Basic Cellular Flashcards
Sympathetic preganglionic neutrons originate where?
Lateral horn of segments T1-L2 of the spinal cord and exit via the ventral horn on their way to the paravertebral or prevertebral ganglia.
Parasympathetic preganglionic neutrons originate where?
The brainstem from which they run in the cranial nerves III, VII, IX and X and also from the second and third sacral segments of the spinal cord.
What do both sympathetic and parasympathetic preganglionic neurons release into the synapse?
Acetylcholine, which acts on cholinergic nicotinic receptors on the postganglionic fibre.
Sympathetic postganglionic neurons terminate in the effector organs where they release what?
The catecholamine noradrenaline (norepinephrine), which antics on alpha and beta adrenergic receptors which are linked via G-proteins to cellular effector mechanisms.
Parasympathetic postganglionic neurons release what?
Acetylcholine, which acts on cholinergic muscarinic receptors.
What effect does the sympathetic nervous system have on the urinary bladder?
Relaxes urinary bladder
What effect does the sympathetic nervous system have on the pupils?
Dilates pupils
What nervous system stimulates erection?
Parasympathetic nervous system
What nervous system stimulates both male and female orgasm?
Sympathetic nervous system
Action potentials are initiated in nerves by activation of what?
Ligand-gated Na+ channels by neurotransmitters
What is the mV of the negative resting membrane potential?
-70mV
What is the mV of the threshold potential required for an action potential to occur?
-55mV
What happens during depolarisation?
Voltage-gated Na+ channels open, causing further depolarisation and activating more voltage-gated Na+ channels and their is a sudden and massive sodium influx, driving the cell membrane potential to about +40mV
As the membrane potential becomes positive what happens to the voltage-gated Na+ channels?
They inactivate, preventing further sodium influx.
With voltage-gated Na+ channels inactivated, what causes repolarisation?
Potassium efflux
What is the resting membrane potential of a cardiac myocyte?
About -90mV
Myelinated fibres are insulated except at areas devoid of myelin called what?
Nodes of Ranvier
The depolarisation jumps from one node of Ranvier to another occurs in a process known as what?
Saltatory conduction
The arrival of an action potential at the nerve ending of the preganglionic neutron causes the opening of what?
Voltage-gated Ca2+ channels in the presynaptic membrane
In cholinergic synapses, after activation at the postsynaptic membrane, how are neurotransmitters removed from the synaptic cleft?
Cholinesterase rapidly breaks down acetylcholine into choline and acetate which are then recycled.
In adrenergic synapses, after activation at the postsynaptic membrane, how are neurotransmitters removed from the synaptic cleft?
Most noradrenaline is taken up by the nerve ending and recycled. Excess noradrenaline and sympathomimetic amines such as tyramine are metabolised in the neutron by mitochondrial monoamine oxidase (MAO)
Noradrenaline and other catecholamine in the circulation are metabolised sequentially by what?
Catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)
A negative feedback system comprises 3 components?
A detector
A comparator
An effector
About half of each cell is filled with a viscous, protein-rich fluid, called what?
Cytosol
What structure within the cell is responsible for the production of ribosomes?
Nucleolus
The nucleus contains most of the cell’s genetic material, organised as what?
Chromosomes
What does the mitochondria do?
- Production of chemical energy in the form of ATP by oxidative phosphorylation.
- Involved in Ca2+ homeostasis and signalling
- Contains small amount of maternal DNA
What is the role of the smooth endoplasmic reticulum?
Major site of lipid production and serves as a store for intracellular Ca2+
What is the role of the rough endoplasmic reticulum?
Has ribosomes bound to its outer surface, which are responsible for protein assembly and post-translational processing of proteins. This includes trimming amino acids to the right length, protein folding, addition of polysaccharide chains and identification of improperly folded proteins, which are tagged for subsequent destruction by lysosomes.
What is the role of the Golgi apparatus?
Packages proteins for delivery to specific intracellular destinations or into vesicles which can then be secreted from the cell for extracellular action.
