Week 4 Flashcards by Hamish T

Small arteries and arterioles are the greatest contributor to ___ ___ ___.

Total peripheral resistance

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Normal end-systolic volume is approx. ___ mL and normal end-diastolic volume is approx. ___ mL.

Normal ESV - approx. 75 mL

Normal EDV - approx. 150 mL

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For any given volume of blood, ventricular pressure depends on ___ of the wall (diastole) and ___ ___ in the wall (systole).

Compliance of wall - diastole

Active tension in wall - systole

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The ___ ventricle is thicker and ___ compliant than the right ventricle.

Left is thicker and less compliant c.f. right

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Stroke volume can be increased by increasing end ___ volume and increasing ventricular ___.

Increase end diastolic volume

Increase ventricular contractility

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The ___ nervous system can increase contractility by the ___ nervous system has NO major role in contractility.

SNS can increase contractility

PNS - NO major role in contractility

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If contractility ___ or if compliance ___, then pressure generated at any given volume is increased.

Contractility increases

Or compliance decreases

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Afterload is the load encountered by the ventricle as it commences contraction. Afterload is a ___ load due to arterial hypertension or an LV outflow tract obstruction.

Pressure

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Preload is the stretch on myocyte fibres before they commence contraction. Preload is a ___ (___-___ ___) load due to increased ___ ___.

Preload is a volume (end-diastolic volume) load due to increased venous return

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Arteries are ___ compliant than veins.

Less

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You increase blood in systemic arteries by ___constriction, and NOT by decreasing ___ ___ or decreasing ___ ___ ___.

Increase blood in systemic arteries by venoconstriction

NOT by decreasing cardiac output or decreasing total peripheral resistance

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65% of total blood volume is in systemic ___, 13% of total blood volume is in systemic ___ and 5% of total blood volume is in systemic ___.

65% in systemic veins
13% in systemic arteries
5% in systemic capillaries

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In autotransfusion, there is ___constriction to increase volume in arteries if ___ ___ is too low.

Venoconstriction to increase volume in arteries if blood pressure is too low

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What is the definition of mean circulatory filling pressure?

It is the mean vascular pressure that exists after a stop in cardiac output and redistribution of blood, so that all pressures are the same throughout the system

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Mean circulatory filling pressure depends on ___ of blood and ___ of vessels. Mean circulatory filling pressure is approx. ___ mmHg.

Depends on volume of blood and compliance of vessels

Approx. 7 mmHg

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Venous pressure ___ as cardiac output increases.

Decreases!

Heart fills with venous blood to increase CO, so venous pressure decreases

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If venous pressure drops under ___ pressure, then superficial veins will collapse.

Atmospheric

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___ ___ ___ is the pressure in the great veins (SVC/IVC) outside the heart, and is slightly higher than ___ ___ pressure.

Central venous pressure (approx. 1-5 mmHg)

Slightly higher than right atrial pressure

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Bradykinin mediates dilation by acting on ___, but mediates constriction by acting on ___ ___ directly.

Dilation - endothelium

Constriction - smooth muscle

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Antagonist potency is mostly determined by ___.

Affinity

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Antagonists may be ___ (binds to same site as agonist) or ___-___ (may bind at receptor, or at other sites).

Competitive

Non-competitive

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In the context of allosteric modulation, the GABA binding site on the GABA(A) receptor is called the ___ site.

Orthosteric

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___ bind to the allosteric site on the ___ receptor to increase binding of its ligand resulting in ___ and decreased brain activity.

Benzodiazepines
GABA(A) receptor
Hyperpolarisation

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Receptor active/orthosteric sites are usually conserved, but there is no evolutionary conservation of ___ binding sites. Therefore, there is significant selectivity between different allosteric receptor subtypes - useful for drug design.

Allosteric

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Allosteric antagonists produce incomplete ___ so that physiological modulation can continue.

Antagonism

If a competitive reversible antagonist doesn't change the maximum response to an agonist, it is a ___ antagonist.

Surmountable

While propranolol (beta adrenoceptor antagonist) can be surmounted by a large dose of ___ (beta adrenoceptor agonist), physical activity/physiological responses may not be able to surmount the antagonism e.g. climbing up stairs.

