1 Flashcards
(287 cards)
1
Q
What is physiology?
A
The science of the functions of living organisms and their parts
2
Q
What are the 4 essential components for maintaining a steady state?
A
- Receptors; can sense when vital parameters change
- Control centre; compares input against set point
- Output; signal from control centre to effector
- Effector; enables change to return to steady state
3
Q
What is redundancy?
A
When more than one homeostatic feedback loop is in place so if one system fails, steady state is resumed
4
Q
What is a mediator?
A
- Chemical, peptide or protein that conveys information from one cell to another.
- When in response to a stimulus, a mediator is released and produces a particular biological response.
5
Q
List the criteria which establish a substance as a mediator
A
- Released from cells in sufficient amounts to produce biological action within appropriate time frame.
- Application of authentic sample of mediator produces original biological effect.
- If we interfere with synthesis release or action then we should be able to stop biological response.
6
Q
Describe the synthesis of small molecule mediators
A
- Synthesis is regulated by specific enzymes.
- Peptide synthesis is regulated by transcription, after transcription, translation. It will go to the Golgi body and either be sent out of cell through constitutive or regulated secretory pathway. Product is released when stimulated.
- Mediators produces by cell depends on enzymes and genes.
- Cells can produce more than one type of mediator.
7
Q
What are the two types of chemical mediators?
A
- Mediators which are pre-formed and stored in vesicles from which they’re released by exocytosis allowing rapid communication.
- Mediators produced on demand which takes longer.
8
Q
How are neurotransmitters stored?
A
In ‘packages’ which release a quantal amount of neurotransmitter.
9
Q
What is a drug?
A
A chemical substance of known structure, other than a nutrient or essential dietary ingredient, which when administered to a living organism produces a biological effect.
10
Q
Describe the steps in chemical transmission that are targeted by drugs
A
- Drugs can interfere with transporters
- Drugs can target ion channels involved in neurotransmission
- Drugs can target receptors in neurotransmission
11
Q
What are the 4 classes of proteins commonly targeted by drugs?
A
- Enzymes
- Transporters
- Ion channels
- Receptors
12
Q
What are receptors?
A
Proteins that bind chemical mediators e.g. hormones, neurotransmitters, inflammatory mediators.
13
Q
What is the function of receptors?
A
The regulation of cellular processes:
- Chemical recognition and binding
- Intracellular signal generation
14
Q
What are the 4 classes of receptor targeted by therapeutic drugs?
A
- Ligand gated ion channels
- G protein couples receptors
- Kinase linked receptors
- Nuclear receptors
15
Q
What are the definitions of; agonist, antagonist, ligand?
A
Agonist- Drug or chemical that binds to receptor producing a response in the cell.
Antagonist- Drugs that prevent or inhibit the response of an agonist. Put onto cells in isolation they have no effect.
-Ligand- Any molecule that binds to receptor. Can be an agonist or antagonist.
16
Q
What are the varying speeds of signal transduction?
A
- Milliseconds; ligand gated ion channels as proteins just need to shift to open channels and ions diffuse down the gradient.
- Seconds; G-protein coupled receptors. Agonist bound receptor activates G-proteins which control the function of other proteins.
- Hours; Kinase linked receptors and nuclear receptors which both regulate gene transcription and therefore protein synthesis.
17
Q
Describe the structure and action of ligand gated ion channels
A
- Composed of 3-4 subunits.
- Each subunit has 2-4 transmembrane spanning domains.
- Complex arrangement forms central aqueous pore.
- Agonist binding leads to the opening of the channel.
- Channel closes due to drop in concentration of agonist or because receptor enters desensitised state.
18
Q
What does the activation of ionotropic receptors by excitatory neurotransmitters lead to?
A
- Membrane depolarisation
2. Action potential firing
19
Q
What does the activation of ionotropic receptors in inhibitory neurotransmitters lead to?
A
- Inhibits membrane depolarisation
- Reduces action potential firing
20
Q
What are the protein subunits and the structures?
A
- Cys-loop type; 4 transmembrane domains, cystine loops. Pentameric assembly.
- Ionotropic glutamate type; 3 transmembrane domains, p-loop facing ion channel. Tetameric assembly.
- P2X type; ATP gated channels. 2 transmembrane domains. Trimeric assembly.
- Calcium release type; 6 domains, tetrameric assembly.
21
Q
Describe the structure of G-protein coupled receptors
A
- Formed from a single protein
- Receptor protein spans membrane 7 times
- G-protein made from 3 proteins coming together (heterotrimeric)
22
Q
Describe the signal transduction mechanism in G protein coupled receptors
A
Neurotransmitter binds to receptor, stabilises it in particular structure which is highly attractive to heterotrimeric G-proteins that will lead to activation.
- G-protein in turn controls activity of downstream effector molecules e.g ion channels/ enzymes involves in production of 2nd messengers.
- Same G-protein can be used for many different receptors.
23
Q
Describe the process of switching ON heterotrimeric G-proteins
A
- Inactive G protein- Alpha subunit can be separate from beta gamma subunit.
- Alpha subunit contains binding site for nucleotide.
- GDP associated with alpha subunit then has high. affinity for beta gamma subunit forming a complex.
- When agonist molecule binds it leads to a structural rearrangement and attraction to the alpha subunit.
- Change in alpha subunit structure lowers GDP affinity and GTP affinity increases.
- G protein is active.
24
Q
What is PKA? How is it regulated by cAMP?
A
- Protein kinase A
- PKA regulated by phosphorylation of target proteins which in turn regulated their functions
25
What happens when phospholipase C is activated by GPCR's?
- Generation of 2nd messengers IP3 and DAG
- Increased intracellular Ca2+
- Activation of protein kinase C
- Recognises and breaks down certain phospholipids in plasma membrane
26
Describe the neuronal organisation of the ANS
- Preganglionic neurons are always short and cholinergic
- Postganglionic neurons have nicotinic receptors for ACh and are long and adrenergic
- Target tissues express alpha and beta adrenergic receptors for norepinephrine.
27
Describe the effects of sympathetic stimulation
- Eyes dilate
- Heart rate and contractility increase
- Blood vessels dilate towards skeletal muscles and constrict towards the digestive system
- Increased expansion of lungs. Dilation of smooth muscles in trachea and bronchioles
- Increased breakdown and release of glucose in liver
28
Describe the effects of parasympathetic stimulation
- Eyes constrict
- Heart rate decreases
- Blood flow to GI tract increases. Release of bile and enzymes increases.
- Bladder wall contracts
29
What parts of the body are innervated by sympathetic nervous system only?
- Sweat glands
- Hair follicles
- Blood vessel smooth muscle
- Adrenal medulla
30
Where are chromatin cells located? How do they work?