What is the role of lysosomes?
Digestion and breakdown of unwanted and defective proteins, the recycling of raw materials and prevention of accumulation of waste
The Na+/K+ -ATPase antiporter pump uses primary active transport to move what?
3 Na+ ions out of the cell for every 2 K+ ions in, against their respective electrochemical gradients
What are the 3 steps of cellular respiration?
- Glycolysis
- The Krebs cycle
- The electron transfer system
The main respiratory substrate used by cells is what?
6-carbon glucose
When fats are used as the respiratory substrate, an excess of amount of what is produced?
Acetyl-CoA, which is converted into acetone and ketone bodies
Where does glycolysis take place?
In the cytoplasm
What is glycolysis?
Breakdown of 6-carbon glucose into two 3-carbon pyruvic acid (pyruvate) units
What is the energy net gain from glycolysis?
2 ATP
Where does the Krebs cycle take place?
Matrix of the mitochondrion
What happens in the Krebs cycle?
2-carbon acetyl CoA joins with 4-carbon compound to form a 6-carbon compound called citric acid. Citric acid (C6) is gradually converted back to the 4 carbon compound ready to start the cycle once more. The carbons removed are released as CO2. The hydrogens which are removed join with NAD to for NADH2.
Where does the electro transfer system take place, where most of the energy produced during respiration is made?
Inner mitochondrial membrane.
How many molecules of ATP are produced during aerobic respiration?
38
How many molecules of ATP are produced during anaerobic respiration?
2
In anaerobic respiration, what is the pyretic acid produced during glycolysis converted into?
Lactic acid
Haemopoiesis in the foetus occurs firstly where?
Yolk sac, and later in the liver and spleen
In normal childhood and adult life, haemopoiesis is restricted to where?
Bone marrow
All blood cells develop from what kind of cells?
Haemopoietic stem cells (HSCs)
Haemopoietic stem cells give rise to the lymphoid lineage in which a common lymphoid progenitor gives rise to what 3 cells?
B-cells, T-cells and natural killer (NK)cells
Haemopoietic stem cells give rise to the myeloid lineage in which a common myeloid progenitor gives rise to what 4 cells?
Erythrocytes, platelets, granulocytes and monocytes
Where does harm synthesis largely occur?
Mitochondria
How is haem formed?
Series of biochemical reactions commencing with the condensation of glycine and succinylcholine coenzyme A under the action of the key rate-limiting enzyme delta-aminolevulinic acid (ALA) synthase; ultimately protoporphyrin combines with iron in the ferrous (Fe2+) state to form haem.
How are globin chains created?
Synthesised by ribosomes in the cytosol.
Red blood cells are destroyed by what cell in the liver and spleen after 120 days?
Macrophages
What are the 3 types of haemoglobin in normal adult blood?
- HbA - normal adult haemoglobin makes up about 96-98% of total adult haemoglobin, consists of 2 alpha and 2 beta global changes.
- HbA2 - normal variant, 1.5-3.5% of normal adult haemoglobin, consists of 2 alpha and 2 delta global chains.
- HbF - foetal haemoglobin, 0.5-0.8% of adult haemoglobin, consists of 2 alpha and 2 gamma globulin chains.
Does foetal haemoglobin have a higher of lower affinity for oxygen than adult haemoglobin?
Higher
Where is erythropoietin produced?
90% is produced in the peritubular complex of the kidney and 10% in the liver and other organs
Erythropoetin secretion is stimulated by what?
Reduced O2 supply to the kidney receptor (i.e. tissue hypoxia and reduced haemoglobin concentration - anaemia)
Increased pathological secretion of erythropoietin may occur in what conditions?
Polycystic kidney disease and renal cell carcinoma
What conditions may cause a decreased secretion of erythropoietin?
Chronic kidney disease and polycythaemia
Do reticulocytes or erythrocytes stain blue with cresyl blue staining and why?
Reticulocytes - due to residual RNA
What is reticulocyte count a measure of?
New red cell production
What causes a raised reticulocyte count?