Isoprenaline

ADME refers to ___. What does ADME mean?

Pharmacokinetics | ADME is absorption, distribution, metabolism and excretion

Highly lipid soluble drugs may be sequestered in ___, resulting in slow distribution (because capacity is large and blood supply is poor).

Fat

Only ___ soluble drugs can cross the BBB.

Lipid

Cells act as a reservoir for the antimalarial drug ___ - it accumulates in liver cells which is useful to target the malaria parasite.

Quinicrine

The does "volume of distribution" mean?

Volume of body water in which a drug appears to be dissolved in after it has distributed throughout the body i.e. how widely the drug is distributed

Drugs may be eliminated by ___ (mainly by kidney) or ___ (mainly by liver).

Excretion - by kidney | Metabolism - by liver

In terms of excretion (by kidney), drugs bound to plasma protein are NOT ___.

Filtered

What does renal clearance mean?

The amount of blood from which drug is removed by the kidneys per time (i.e. L/min)

Drug metabolism increases ___ solubility to facilitate excretion.

Water

Phase ___ metabolism creates chemical functional groups on drugs. This often involves the ___ ___ enzymes.

Phase I metabolism | Cytochrome p450s

Phase ___ metabolism involves ___ of water soluble molecules to functional groups on drugs. Therefore, phase ___ metabolites with added functional groups may undergo phase ___ metabolism.

Phase II - conjugation of water soluble molecules to functional groups on drugs In phase I - addition of functional groups, so can undergo phase II after phase I

In anaemia, there is ___ oxygen delivery to tissues except if there is a compensatory increase in ___ ___.

Reduced oxygen delivery | Except if there is compensatory increase in cardiac output

What are the clinical signs of anaemia?

Pallor, lethargy, failure to thrive, hypoxia (e.g. dizziness), ischaemia, tachycardia (usually in acute blood loss c.f. chronic)

Anaemia may be classified as regenerative or aregenerative. In regenerative anaemia, ___ is depleted rapidly and therefore, O2 delivery and patient health can deteriorate rapidly.

Reticulocytes and polychromasia are signs of ___ production of RBCs, and jaundice, haptoglobins and LDH are signs of ___ destruction.

Increased | Increased

RBCs are replaced every ___ days, WBCs are replaced every ___-___ days and platelets are replaced every ___ days.

RBCs - 120 days WBCs - 3-5 days Plts - 10 days

In the first weeks of life, haemopoiesis occurs in the ___ ___.

Yolk sac

From 6 weeks to 7 months of life, haemopoiesis occurs in the ___ and ___. Therefore if there is blood diseases, these organs may be enlarged. From 7 months onwards, blood cells are produced in ___ ___.

Liver and spleen | Bone marrow

3 main haematinics - nutrients required for RBC production/development in bone marrow?

Iron Vitamin B12 Folate Vitamin B12 and folate are important for production of all cells, but esp. for rapidly proliferating cells and blood cells

What is Virchow's triad and what are the 3 parts of the triad?

Virchow's triad are the three main factors that contribute to thrombosis Blood flow - i.e. haemodynamics Blood composition - i.e. hypercoagulability Vessel wall i.e. endothelial dysfunction/damage

Carbon ___ binds 200x more tightly to haem than O2 - this is because it binds to haem at a straight angle, but O2 binds to haem at an angle of ___ degrees.

Monoxide | O2 binds haem at 120 degrees - easily unbound

Hb has high affinity for O2 when O2 saturation is ___ (e.g. in the ___). but has lower affinity for O2 when O2 saturation is ___ (e.g. in muscle). The affinity of Hb is represented by a ___ curve on a graph.

High affinity when O2 saturation is high e.g. in lungs Low affinity when O2 saturation is low e.g. in muscle - dissociates from Hb easily and transfers to Mb in muscle Sigmoidal curve

Myoglobin is a monomer therefore, does NOT exhibit ___ unlike Hb.

Cooperativity

Hb is composed of 2 ___ and 2 ___ subunits.

2 alpha and 2 beta

O2 is both a ligand and a homotropic (same ligand) ___ modulator of Hb. Therefore, binding of Hb at one site enhances binding of Hb at another site i.e. cooperativity.

