Primary Flashcards
non-hypoxic causes
of pyruvate accumulation
which include; circulating catecholamines, exercise, sepsis or lack or mitochondria (RBCs)
-2020 first sitting question 8
‘lactate sink’
, allowing a period of ongoing ATP production from glycolysis when cells become oxygen deplete or the Kreb’s cycle is inhibited;
-2020 first sitting question 8
, allowing a period of ongoing ATP production from glycolysis when cells become oxygen deplete or the Kreb’s cycle is inhibited;
‘lactate sink’
-2020 first sitting question 8
HO- CO - COH -CH3
Lactic Acid
-2020 first sitting question 8
Lactate production
2 main categories
Production:
• It is produced by anaerobic metabolism of pyruvate either:
o Physiologically → in RBC (no mitochondria), renal medulla (↓ PO2), cornea/ lens (↓PO2) → hence, normal plasma [lactate] is 0.5-2 mmol/L (and NOT zero!)
o Pathologically → reduced tissue perfusion and/or O2 delivery (Eg. shock, hypoxaemia) →thus, plasma [lactate] ↑↑↑ (> 2 mmol/L)
-2020 first sitting question 8
Lactate can be used as a fuel source from
Used as a fuel source by the heart and brain
-2020 first sitting question 8
Lactate can be Transported to the liver where it is:
▪ Converted back to glucose via gluconeogenesis (requires 6x ATP), which is then
transported back peripherally for use → “Cori cycle”
▪ Converted to pyruvate intermediate → utilized locally in TCA cycle for ATP production via oxidative phosphorylation
-2020 first sitting question 8
What is the Cori cycle
Lactate is Converted back to glucose via gluconeogenesis (requires 6x ATP), which is then
transported back peripherally
-2020 first sitting question 8
How many ATP involve in converting lactate back to glucose
6
-2020 first sitting question 8
What happens to lactate with the Resolution of hypoxia
Resolution of hypoxia (Ie. tissue O2 tension restored) → intracellular lactate can be oxidised
back to pyruvate for use in local tissue aerobic metabolism (Ie. fed into TCA cycle)
-2020 first sitting question 8
what is the lactate sink
Lactate Sink:
• Lactate acts as a sink in heart, liver, muscle etc, allowing a period of ongoing ATP production
from glycolysis when:
o cells become oxygen deplete
o Kreb’s cycle is inhibited
o Other causes of pyruvate accumulation: circulating catecholamines, exercise, sepsis or
lack of mitochondria (RBCs
-2020 first sitting question 8
Lactate can be Intracellular shuttle:
▪ mitochondrial membrane
▪ peroxisomes
-2020 first sitting question 8
What are type 1 and type 2 muscle fibers
slow-twitch (red) and fast-twitch (white) respectively
-2020 first sitting question 8
in pregnancy what happens to
Oral absorption
gastric absorption
intestinal absorption
↓ Oral absorption
↑ gastric absorption
↓intestinal absorption
-2020 first sitting question 9
in pregnancy what happens to cardiac otuput
increases 30-40%
-2020 first sitting question 9
What happens in pregnancy to Inhalational absorption?
increases
• Progesterone-mediated ↑ MV (by 50-70%)
-2020 first sitting question 9
In pregnancy what causes a change to minute ventilation?
• Progesterone-mediated ↑ MV (by 50-70%)
-2020 first sitting question 9
What happens in pregnancy to minute ventilation
increases
• Progesterone-mediated ↑ MV (by 50-70%)
-2020 first sitting question 9
what happens to VD in pregnancy
• ↑ VD
• ↑ TBW/ECF (by 50%) (important for polar/ionized drugs)
-2020 first sitting question 9
what happens to body fat in pregnancy
• ↑ body fat % (important for lipid soluble drugs)
-2020 first sitting question 9
what happens to plasma protein in pregnancy
• ↓ plasma protein 2° to dilutional effect
-2020 first sitting question 9
what happens to albumin in prengnacy
• ↓ albumin →
• ↑ free % of acidic drugs (Eg. STP, propofol)
• ↓ dose required
• ↑ transplacental transfer of drug.
-2020 first sitting question 9
what happens to A1AGP in pregnancy
• ↓ A1AGP (by 30%) →
• ↑ free % of basic drugs (Eg. LA, β blockers)
• ↓ dose required
• ↑ transplacental transfer of drug
-2020 first sitting question 9
in pregnancy do you get a
metabolic vs respiratory
acidosis vs alkalosis
• Ionisation (mild ↑pH alters ionisation based on pKa)
• ↑ MV = mild respiratory alkalosis
↑ transplacental transfer of basic drugs as they will have ↑ % in
unionized form
• (Base in base is less ionised)
• ↑ ion trapping in more acidotic foetal circulation
-2020 first sitting question 9
in pregnancy what happens to the Progesterone:oestrogen ratio
• Progesterone:oestrogen ratio
-2020 first sitting question 9
Effect of Progesterone and Oestrogen on hepatic hepatic enzymes
• Progesterone → induces hepatic enzymes
• Oestrogen → inhibits hepatic enzymes
-2020 first sitting question 9
what happens to plasma cholinesterase in preganancy
• ↓ plasma cholinesterase (30%)
-2020 first sitting question 9
can the Placenta metabolise drugs?
• Placenta metabolises some drugs
-2020 first sitting question 9
does the Foetal liver have a functioning CYP450?
• Foetal liver has functioning CYP450
• Can metabolise drugs
• But requires transfer back to maternal circ for conjugation
-2020 first sitting question 9
what happens to RBF/GFR in pregnancy
• ↑ RBF/GFR (50%)
• ↑ clearance/↓ elimination t1⁄2 of water-soluble drugs
-2020 first sitting question 9
what happens to MV/FRC in pregnancy
• ↑ MV/↓FRC
• ↑ washout of volatile agents
-2020 first sitting question 9
what happens to MAC in pregnancy
• Decreased MAC – Increased sensitivity to volatile anaesthetics
-2020 first sitting question 9
what happens to LA sensitivity in prengancy
• Increased LA sensitivity due to decreased α1-glycoprotein
-2020 first sitting question 9
what hapepns to sensitivity to IV anaesthetics in pregnancy
• Increased sensitivity to IV anaesthetics
-2020 first sitting question 9
Cardiac output measurement can be performed:
INVASIVELY
o Pulmonary Artery Catheter
▪ Thermodilution
▪ Fick Principle
o Indicator Dilution Technique
o TOE
o Arterial waveform analysis
▪ PiCCO
▪ Vigileo
Non-invasively
o TTE
o MRI
o Thoracic impedance
cicm wrecks 2017-2-10
Cardiac output Definition
Cardiac output is defined as the volume of blood ejected by the heart per unit time.
It is usually presented as [stroke volume × heart rate], in L/min
Deranged 2014 march
The equation for thermodilution measurement
• This uses the equation, V̇ = m/Ct, where:
o V̇ = flow, or cardiac output
o m = dose of the indicator,
o C = concentration, and
o t = time
Deranged 2014 march