- Adrenal medulla
- Functions similar to postganglionic neurons but release mainly epinephrine
- Traget alpha and beta adrenergic receptors
- Allows diffuse sympathetic activity
31
Describe neuronal organisation of parasympathetic NS
- Long cholinergic preganglionic neurons from brainstem and sacral spinal cord
- Short cholinergic postganglionic neurons
- Target tissue expresses muscarinic ACh receptors
32
What are the essential components of the ANS in the CNS?
Spinal cord- mediates autonomic reflexes, recieves sensory afferents and brain stem outputs.
Brainstem nuclei- mediate autonomic reflexes
Hypothalamus- integration and coordination of behavioural processes
Forebrain and visceral inputs control cortical function
33
Another name for adrenaline
Epinephrine
34
What blocks muscarinic ACh receptors?
Atropine
35
How do M1, M3 and M5 receptors work?
- Gq protein coupled receptors
- Increase in phospholipase C
- Increase in IP3 and intracellular Ca2+
36
How do M2 and M4 receptors work?
- Gi protein coupled receptors
- Decrease in adenylyl cyclase so decrease in cAMP
- Increase in GIRK
- Decrease in voltage gated Ca2+ channels
37
Where in the body are M1 receptors found?
- Autonomic ganglia
- Gastric oxyntic glands
- Lacrimal and salivary glands
- Cerebral cortex
38
Where are M2 receptors found in the body?
- Atria of the heart
| - Widely distributed in the CNS
39
Where are M3 receptors found in the body?
```
Exocrine glands
Smooth muscle
GI tract
Eyes
Airways
Bladder
Endothelium of blood vessels
```
40
Where are M4 receptors found?
CNS
41
Where are M5 receptors found?
Substantia nigra
Salivary glands
Iris and ciliary muscles
42
What does M2 activation cause?
Cardiac slowing
Decreased force of contraction in atria
Inhibition of atrioventricular conduction
43
What is the effect of muscarine poisoning?
Decrease in blood pressure. Production of nitrous oxide leads to vasodilation.
- Increased saliva, tear flow, sweating and abdominal pain.
- Can lead to cardiac failure as heart rate slows.
44
What can pilocarpine be used to treat?
Eye drops used to treat glaucoma by reducing pressure in eye.
45
What is atropine and what are its effects?
- Atropine is a non selective muscarinic antagonist
| - Leads to inhibition of secretion from glands, relaxation of smooth muscle and relaxation of urinary tract
46
What are examples of muscarinic antagonists and what do they treat?
- Pirenzepine is used to treat peptic ulcers at level of M1 receptors regulating acid secretion into gut.
- Darifenacin is M3 selective and used in cases of overactive bladder.
47
What are cholinomimetic drugs? How do they do this?
Drugs that act indirectly to enhance cholinergic transmission.
-They inhibit cholinesterase and mimic the effects of activation of cholinergic signalling pathways.
48
Where are noradrenergic receptors found?
Tissues responding to postganglionic sympathetic neurons.
49
What are some clinical uses of adrenoreceptor agonists?
Adrenaline- Cardiac arrest and anaphylaxis
| B2 selective- ephedrine used for nasal decongestants, salbutamol used for bronchial dilation.
50
What are amphetamines?
- Indirectly acting sympathomimetic drugs
- Structurally related to noradrenaline, don't act directly on receptors but increase release of endogenous noradrenaline
51
What are the clinical uses of adrenoreceptor antagonists?
Prazosin for hypertension (Alpha 1 selective)
Carvedilol for heart failure (alpha and beta)
Propanol for anxiety (beta 1 and 2)
52
What does the endocrine system regulate?
- Growth and development
- Reproduction
- Blood pressure
- Concentrations of ions in the blood
- Behaviour e.g. hunger and mood
53
What are the basic principles of the endocrine system?
- Chemicals known as hormones are secreted from endocrine tissues or glands into extracellular fluid
- Transported by blood to distant target tissues
- Receptors can be found on cell surface, in cytosol or in nucleus
54
What are the 7 classic endocrine glands?
- Pituitary (anterior and posterior)
- Thyroid
- Parathyroids
- Adrenals (cortex and medulla)
- Ovaries
- Testes
- Endocrine pancreas
55
What are other endocrine tissues which are not the 7 classic endocrine glands?
- Hypothalamus
- Kidneys
- GI tract
- Heart
- Liver
- Adipose tissue
56
What is the function of the thyroid gland?
It is essential for development, growth and metabolism
57
Describe the process of secretion from the thyroid gland
- Numerous follicles in the thyroid gland which are surrounded by follicular cells with colloid in centre.
- Iodine is required to create a pre-hormone which is secreted by follicular cells into colloid where it's stored extracellularly until thyroid hormones are needed.
- When needed, pre hormone is taken back up into follicular cells and converted into thyroid hormones T3 and T4.
- T3 and T4 exit cells by facilitated diffusion and enter interstitial fluid and into bloodstream and target cells.
- Enter cells via facilitated transport and bind to nuclear receptors, meaning they can regulate transcription of proteins.
58
What is the function of the parathyroid gland and how does it do this?
- Aims to increase plasma calcium levels which act as feedback loop in chief cells. Prevents parathyroid hormone granules being released. Also regulates phosphate levels.
- Chief cells release parathyroid hormone via exocytosis into interstitial fluid.
- Peptide hormone released from secretory granules.
- Moves around in blood and moved to targets:
- Intestines where it increases calcium absorption.
- Kidneys where it increases tubule calcium reabsorption.
- Increases amount of bone calcium reabsorption.
59
What are the 3 things released by the adrenal cortex?
- Mineralocorticoids e.g. aldosterone. Capable of regulating amount of sodium in the bloodstream.
- Glucocorticoids e.g. cortisol. Capable of regulating glucose. Cortisol is released and can increase the amount of blood plasma glucose. Released in stressful situations when more energy is needed.
- Androgens.
60
What is released from the adrenal medulla?
- Chromaffin cells which release adrenaline and noradrenaline.
- Blood enters artery and works its way down through blood vessels towards vein.
- Cortisol is released from cells, travelling in blood vessels to reach adrenal medulla. This can stimulate chromaffin cells to release adrenaline.
61
What is the endocrine function of the ovaries?
- Developing follicles which produce oestrogen and progesterone.
- Oestrogen stimulates cellular proliferation of the lining of the uterus.
- Progesterone stimulates secretions and maturation of the tissues.
62
What is the endocrine function of the testes?
- Leydig cells produce testosterone which stimulates protein synthesis.
- Plasma testosterone increases at puberty and reaches a peak at adulthood. Levels then decrease with old age.