Allosteric

___,___-___ is a heterotropic ___ modulator of Hb. Heterotropic means it is different from the normal ligand of Hb - O2.

2,3-bisphosphoglycerate | Allosteric

2,3-BPG is synthesised in ___ ___ ___ more than in other tissues.

Red blood cells

At ___ altitude, 2,3-BPG level increases. This allows more efficient unloading of O2 in tissues.

High

In RBCs stored before transfusion, there is depletion of ___, therefore there can be temporary but clinically significant impairment of O2 transport.

Depletion of 2,3-BPG

Foetal Hb (HbF) has ___ affinity for O2 than maternal/adult Hb (HbA).

Higher - takes O2 from mother

___-___ fibres come from the CNS and ___-___ fibres come from autonomic ganglia.

Pre-ganglionic from CNS | Post-ganglionic from autonomic ganglia

The autonomic nervous system includes ___ and ___ nervous systems, and is a ___ fibre system - using ___-___ and ___-___ fibres.

Sympathetic and parasympathetic nervous systems | 2 fibre system - uses pre-ganglionic and post-ganglionic fibres

The somatic nervous system is a ___ fibre system that innervates ___ muscle.

Single fibre system | Innervates skeletal muscle

Parasympathetic ___ are generally close to the organ that the post-ganglionic fibre innervates.

Ganglia

Sympathetic ganglia are found in the sympathetic ___ near the ___ ___.

Sympathetic chain near the spinal cord

The major PNS neurotransmitters include ___ and ___.

ACh and noradrenaline

The amino acid ___ is a precursor in the production of L-DOPA and dopamine and therefore ___ and ___.

Tyrosine | Noradrenaline and adrenaline

ACh is mainly inactivated by degradation by ___ ___ on the post-junctional membrane into choline and acetate. ___ is recycled.

Acetylcholine esterase | Choline

Noradrenaline is mainly inactivated by uptake by high-affinity uptake 1 on ___-___ neuron or low-affinity uptake 2 on ___-___ neuron into the synapse.

HA uptake 1 on pre-junctional neuron | LA uptake 2 on post-junctional neuron

Atropine and curare are ___ of ACh receptors.

Antagonists

___ inhibits exocytosis of vesicles with ACh so there is no release of ACh into the synapse.

Botox

Myasthenia gravis is an autoimmune disease in which there are antibodies to ___ ___ receptors on ___ muscle. Antibodies bind to the receptors and activate complement resulting in damage of the muscle membrane and ___ of the receptor.

Nicotinic cholinergic receptors on skeletal muscle | Internalisation of receptor

Basal release of ___ ___ regulates vascular tone.

Nitric oxide

Lipid mediators are derived from ___ acid. This has ___ carbons and ___ double bonds.

Arachidonic | 20 carbons, 4 double bonds (i.e. C20:4)

Arachidonic acid is bound to ___ in circulation, then uptaken to cells and ___ in membrane phospholipids.

Albumin | Esterified in membrane phospholipids

Increase in intracellular calcium activates ___ ___ resulting in the release of arachidonic acid.

Phospholipase A2

COX enzymes are expressed in ___ cells. COX-1 is ___ expressed for production of physiological prostaglandins, but COX-2 is ___ by inflammatory stimuli e.g. IL-1.

ALL cells COX-1 - constitutive COX-2 - inducible

Aspirin ___ or irreversibly binds to the serine active site of ___ enzymes.

Covalently | COX

Platelets in the GI circulation are exposed to ___ [aspirin] and because they lack a ___, they cannot re-synthesise ___ enzymes. But [aspirin] in systemic circulation is ___ and endothelial cells have a ___ so they can resynthesise ___. The ___/___ is increased so aspirin is cardioprotective.

High [aspirin] to platelets in GI circulation No nucleus in platelets - no resynthesis of COX enzymes Low [aspirin] in systemic circulation AND endothelial cells have nuclei SO they can resynthesise COX anyway PGI2/TXA2 ratio is increased because endothelium produces PGI2 and platelets produce TXA2 - TXA2 decreases but PGI2 is maintained!

Montelukast is a ___ receptor antagonist.

Leukotriene