Haemorrhage or haemolysis when extra red cell production is needed
What percentage of circulating red cells are reticulocytes?
1-2%
What are causes of a low reticulocyte count (marrow incapable of normal red cell production)?
- General bone marrow failure (malignant infiltration, aplastic anaemia).
- Impaired red blood production (deficiency of iron, vitamin B12 or folate).
- Lack of erythropoietin stimulus (chronic kidney disease).
- Chronic systemic disease
An isolated reticulocytosis without anaemia is relatively common as a direct toxic effect of what?
Alcohol
Coagulation is initiated after vascular injury by the interaction between which 2 factors?
Membrane bound tissue factor (TF, factor III) and plasma factor VII
In the coagulation cascade, the factor VIIa-tissue factor (extrinsic factor Xase) complex activates which 2 factors?
Factor IX and factor X
In the coagulation cascade, factor Xa, in the absence of its cofactor, forms small amounts of what from prothrombin?
Thrombin
In the coagulation cascade, amplification take place where?
On the surface of platelets
The small amount of thrombin generated during the initiation phase activates nearby platelets and also which cofactor on their surface?
Cofactor V
Which cofactor is normally bound to plasma von Willebrand factor (VWF)?
Cofactor VIII
What cleaves factor VIII from VWF and activates it?
Thrombin
The intrinsic Xase, formed by IXa and VIIIa on phospholipid surface activates sufficient Xa in the presence of which electrolyte?
Ca2+
Thrombin hydrolyses fibrinogen to form what
Fibrin monomers
Where are platelets produced?
In the bone marrow by fragmentation of the cytoplasm of megakaryocytic, derived from the common myeloid progenitor cell.
The time interval diffraction of the human stem cell to the production of platelets averages how long?
10 days
What is the major regulator of platelet formation?
Thrombopoietin
Where is 95% of thrombopoietin produced?
Liver
What is the normal platelet lifespan?
10 days
Under normal circumstances, how much of the marrow output of platelets may be trapped at any one time in the normal spleen?
About one-third
Which glycoproteins are important in the attachment of platelets to von Willebrand factor (VWF), and hence to vascular subendothelium?
Glycoproteins Ib and IIb/IIIa
What are the 3 types of storage granule platelets contain?
- Dense granules containing ADP, ATP, serotonin and calcium.
- Alpha granules containing clotting factors, von Willebrand factor (VWF), platelet-derived growth factor (PDGF) and other proteins.
- Lysosomes containing hydrolytic enzymes
The primary function of platelets is the formation of a platelet plug during the primary haemostatic response to vascular injury via what 3 mechanisms?
Adhesion, aggregation and activation
What is the role of Thromboxane A2 (TXA2)?
Important in secondary amplification of platelet activation to form a stable platelet aggregate. TXA2 lowers platelet cAMP levels and initiates the platelet release reaction. It also has a powerful vasoconstrictive activity.
After platelet aggregation and release, the exposed membrane phospholipid is available for which 2 reactions in the coagulation cascade?
- The first involves factors IXa, VIIIa and X in the formation of factor Xa.
- The second results in the formation of thrombin from the interactions of factors Xa, Va and prothrombin.
PDGF found in the alpha granules of platelets simulates what?
Stimulates vascular smooth muscle cells to multiply and thus may hasten vascular healing following injury
Name 2 substances which inhibit platelet function?
- Prostacyclin (PGI2), which is synthesised by endothelial cells, has the opposing effects of TXA2; it is a potent inhibitor of platelet adhesion and aggregation on normal vascular endothelium (and a potent vasodilator).
- Nitric oxide is constitutively released from endothelial cells and also from macrophages and platelets; it inhibits platelet activation and promotes vasodilation.
The thrombin generated by the coagulation cascade converts soluble plasma fibrinogen into fibrin monomers, potentiates platelet aggregation and secretion and also activates 2 factors and 2 cofactors - name them?
Factor XI and XIII
Cofactors V and VIII
Which 3 factors do tissue factor pathway inhibitor (TFPI) inhibit?