63
What are the 2 types of cell in the islets of Langerhans and what do they release?
Alpha cells- produce glucagon. Initiate release of glucose.
| Beta cells- release insulin which controls blood glucose levels from getting too high leading to glucose storage.
64
What is the adenohypophysis? Describe its action
- Anterior lobe of pituitary which develops from upward projection of pharynx.
- Receives hormones from hypothalamus.
- Small diameter neurons with shirt axons which release hormones which travel down through portal veins, distributing to troph cells.
- Troph cells are stimulated to release further hormones which enter bloodstream.
65
What is the neurohypophysis? Describe its action
- Posterior lobe of pituitary
- Develops from downward projection of brain
- Large diameter neurons in hypothalamus send axons down into posterior pituitary
- Release hormones directly into bloodstream
66
What are the major pituitary hormones and what are their roles?
ADH- regulates water balance
Oxytocin- involved in lactation. Hormone involved in forming bonds with people
Tropic hormones- hormones which cause the release of more hormones:
Thyroid stimulating- stimulates thyroid gland to release thyroid hormones.
-FSH and LH released by anterior pituitary acting on testes and ovaries.
67
From what does epithelia develop from?
All 3 germ layers:
- Endoderm; GI lining
- Mesoderm; Lining of CV system
- Ectoderm; Epidermis
68
What are the functions of epithelial tissue?
- Protection, for example in the skin
- Diffusion, for example in the lungs
- Secretion, for example in the glands
- Absorption, for example in small intestines
69
What is the basement membrane? Describe its structure
- A vital component of all epithelia, all epithelial cells are connected together on basal surface to basement membrane which adds mechanical support and provides nutrients for growth (cells rely on basement membrane for nutrients as they are avascular)
- The basement membrane consists of 2 parts:
1. Basal lamina which provides support and is secreted by epithelial cells.
2. Reticular lamina which anchors cells to extracellular matrix and is secreted by fibroblasts
70
Why is cell replacement in epithelia important?
- Some of the external environments can be hostile meaning cells will often die.
- Tissue homeostasis is maintained through continual replacement of cells through homeostasis.
71
Describe the structure and function of simple squamous epithelium
Appearance of thin scales
Facilitates rapid passage of molecules
Nuclei are flat and horizontal, mirroring the shape of the cells
Present where rapid passage of molecules is required, for example in the lungs
72
Describe the structure and function of simple cuboidal epithelium
Nucleus is in the centre of the box like presentation
Involved in secretion and absorption of molecules which require active transport
Present in lining of kidney tubules and ducts of glands
73
Describe the structure and function of simple columnar epithelium
Tall elongated cuboidal cells with the nucleus at the bottom of the cell
Involved in active transport during absorption or secretion of molecules
Can be ciliated and con-ciliated
Present in GI tract and Fallopian tubes
74
Describe the structure and function of pseudo stratified columnar epithelium
Irregular arrangement of cells and nuclei
All cells are in touch with the basement membrane, some cells don't reach the apical surface
Found in the respiratory system
75
Describe the structure and function of stratified squamous epithelium
Most common type of epithelia in human body
Cells on apical surface are squamous, could be dead and contain large amounts of keratin
Basal cells are more cuboidal
Found in areas of high abrasion e.g. skin and oesophagus
76
Describe the structure and function of stratified cuboidal epithelia
Found in glands and ducts
Acts as protection
Cuboidal cells arranged in layers
77
Describe the structure of stratified columnar epithelia
Rare and found in conjunctiva, pharynx, embryos
Allows tissue to stretch and contract
Contains goblet cells which secrete liquid in order to lubricate e.g. in eyelids
78
Describe the structure and function of transitional epithelia
Relaxed and distended presentations allow contraction e.g. in bladder
When relaxed, cells have round shape and when distended, change shape without being damaged
79
Describe the structure and function of glandular epithelium
Gland made up of one or more cell types that are modified to secrete a chemical
Can be exocrine- ducts open to external environment
Exocrine- ductless and secrete into surrounding tissues
80
What is the integumentary system?
The skin (integument) and its accessory organs; hair, nails, cutaneous glands
81
What is the dermis? Describe its structure
Connective tissue beneath the epidermis
Mainly collagen with elastic and reticular fibres
2 zones with unclear boundaries:
1. Papillary layer; thin region of loose connective tissue allowing mobility of leukocytes, mast and macrophage cells
2. Reticular layer, thick layer of dense irregular connective tissue. Often has adipocyte clusters
-Accessory organs such as hair, nails and oil and sweat glands are from dermis
-Rich layer of blood and lymphatic vessels
82
Why is the dermal-epidermal boundary so strong?
Due to wavy boundary of finger like projections which interlock to create large surface area and strong boundary
Dermal papillae come up from dermis and epidermal ridges come down from epidermis
83
What are the 5 layers of the epidermis?
```
Stratum basale
Stratum spinosum
Stratum granulosum
Stratum lucidium
Stratum corneum
```
84
What is the role of stem cells in the epidermis?
They give rise to keratinocytes. Cells in contact with the basement membrane maintain the ability to replicate.
85
What is the role of keratinocytes in the epidermis?
Keratinocytes- Have the ability to synthesise keratin.
86
What is the role of langerhans cells in the epidermis?
Dendritic cells, macrophages that originate in bone marrow and migrate to epidermis guarding against pathogens and toxins.
87
What is the role of Merkel cells in the epidermis?
Tactile cells which are touch receptors associated with nerve fibres.
88
Describe the structure of the stratum basale and the cells within it
Consists of undifferentiated mitotically active keratinocytes attached to the epidermal basement membrane, they generate cells for other layers.
Cells migrate upwards.
Single layer of cuboidal cells and keratinocytes resting on basement membrane. Melanocytes are scattered among other cells.
Tactile and Merkel cells connect to nerves to give a sense of touch.
89
What are the role of melanocytes and what are the pigments within them?
```
Synthesise the pigment of melanin.
Melanin is UV absorbent and protects the skin from UV damage.
Provides pigmentation through:
-Pheomelanin (red soluble pigment)
-Eumelanin (brown insoluble pigment)
```
90
Describe the structure of the stratum spinosum
Several layers of keratinocytes.
Thickest layer in thin skin.
Deepest cells are mitotic and as they're pushed up they cease to divide.
Produce keratin filaments, causing cells to flatten.
Keratinocytes are strongly linked by desmosomes.
Tight junctions between cells ensure water retention of skin.
91
Describe the structure of the stratum granulosum
3-5 layers of flat keratinocytes.
Post mitotic cells.
Contain dark staining keratohyalin granules which bind to cytoskeleton and are converted to keratin.
