloric pump and increase gastric emptying.
What bilirubin concentration does jaundice develop at?
Plasma bilirubin concentrations > 18micromol/L
What is pre-hepatic jaundice?
Increased production of bilirubin (eg due to excess haemolysis, when increased production far exceeds the liver’s capacity to conjugate bilirubin).
Therefore excess unconjugated bilirubin in plasma.
What can cause hepatic jaundice?
- damaged hepatocytes
- inflammation of liver cells (hepatitis)
- deficiency of glucuronyl transferase (gilbert’s syndrome) - which is the enzyme responsible for conjugation of bilirubin for further metabolism
What forms of hepatic jaundice result in dark urine?
- hepatocellular damage
- Dubin-Johnson syndrome
- all forms of post hepatic jaundice
- the cause of dark urine is elevated levels of the conjugated, water soluble form of bilirubin
What causes post hepatic jaundice?
Obstruction to the bile ducts by stones or tumour - causes increased levels of conjugated bilirubin in the blood.
There is very little bilirubin that enters into the intestine in post-hepatic jaundice. The intestine is where bilirubin is broken down by bacteria to stercobilinogen, which is then oxidised to stercobilin.
Stercobilin = brown colour of faeces (low levels therefore = pale stools)
What factors increase blood flow to the liver?
- food
- acute hepatitis
- supine posture
- enyzme inducing drugs
What factors decrease blood flow to the liver?
- positive pressure ventilation
- hypoxia
- hypercarbia
- abdominal surgery
- ganglion blocking drugs
- vasopressin
- volatile anaesthetics
What is fever?
Fever is an abnormally high body temperature and the most frequent cause is infection by bacteria or viruses.
Prostaglandins released by phagocytes reset the hypothalamic thermostat to a higher temperature. Temperature regulating reflex mechanisms then bring the body temp up to the new setting, therefore causing a high temp.
What is heat exhaustion?
- normal body temp
- profuse perspiration
- cool and clammy skin
- symptoms
- dizziness
- muscle cramps
- vomiting
- fainting
- due to loss of fluids and electrolytes
What is heatstroke?
Occurs when temperature and relative humidity are high, making it difficult for the body to lose heat by radiation, conduction or evaporation.
Blood flow to skin is decreased and perspiration is reduced resulting in body temp increasing.
Why are the elderly more prone to hypothermia?
They have reduced metabolic response to lower temperatures and a reduced perception of cold as well as hot temperatures.
How do macrophages cause fever?
They release interleukins 1 and 6 (IL1 and IL6) once they become active during inflammation and infection.
These promote synthesis of proteins in the liver that act as pyrogens to generate fever.
What does insulin do?
Main action is to decrease blood glucose levels by:
- increasing transport of glucose from blood into cells
- increasing glycogenesis (glucose into glycogen)
- increasing lipogenesis (glucose into fat)
- decreasing glycogenolysis (glycogen into glucose and glucose 1 phosphate)
- reducing gluconeogenesis (formation of glucose from non-carbohydrate substances such as lactate)
- increasing protein synthesis
What causes insulin secretion?
- high blood glucose
- increased blood levels of amino acids
- hGH raises glucose concentration which then stimulates insulin
- ACTH increases plasma glucose concentrations which then stimulates insulin release
- somatostatin inhibits insulin release
- increased parasympathetic activity stimulates insulin release
How does body temperature affect cerebral blood flow?
For each degree celcius decrease in body temp there is a 5% decrease in CBF
How do volatile anaesthetics affect cerebral blood flow?
They increase CBF via a vasodilatory effect
How does pCO2 affect cerebral blood flow?
Between a PaCo2 of 2.7 - 10.7 kPa there is a linear increase in CBF by approximately 2-4% for each 0.13 kPa (1mmHg) in PaCO2.
What what PaO2 would cerebral blood flow increase?
PaO2 < 6.7 mmHg
What drugs will affect cerebral blood flow?
Opioids - no effect
Thio/propofol/benzodiazepines/etominate - decrease
Ketamine - increases
What affects hepatic extraction ratio?
- hepatic blood flow (drug delivery)
- free or unbound drug fraction (fraction of drug that can interact with hepatic enzmes)
- intrinsic metabolic capacity of enzymes represented by Michaelis-Menton constants, accounting for the intrinsic ability of liver enzymes to metabolise individual substances in the absence of flow or protein binding restrictions
- pKa and lipid solubility have no direct effects on hepatic extraction ratio
What does a high hepatic extraction ratio mean?
High HER (>0.7) is “flow dependent clearance” - high metabolic capacity for a drug causes rapid removal of free drug from the circulation.
This clearance is independent of protein binding, but highly dependent on hepatic blood flow.
Eg propofol, ketamine, morphine and lidocaine
What is low hepatic extraction ratio?
Low HER (<0.3) - capacity limited clearance - low metabolic capacity means even if there is low protein binding, enzymes saturate rapidly and a concentration gradient between plasma and hepatocytes is eliminated rapidly.
Clearance is independent of hepatic blood flow.
Eg warfarin, phenytoin, diazepam
What is an intermediate hepatic extraction ratio?
Intermediate HER (0.3 - 0.7) - clearance is affected by changes in protein binding metabolic capacity and hepatic perfusion.
Examples include aspirin and codeine.
What is the time constant inversely proportional to?
The rate constant (k) and clearance (Cl). It’s directly proportional to the volume of distribution.
time constant = Vd/Cl
Which drugs undergo zero order kinetics?
- Phenytoin
- Ethanol
- Salicylates
- Thiopentone
- Theophylline
Which drugs bind to albumin?
Albumin is a basic protein and binds acidic and neutral drugs
- warfarin
- NSAIDS
- phenytoin
- diazepam
- thiopentone
- propofol