Xa, VIIa and tissue factor
Protein C and protein S inhibit which 2 coagulation cofactors?
V and VIII
At the periphery of a damaged tissue area, undamaged endothelium produces which 2 substances which impede platelet adhesion and activation?
Prostacyclin and nitric oxide
D-dimer is a measurement of what?
Fibrin degradation products (FDPs)
Plasmin is important for Fibrinolysis and is capable of digesting fibrinogen, fibrin, factors V, VIII and many other proteins. Plasmin itself is inactivated by what?
Alpha2-antiplasmin
Pressure across the wall of a flexible tube (transmural pressure) tends to extend it, and increases wall tension. This can be described by Laplace’s Law, what is the formula for this?
Pt = (Tw)/r
Where,
Pt = Transmural pressure
T = Wall tension
w = Wall thickness
r = Radius
Flow through a tube is dependant on the pressure differences across the ends of the tube (P1-P2) and the resistance to flow provided by the tube (R). What is the formula for Darcy’s law to determine flow?
Darcy’s Law states that, Flow = (P1-P2)/R
Resistance is due to frictional forces and is determined by the length of the tube (L), the radius of the tube (r) and the viscosity of the fluid flowing down that tube (V). What is the formula as states by Poiseulille’s law?
Poiseuille’s Law states: R = (8VL)/(πr
Resistance is due to frictional forces and is determined by the length of the tube (L), the radius of the tube (r) and the viscosity of the fluid flowing down that tube (V). What is the formula as states by Poiseulille’s law?
Poiseuille’s Law states: R = (8VL)/(πr
Resistance is due to frictional forces and is determined by the length of the tube (L), the radius of the tube (r) and the viscosity of the fluid flowing down that tube (V). What is the formula as states by Poiseulille’s law?
Poiseuille’s Law states: R = (8VL)/(πr
Resistance is due to frictional forces and is determined by the length of the tube (L), the radius of the tube (r) and the viscosity of the fluid flowing down that tube (V). What is the formula as states by Poiseulille’s law?
Poiseuille’s Law states: R = (8VL)/(πr
Resistance is due to frictional forces and is determined by the length of the tube (L), the radius of the tube (r) and the viscosity of the fluid flowing down that tube (V). What is the formula as states by Poiseulille’s law?
Poiseuille’s Law states: R = (8VL)/(πr
Resistance is due to frictional forces and is determined by the length of the tube (L), the radius of the tube (r) and the viscosity of the fluid flowing down that tube (V). What is the formula as states by Poiseulille’s law?
Poiseuille’s Law states: R = (8VL)/(πr⁴)
The rate of diffusion in a solution is described by Fick’s law, which states what?
Js = -DA (△C/△x)
where:
Js = Amount of substance transferred per unit of time
△C = Difference in concentration
△x = Difference in distance
A = Surface area over which diffusion occurs
D = Diffusion coefficient
Diffusion across a membrane is affected by the permeability (p) of the membrane. The permeability is related to the membrane thickness and composition, and the diffusion coefficient of the substance. What is Fick’s equation for diffusion across a membrane?
Js = -pA△C
where:
Js = Amount of substance transferred per unit of time
△C = Difference in concentration across the membrane
A = Membrane area over which diffusion occurs
p = Membrane permeability
An average 70kg male contains about 40 litres of water in total. How is this distributed?
Intracellular fluid - 27L (around two 3rds)
Extracellular fluid - 13L (Intravascular fluid - 3.5L, interstitial fluid -9.5L)
What is the main difference between interstitial and intravascular fluid?
Intravascular fluid contains more protein
What is the principle extracellular cation?
Sodium (Na+): approximately 140mmol/L is extracellular and 10mmol/L intracellular
What is the principle intracellular cation?
Potassium (K+): approximately 4mmol/L is extracellular and 140mmol/L intracellular
Is magnesium (Mg2+) a predominately intracellular or extracellular ion?
Intracellular
Intracellularly, what are the 2 main anions?