Cells undergo apoptosis.
Produce glycolipid filled vesicles which spread over cell surface forming waterproof barrier between stratum spinosum.
92
Describe the structure of the stratum lucidum
```
Only exists in thick skin.
Thin translucent zone.
Densely packed keratinocytes but with no nuclei or organelles.
Protects against damage.
Indistinct cell boundaries.
```
93
Describe the structure of the stratum corneum
Outermost later in contact with the environment.
15-30 layers thick.
Terminally differentiated dead keratinocytes which continually flake off.
Compromised of several layers of flattened corneocytes.
Stratum disjunction is lost to the environment.
94
Describe the structure of nails as an accessory structure
Derivatives of stratum corneum.
Composed of dead scaly cells and densely packed with hard keratin fibres.
Their appearance cam indicate health issues e.g. iron deficiency- flat or concave.
95
Describe the structure and different types of hair as an accessory structure
Slender filament of keratinised (dead) cells from follicles.
Found almost everywhere with different densities.
Lanugo- fine hair in foetuses.
Vellus- fine unpigmented hair.
Terminal hair- longer coarse pigmented hair e.g eyebrows.
96
What are the 5 types of glands in skin and what do they secrete?
Merocrine sweat glands- Provide watery perspiration to skin.
Apocrine sweat glands- Ducts lead to follicles. 'Scent glands' respond to stress and sexual stimulation.
Sebaceous glands- Oily sebum lubricated skin and hair.
Ceruminous glands- E.g. earwax
Mammary glands- In females for milk.
97
What is the barrier function of skin and how is it achieved?
- Prevents water loss, physical injury and infection by microbes.
- Skin is host to a large and complex microflora or over 1000 species, many are harmless but some are opportunistic pathogens.
- Physical barrier, cross-linked keratin layer upon scaffold of keratinocytes. Only fails in areas of cuts and burns.
- Biochemical barrier; slightly acidic and bactericidal agents such as saturated and unsaturated fatty acids which inhibit growth of bacteria.
98
Describe the process of temperature regulation
- Thermoreceptors in the epidermis.
- Countercurrent heat exchange between arterial and venous blood flow in extremities.
- Hypothalamus regulates via ANS.
- Sweat so heat leaves body via evaporation when warm.
- Piloerection by piloreceptor muscles to make hairs stand up and trap heat when cold.
99
What are skeletal muscles responsible for?
- Voluntary movement of bones that underpin locomotion.
- Control of inspiration by contraction of diaphragm.
- Skeletal muscle pump helps with venous return to heart.
100
What creates the striated appearance of skeletal muscles (what makes up the H, I and A band)?
H band- just myosin fibres
I band- just actin fibres
A band- myosin and actin overlap in this area.
101
Describe the process of initiating skeletal muscle contraction
- Requires nervous stimulation
- Motor neuron's axon forms neuromuscular junction on muscle fibre
- Action potential comes down axon, reaching neuromuscular junction, stimulating release of ACh into synaptic cleft
- ACh binds to nicotinic ACh receptirs, initiates action potential in membrane of muscle fibre, passing down muscle fibre leading to contraction
- Wave of depolarisation passes along sarcolemma through T tubule
- Depolarisation triggers increase in intracellular Ca2+
102
Describe the process of muscle contraction
ATP dependant
Actin and myosin are bound together and no ATP currently involved
ATP binds to myosin head, causing it to dissociate from actin
ATP hydrolysed to ADP and phosphate, causing conformational change. Myosin head extends out
Myosin head then able to interact with actin molecules further down chain. Once bound to actin, phosphate is released
Strong interaction between actin and myosin head
Conformational change in myosin head into upright position, pulling actin filament
ADP released and process repeats
103
What is fused tetanus?
Action potential causes muscle to contract and relax (twitch). If frequency of stimulation is faster than time taken for muscle to relax, there can be constant tension in muscle (fused tetanus)
104
What does tetrodotoxin do?
Inhibits sodium channels so no depolarisation in membrane and no action potential
105
What does dendrotoxin do?
Inhibits potassium channel so membrane stays depolarised meaning continued release of ACh
106
What does omegacnotoxin do?
Inhibits calcium channels so vesicles can't fuse and muscles cannot contact as no ACh is released
107
What does botulinum toxin do?
Inhibits transmission at neuromuscular junctions. Leads to muscle weakness, paralysis and death. For vesicle to be able to fuse with membrane, there must be SNARE proteins, toxin cleaves these proteins so there is no vesicle fusion and no ACh is released.
108
What is aerobic exercise?
Typically long sustained, low level exercise.
Stimulation of slow fibres.
Conversion of IIx into IIa.
Increased fatigue resistance. No change in muscle strength.
109
What is anaerobic exercise?
Typically brief, intense exercise.
Stimulation of fast fibres.
No change in number of muscle fibres.
Enlargement of myofibril size by addition of myofillaments. Causes increased diameter of muscle fibre.
110
How does energy delivery during exercise change?
Immediate energy supply- meets the immediate demand for ATP, relies on ATP and phosphocreatine supplies in muscle, stores are quickly depleated.
Anaerobic metabolism- glycolysis under anaerobic conditions to supply ATP. Efficiency is quickly reduced.
Oxidative energy- via oxidative phosphorylation.
111
Describe non-oxidative energy release
- Substrates enter glycolysis at 2 points.
- Glycogenesis of glycogen produces glucose-1-phosphate.
- Glucose-1-phosphate converted to glucose-6-phosphate which enters glycolysis at reaction 2.
- Uptake of glucose from blood Bly GLUT4.
- Glucose enters glycolysis pathway.
- Pyruvate produced which is converted to lactic acid.
- Process is inefficient compared to oxidative phosphorylation.
- H+ from lactic acid lowers cell pH and leads to muscle fatigue.
- But produces ATP in the absence of oxygen.
112
Describe the aerobic (oxidative) energy release
- As tissue oxygen delivery increases, energy production via oxidative phosphorylation is stimulated.
- Process is slower but is more efficient.
- Glucose is sourced from blood, following breakdown of glycogen.
113
What are the different types of muscle fatigue?
Central fatigue- Minor factor in trained exercise (brain sending messages you are tired).
Peripheral fatigue- At the level of the muscle fibre:
High frequency fatigue- alteration in cell Na/K balance. Particularly in type II.
Low frequency fatigue- reduced release of Ca2+ from sarcoplasmic reticulum, more apparent at low frequency stimulation. Type I fibre.
ATP depletion- intense stimulation can cause large drops in ATP near sites of cross-bridge formation.
Lactic acid buildup- high rates of lactate production leads to cellular acidification.
Glycogen depletion.
114
What is cardiac muscle, describe its structure
- Muscle specific to the heart
- Cardio myocytes are striated like skeletal muscles
- Myocytes are shorter and more branched. join together at intercalated disk.
- Electrical coupling between adjacent myocytes at intercalated disk by gap junctions.
- Action potential initiated by pacemaker cells of sinoatrial node and propagates between cells via gap junctions.
115
How is smooth muscle controlled?
More complex, can involve circulating hormones, autonomic nervous system input of inflammatory mediators.
116
Describe calcium release in skeletal muscles
- L-type calcium channels in membrane of t tubule open by depolarisation.
- In membrane of sarcoplasmic reticulum, there are ryanodine receptors which are a type of calcium channel.
- Action potential comes down T tube, opening L type calcium channels.
- Calcium comes into cell through L type calcium channels.
- Calcium can also increase due to a link between L type calcium channels and ryanodine receptors.
- Due to this, skeletal muscle doesn't need extracellular calcium for contraction.
117
Describe calcium release in cardiac muscle
- Has T tubules, but instead of tries, there is a dead (one branch of SR)
- Interaction between T tubule and dead is on Z line of sarcomere.
- Different isoform of ryanodine receptors and no tethering between t tubules and ryanodine receptors.
- Depolarisation opens calcium channels in t tubule, calcium enters cardiomyocytes and stimulates ryanodine receptors to open and release calcium (calcium induced calcium release)
118
Describe how calcium can be removed
Can be removed across cell membrane by means of plasma membrane calcium ATPase or electrogenic sodium/calcium exchanger.
Or back into SR via sarco/endoplasmic reticulum calcium ATPase.
119
Describe calcium release in smooth muscle
- Lack t tubules and triad/dyad structures.
- instead have invaginations called caveolae with voltage gated activated calcium channels.
- Change in the membrane potential causes channels to open, calcium floods into cell and calcium induced calcium is released from stores.
120
Describe the differences between sarcomere contraction in skeletal, cardiac and smooth muscle
Its similar in skeletal and cardiac muscle:
-Calcium binds to TnC leading to conformational change, moving tropomyosin and Tnl.
-Change in position reveals actin binding site.
-Contraction can continue whist calcium levels are high.
In smooth muscle:
-No troponin.
-Calponin and caldesmon inhibit interaction between actin and myosin.
-Calcium binds to calmodulin which activates MLCK which phosphorylates myosin head, activating it.
-Muscle contraction continues whilst MLCK is activated, even if calcium levels drop.
121
What are the functions of circulatory systems?
- Deliver gases and molecules for nutrition, growth and repair.
- Distribution of hormones for chemical signalling.
- Dissipation of heat.
- Mediates inflammatory and host defence response to invading microbes.
- Meet changing demands of organism such as sleep and awake, rest and exercise etc.
122
What are the building blocks of the vascular wall of blood vessels?
1. Endothelial cells- line blood vessels in continuous layer. Junctional complexes keeping cells together.
2. Elastic fibres- provide stretch for the vessels due to weave and loose attachment of fibres to other elements in vessels.
3. Collagen fibres- maintain integrity of blood vessels preventing bursting.
4. Smooth muscle cells- establish diameter of vessels.
123
Describe the structure and function of elastic arteries
- Largest arteries
- Layers of elastic tissue replace smooth muscle meaning walls easily stretch without tearing
- Elastic fibres force blood to move even when ventricles are relaxed
124
Describe the structure and function of muscular arteries
- Medium sized arteries
- Smooth muscle arranged circumferentially
- Capable of greater vasoconstriction and vasodilation to adjust to rate of blood flow
- Vascular tone; state of partial contraction maintains vessel pressure and efficient flow
125
Describe the structure and function of arterioles
Smooth muscle enables regulation of blood flow into capillaries
- Terminal regions known at metarterioles
- Pre capillary sphincters monitor blood flow into capillary
126
Describe the structure and function of venules
- Post capillary venules are porous so they act as exchange sites
- Muscular venules are thin smooth muscle layers and are less muscular than arterioles
- Thin walls allow expansion so they're excellent reservoirs for blood
127
Describe the structure and function of veins
- Less muscular and elastic but are distensible to adapt to variations in blood pressure and volume
- Act as reservoirs
128
Describe the structure and function of large veins
- More muscular
| - Valves prevent back flow
129
What are the roles of capillaries?
- Exchange site of gases, water, nutrients and waste products.
- Glomerular filtrate
- Skin temp regulation
- Hormone distribution
- Platelet delivery
130
What is plasma and what are some of the proteins within it?
- Watery solution of electrolytes, plasma proteins, carbohydrates and lipids.
- Can be separated by electrophoresis and the proteins include:
- Albumin
- Fibrogen
- Globulis
- Other coagulation factors
131
What are erythrocytes? Describe their structure and functions
RBCs
Most abundant element of blood
Non nucleated biconcave disk
Shape maintained by cytoskeleton anchored to plasma membrane
O2 carriage from lungs to systematic system
Co2 carriage from tissues to lungs
Buffering of acids and bases
132
What are the different types of leukocytes?
Can be granulocytes:
-Neutrophils- phagocytose bacteria
-Eosinophils- combat parasites and viruses
-Basophils- release IL-4, histamine, heparin and peroxidase
Or non-granular:
-Lymphocytes, which mature into T or B cells
-Monocytes- macrophages and dendritic cells
133
What influences blood viscosity?
- Heamocrit
- Fibrinogen plasma concentration
- Vessel radius
- Linear velocity
- Temperature
134
Where in an arteriole is RBC movement fastest?
In the centre, blood travels in parabolic profile meaning maximal velocity at centre
135
What is turbulent blood flow?
At high flow rates (above critical velocity) blood flow is no longer laminar but turbulent.
In turbulence, parabolic profile is blunted.
It occurs when radius is large or velocity is high.
Its clinically significant because laminar flow is silent and turbulent flow murmurs.
136
What is haemostasis and how is it achieved?
Prevention of haemorrhage through:
- Vasoconstriction
- Increased tissue pressure
- Platelet plug
- Coagulation and clot formation
137
What triggers endothelial cell von willebrand factor release?
- High shear forces
- Cytokines
- Hypoxia
138
What is a blood clot?
A semisolid mass of erythrocytes, leukocytes, serum proteins and mesh of fibrin.
139
What are the two clotting pathways?
Intrinsic pathway- surface contact with activation on membrane of activated proteins
Extrinsic pathway- activated when blood contacts material from damaged cell membranes
Both end in common pathway that generates thrombin and stable fibrin.
140
What is thrombus?
Intravascular blood clot
141
What is the pericardium?