Protein and phosphate
Extracellularly, what are the 2 main anions?
Chloride and bicarbonate
Negatively charged intracellular proteins that cannot cross the plasma membrane of cells, effectively repel Cl- ions, which can diffuse freely across the plasma membrane, forcing them out of the cell. The eleictrical force driving the Cl- ions out is balanced by the chemical gradient driving them back in, what is this known as?
The Gibbs-Donnan Equilibrium
What is osmolality?
The concentration of a solution expressed as the total number of solute particles per kilogram weight of solvent
What is normal serum osmolality?
275-295 mosmol/kg
What is the equation for calculating serum osmolality?
2(Na+) + 2 (K+) + Glucose + Urea
What is the osmolal gap? And what is a normal osmolal gap?
The apparent difference between the measured and the calculated osmolality. Normal is <10.
Osmolal gaps of >10 are considered abnormal and represent the presence of an osmotically active substance in the blood. What substances can cause a raised osmolal gap?
Toxic alcohols (e.g. ethanol, methanol or ethylene glycol ingestion)
Sugars (e.g. mannitol, sorbitol)
Lorazepam infusions (which contain propylene glycol)
What is osmolarity?
The concentration of a solution expressed as the total number of solute particles per litre of solution.
For any given solution is osmolarity always slightly less or slightly more than the osmolality?
Always slightly less
What is the name of the connective tissue surrounding the whole muscle?
Epimysium
What is the name of the connective tissue that surrounds each muscle fibre?
Endomysium
Muscle fibres are grouped together to form fascicles. What is the name of connective tissue that surrounds each fascicle?
Perimysium
What is the functional unit of muscle called?
Sarcomere
In sliding filament theory, the thick filament is composed predominantly of myosin. Each molecule is club-shaped, with a thin tail, comprising 2 cold peptide chains and a head had up of what?
2 heavy peptide chains and four light peptide chains
The contraction of muscle is triggered by the release of what from the sarcoplasmic reticulum, where it is stored bound to calsequestrin?
Ca2+
Muscle contraction occurs when the concentration of intracellular Ca2+ rises. An action potential travels down tube-shaped invaginations of the sarcolemma called what?
T-tubules
Each muscle fibre is divided at regular intervals along its length into sarcomeres, separated by what?
Z-lines
In sarcomeres, what is the name of the zone of thin actin filament that is not superimposed by thick myosin filaments?
The I-band
In sarcomeres, what is the name of the band which extends along the whole length of the myosin filament?
The A-band
In sarcomeres, what is the name of the zone of thick myosin filament that is not superimposed by thin actin filaments?
The H-zone
In sarcomeres, the M-line is a disc of filaments in the middle of the H-zone that holds the myosin filament in position so that each one is surrounded by how my actin filaments?
6
In motor units, what is spatial summation?
The recruitment of additional motor units to generate more force
In motor units, what is temporal summation?
Increasing the firing rate of motor units
For most motor units, what is the firing rate for a steady contraction?
Between 5 and 8 Hz
In muscles, what is isometric contraction?
When the two ends of the muscle are help at a fixed distance apart (e.g. holding a weight with an outstretched hand)
Explain the 2 types of isotonic contraction in muscles?
- Concentric movements - muscle shorts as muscle fibres contract
- Eccentric movements - muscle lengthens in a controlled manner, due to the resistance being greater that the force the muscle is producing
The neurons that innervate skeletal muscles are called what?
Alpha-motor neurons
In skeletal muscle, the motor neurone axon terminal has a large number of vesicles containing what neurotransmitter
Acetylcholine (ACh)
In skeletal muscle, what happens when acetylcholine diffuses across the synaptic cleft between the nerve and the muscle cells, and stimulate a large number of cholinergic nicotinic receptors on the post-junctional membrane?
Ion channel opens and allows the influx of small cations, mainly Na+. This movement of positively charged ions generates an end plate potential (EPP) that is above threshold for triggering a self-propagating action potential in the muscle fibre