Fluid filled sac surrounding the heart, protecting it and preventing infection
142
What are the valves within the heart and where are they located?
- Atrioventricular valves (mitral and tricuspid) are connected to cardiac wall by chorade tendinae and papillary muscles.
- Semilunar valves are between atria and ventricles and have small fibrous nodules coming together to fill opening.
143
What are the three layers of the heart wall?
Epicardium; has fat on surface mainly loose connective tissue
Myocardium; striated muscle making up main tissue of heart wall. Cardiac muscle cells contained in collagen
Endocardium; inner layer of heart is smooth muscle and elastic fibres
144
What are t-tubules in cardiac muscle and what is their role?
- Sarcolemma forms deep invaginations called t-tubules
| - T-tubules enable current to be relayed to the cell core releasing calcium
145
Describe the depolarisation sequence of the cardiac cycle
- Cells of SAN spontaneously depolarise to fire action potentials at regular intrinsic rate
- Cardiac cells electrically coupled through gap junctions conduct cell to cell through right and left atrial muscle (atrial systole)
- 0.1 second later signal arrives at AVN
- Impulse spread prevented by fibrous AV ring
- Impulse from AV node to HIS purkinje fibre system within muscles of ventricles (leads to ventricular systole)
146
Describe atrial systole
Depolarisation of atria following stimulation from SAN. Contraction of stream causes increase in atrial pressure. As ventricles are relaxed and mitral/ tricuspid valves open the ventricles further fill with blood.
147
Describe isovolumetric ventricular contraction
Following electrical activation via Purkinje fibres, ventricles contract and pressure increases. When ventricular pressure exceeds atrial pressure, mitral and tricuspid valves close producing the 1st heart sound. Pressure increases markedly but volume remains the same.
148
Describe rapid ventricular ejection
Pressure continues to rise until it exceeds aortic pressure. Semilunar valves open, rapid ejection of blood driven by pressure gradient. Most of stroke volume ejected in this phase. Ventricular volume falls dramatically and arterial pressure rises due to large volume received. Atrial filling begins
149
Describe reduced ventricular ejection
Ventricles begin to depolarise and pressure falls as no longer contracting. As semilunar valves still open, blood continues to be ejected but at reduced rate and ventricular volume falls. Arterial volume also falls as blood moves into 'arterial tree'
150
Describe isovolumetric ventricular relaxation
Begins after ventricular pressure falls below arterial pressure. Mitral and tricuspid valves open. Ventricles begin to fill and volume increases rapidly but pressure remains low
151
Describe reduced ventricular filling
Longest phase of cardiac cycle and includes last portion of ventricular filling
152
What is being recorded during the P wave, QRS complex and T wave in an ECG?
P wave- depolarisation of atria
QRS complex- depolarisation of ventricles
T wave- depolarisation of ventricles
153
What is blood flow determined by?
- Pressure difference between vessel inlet and outlet
| - Resistance of vessel to blood flow
154
What factors cause resistance to blood flow?
Blood vessel diameter
Vessel length
Series/ parallel arrangement
Blood viscosity
155
What are systolic and diastolic pressure?
Systolic- highest arterial pressure in arteries after blood is ejected from ventricles during systole
Diastolic- lowest arterial pressure during ventricular relaxation
156
What are the 4 components of the sympathetic NS that elevate BP?
- SAN to increase heart rate
- Cardiac muscle to increase contractility
- Arterioles to produce vasoconstriction and increase TPR
- Veins to produce vasoconstriction and decrease unstressed volume
157
What longer term controls for arterial pressure are in place?
- Renin-angiotensin system
- Chemoreceptors for O2 in carotid and aortic sinus bodies- stimulates arteriole vasoconstriction
- Chemoreceptors for CO2 in brain stimulates arteriole vasoconstriction
158
How does chronic hypertension come around?
-Baroreceptors reset and so hypertension is maintained and not corrected
159
What are some of the treatments for hypertension
```
ACE inhibitors
ARBs
Diuretics
Beta blockers
Calcium channel blockers
Alpha blockers
Renin inhibitors
```
160
What are the two zones that the lungs are divided into?
Conducting zone- the way of transporting gases into the respiratory zone. Includes structures in the mouth, nose and upper airways. Conditions incoming air: filters it using hairs, warms it to body temperature and humidify.
Respiratory zone- When the alveoli start appearing.
161
Describe the structure of the bronchi
- Upper areas reinforced with cartilage rings to prevent airways from collapsing
- Layers of smooth muscle which can contract to reduce the diameter
- Mucous glands help trap particles when mucus is secreted.
162
Describe the structure of the respiratory epithelium
- Lining lumen of airways is epithelial layer
- Layer of ciliated cells helps direct mucus up throat and moves small particles out of lungs
- Goblet cells are responsible for producing mucus
- Nerve endings detect noxious chemicals in airways
163
Describe the process of quiet inspiration
Involves primary muscles of inspiration
Diaphragm contracts and moves down, lungs expand and pressure is lower than atmospheric so air moves into lungs
External intercostal muscles between ribs contract helping thoracic body expand
164
Describe the process of forced inspiration
As well as primary muscles, accessory muscles of inspiration are used
Scalenes attached to neck and rib cage lift up and forward
Sternocleidomastoid muscles attach to sternum and lift it up and forward
Neck and back muscles move pelvic girdle to expand rib cage
165
Describe the process of quiet expiration
Passive process using elastic recoil
Relaxation of external intercostal muscles and diaphragm
Lung volume reduces, pressure increases and air moves out of lungs
166
Describe the process of forced expiration
Accessory muscles
Abdominal muscles push diaphragm up
Neck and back muscles
Internal intercostal muscles help bring rib cage back down to original position
167
What is the pleura?
Pleural cavity is filled with secretions
Prevents lungs from sticking to chest wall
Enables free expansion and collapse of lungs
168
What is compliance?
Measure of elasticity. Change in volume over the change in pressure.
Reflects how easy it is for the lungs to expand during breathing using the change in pressure in the intrapleural space.
169
What does low compliance mean and give an example of when it occurs
Means more work is needed to inspire
| E.g. pulmonary fibrosis where there is a build up of scar tissue
170
What is high compliance and give an example of when it occurs
Difficulty expiring due to loss of elastic tissue e.g. emphysema
171
What are the components of elastic recoil in the lungs?
1. Anatomical component- the elastic nature of cells and the extracellular matrix
2. Surface tension at the air fluid interface. Alveoli are fluid lined and develop an aspect of surface tension. Surface tension develops due to differences in the forces on water molecules at the air/water interface.
172
What is vital capacity?
Deepest breath in and expiring as much as possible
173
What is residual volume?
Air left in lungs after expiring as much as possible
174
what is total lung capacity?
Vital capacity and residual volume added together
175
What is FEV1?
Fill lungs as much as possible, breathe out as quickly as possible, amount of air breathed out in one second.
176
What is the importance of poiseuille's law?
Resistance of airway is proportional to 1/radius to the power 4 so a small change in radius will have a big impact on resistance and therefore flow rate.
177
What factors impact airway resistance?
-Airway diameter
Mucus secretions
-Oedema
-Airway collapse
178
What controls bronchial smooth muscle?
ANS system:
-Parasympathetic, Ach released from vagua, acts on muscarinic receptors leading to constriction.
Sympathetic- release of norepinephrine from nerves, weak agonist leads to dilation.
Humoural factors:
-Histamine released during inflammatory processes leads to constriction.
179
What is Dalton's law?
The total pressure of a mixture of gases is the sum of their individual partial pressures
180
Describe the structure of haemoglobin
- Tetrameric structure with 4 subunits coming together
- Each unit consists of haem unit and globin chain
- In adult Hb, there are 2 alpha globin chains and 2 beta globin chains
- In foetal Hb, there are 2 alpha and 2 gamma globin chains
181
Describe how oxygen binds to haemoglobin
- For oxygen to bind, iron has to be in Fe2+ state. Enzyme methaemoglobin reductase converts Fe3+ back into Fe2+.
- Haemoglobin exists in tense and relaxed state
- In relaxed state it has a high affinity for oxygen
- If one oxygen binds to one unit, all other units flip into relaxed state
182
Describe the oxygen haemoglobin dissociation curve
- At low partial pressures of oxygen, all Hb is in a tense state, as partial pressure of oxygen increases, some Hb binds to oxygen and flips into a relaxed state causing the rapid binding oxygen
- saturation point is reached
183
Describe the effect of temperature on the oxygen dissociation curve
- If haemoglobin is warmer, the curve shifts right, meaning Hb at any partial pressure can't carry as much oxygen and saturation decreases
- When cooler, curve shifts left meaning Hb holds onto oxygen more tightly so lower partial pressures are needed for oxygen release
184
What is the effect of pH on the oxygen dissociation curve?
If blood becomes more acidic, Hb is less efficient at carrying oxygen and oxygen is released
185
What shift is seen in the oxygen dissociation curve in foetal Hb?
A leftward shift, at any partial pressure, Hb has a higher affinity meaning it allows efficient uptake from mothers circulation.
186
How is Co2 carried in the blood?
Carbonic acid
Bicarbonate
Carbonate
Carboamino compounds
187
How is CO2 transported in the blood?
RBC in capillary is going past respiring tissue. Co2 crosses endothelial layer of capillary and enters blood. Small proportion remains in plasma. Majority of CO2 goes across RBC membrane. Some binds to haemoglobin to form carbamino compounds, it isn't binding where the oxygen binds. RBC becomes more acidic inside because as carbon dioxide is bound, H+ is released and oxygen is offloaded to tissues. Majority of CO2 produced by respiration is carried as bicarbonate dissolved in plasma. When RBCs get to lungs, process is in reverse. Chloride bicarbonate exchanger switches directions and chloride moved out. Carbonate back into CO2 and can leave RBC across capillary membrane, being released into gas in lungs. Co2 is then lost from the body.
188
What are the two types of lung disease?
Obstructive- reduction in flow through airways
| Restrictive- reduction in lung expansion
189
What causes obstructive lung diseases?
Result of narrowing of the airways. Could be due to:
- Excess secretions
- Bronchoconstriction (asthma)
- Inflammation
190
What are some obstructive lung diseases?
- Chronic bronchitis
- Asthma
- COPD
- Emphysema
191
What are the two types of asthma and what are the treatments?
Atopic- allergies.
Non-atopic- Respiratory infections, cold air, stress, exercise, drugs.
Treatment includes Beta 2 adrenoreceptor agonists e.g. salbutamol to dilate the airways or inhaled steroids to reduce inflammation.
192
What are restrictive lung diseases caused by?
-Reduced chest expansion due to chest wall abnormalities and muscle contraction deficiencies or loss of compliance due to ageing, increase in collagen or exposure to environmental factors such as asbestos.
193
How is breathing controlled?
The basic respiratory rhythm is generated by centres in the medulla.
Respiratory pattern can be modified.
DRG controls quiet inspiration by sending signals to respiratory muscles
VRG controls inspiration and expiration during forceful inspiration and expiration.
194
Describe the central control of respiration
- Pre-botzinger complex generates basic rhythm and sends signals to dorsal and ventral respiratory group.
- Signals coming from vagus and glossopharyngeal nerve and out through phrenic nerves.
- Pneumotaxic centre and agnostic centre in pons control breathing rate by altering pattern of firing.
- Pneumomtaxic centre increases rate by shortening inspirations.
- Apneustic centre increases depth and reduces rate by prolonging inspirations
195
What are the intra and extracellular cation concentrations?
Intracellular potassium is high (148mM) but extracellular is low (5mM)
Intracellular sodium is low (10mM) but extracellular is high (140mM)
196
What are the intra and extracellular anion concentrations?
Chloride has low intracellular concentration (4mM) and high extracellular (103mM)
High intracellular protein concentration (55mM) low extracellular (15mM)
197
Describe the daily balance of sodium
Typically ingest 150 mMoles per day through diet.
We must lose 150 mMoles per day to maintain equilibrium.
Around 10 mMoles per day lost in stool and sweat.
140 mMoles lost through urine.
198
Describe the daily balance of water
Ingest 2.6l of water per day.
Lose 1.1l per day through respiration, stool and sweat.
Lose 1.5l per day through urine.
199
What is renal failure and what are the different types?
A fall in glomerular filtration rate, leading to increase in serum urea and creatine.
Acute renal failure is reversible and there is no change to Hb levels and renal size stays the same.
Chronic renal failure is irreversible meaning dialysis or transplant is needed. Fall in Hb levels and renal size. Peripheral neuropathy (nerve damage) is present.
200
What are the causes of chronic renal failure?
Glomerulonephritis
Diabetes mellitus
Hypertension
Polycystic kidney disease
201
What is the treatment for renal failure?
- Treating the cause of the failure
- Treat the reversible factors and complications such as a diet with restricted protein, salt and water.
- Reduction of symptoms to slow the progression and need for dialysis and transplant.
202
What happens in the glomerulus?
Filtration
Plasma enters via afferent arteriole into glomerular capillaries, plasma moves out into Bowmans capsule. The rest leaves via efferent arteriole.
Filtration barrier lets water and small molecules through but restricts blood cells and proteins.
Ultrafiltrate is protein free plasma.
203
What are the 2 basic pathways for tubular transport?
Transcellular (across cell, ions solutes and water which use transport proteins to move across apical membrane across cell and leave via basolateral membrane into peritubular capillaries.
Paracellular (between cells through tight junctions)
204
What is the role of the proximal tubule?
Its the first part of the nephron after the Bowman's capsule.
Beginning of proximal tubule is protein free ultrafiltration.
It's a bulk reabsorbing epithelium and it reabsorbs 70% of total filtrate.
100% of glucose and amino acids are reabsorbed.
90% of HCO3- is reabsorbed.
205
Describe how a sodium gradient is created in the proximal tubule
- Sodium potassium ATPase sits on basolateral membrane of proximal tubule cell. This is a primary active transport protein which hydrolyses ATP to transport 3 sodium ions out and 2 potassium ions into cell.
- Movement against electrochemical driving force.
- Basolateral potassium channel.
- Set up driving force for sodium uptake at apical membrane of renal proximal tubule.
- Set up negative membrane potential which is potential gradient for sodium.
- Intracellular sodium conc is kept low and extracellular is high creating a gradient.
206
What is the role of the sodium glucose cotransport protein?
On the apical membrane of proximal tubule.
Uses sodium gradient to bring glucose into cell
Glucose then moves down conc gradient across basolateral membrane
2 types: SGLT1 and SGLT2.
207
Describe the role of the sodium amino acid co transport proteins in the proximal tubule
Use concentration gradient of sodium to transport amino acids into cell
Sodium that comes in then leaves via sodium-potassium ATPase.
Amino acid transporters on basolateral membrane lead to amino acid reabsorption.
208
What is the role of the NaPiII and what are the risks if it isn't working?
Binds sodium and phosphate, using sodium, electrochemical driving force to bring phosphate into cell. Phosphate then diffuses down electrochemical gradient across basolateral membrane into peritubular capillaries.
Phosphate must be retained for example for ATP and bone formation.
For people whose NaPiII isn't working, they have increased calcification and are at greater risk of intraluminal stones forming.
209
Describe the process of bicarbonate reabsorption by NHE3
- Sodium comes into cell, as this happens, a hydrogen ion leaves
- Hydrogen binds with bicarbonate to form carbonic acid (H2CO3)
- Under influence of enzyme sitting on extracellular apical membrane, called carbonic anhydrase, H2CO3 dissociates into carbon dioxide and water.
- Carbon dioxide diffuses into cell. Water moves between cells through water channels (aquaporins)
- Carbonic anhydrase inside cell splits H2CO3 into hydrogen ion and bicarbonate
- Bicarbonate leaves via basolateral membrane.
- Hydrogen is recycled.
- Reabsorbed bicarbonate goes into plasma and plays ole in regulation of plasma pH.
210
What is the function of the late distal tubule, connecting tubules and cortical collecting duct?
- Concentration of urine
- Reabsorption of Na+ and H2O
- Secretion of K+ and H+
211
What 2 cell types are the late distal tubule and cortical collecting ducts made from?
Principal cell- Important for Na+ and H2O reabsorption and K+ and H+ secretion.
Intercalated cell- can be in alpha or beta form important for wither H+ secretion and reabsorption or HCO3- reabsorption and secretion.
212
Describe action at the principal cells
- Again has sodium potassium ATPase and basolateral potassium channel setting up the driving force for sodium influx.
- Epithelial sodium channel, when open allows sodium to move into principal cells, sodium then lost over basolateral sodium potassium ATPase, so net reabsorption of sodium.
- This then drives reabsorption of water as there is an osmotic driving force, water moves across apical membrane through aquaporin 2 water channel. It then leaves the basolateral membrane through aquaporin 3 and 4.
- Aquaporin 2 is the rate limiting step, aquaporin 3 and 4 are constitutively active meaning they’re always in the basolateral membrane and are open.
213
Describe action at the alpha intercalated cell
Secretes halogen ions and absorbs bicarbonate
Proton pump on apical membrane. Uses ATP to pump H+ against electrochemical driving force
Halogen ions go into tubular fluid and are lost in urine
Bicarbonate chloride exchanger AE1 and chloride channel on basolateral membrane
-Chloride is recycled on basolateral membrane allowing bicarbonate to be taken from inside cell, across basolateral membrane
214
What is the role of the loop of Henle?
- Concentration of urine
- Reabsorption of Na+, Cl- and H2O
- Reabsorption of Ca2+ and Mg2+
- Site of action of loop diuretics
215
Describe action at the thick ascending limb
- Sodium potassium ATPase and basolateral potassium channel set negative membrane potential and low intracellular sodium concentration.
- Sodium potassium 2 chloride cotransporter protein (NKCC2).
- Transporter utilises electrochemical driving force to bring sodium ion, 2 chloride ions and a potassium ion into the cell.
- Sodium then leaves cells via ATPase.
- Chloride accumulates and then leaves down electrochemical gradient via chloride channels on the basolateral membrane leading to net reabsorption.
- Net reabsorption of sodium and chloride into interstitial fluid sets up concentration gradient for water reabsorption in other parts segments.
- Barttin is a protein classed as a beta subunit and regulates CLCK. CLCK only function normally when barrtin is also present.
- Potassium is recycled on apical membrane through ROMK (Kie1.1) allowing potassium to be recycled.
- Absorption of Ca2+ and Mg2+ follows sodium and chloride through paracellular transport.
216
Describe action in the early distal tubule
- Reabsorption of Na+ and Cl-.
- Reabsorption of Mg2+.
- Sensitive to thiazide diuretics.
- ATPase and basolateral potassium channel has the same role.
- Sodium uptake by NCC on apical membrane meaning Cl- is also transported.
- Sodium lost by sodium potassium ATPase.
- Chloride leaves through CLCK like chloride channel. Different version to the one in the thick ascending limb.
- Magnesium travels through trip channels. When open, magnesium enters cell.
- Still unknown what magnesium loss pathway on basolateral membrane is.
217
What is gitelmans syndrome?
```
Genetic inheritance (recessive)
Salt waisting and polyuria
Hypotension Hypokalaemia
Metabolic alkalosis
Hypercalcuria
Known as different to Bartters syndrome due to genetic testing
Mutation in NCC protein
```
218
What is Bartters syndrome?
- Genetic inheritance- recessive.
- Salt wasting (lose too much sodium and chloride in urine) and polyuria (increase in urine flow rate)
- Hypotension as extracellular fluid volume is reduced.
- Hypokalemia (low plasma potassium).
- Metabolic alkalosis.
- Hypercalciuria (too much calcium in urine).
- Nephrocalcinosis (kidney stone formation).
- Mutated proteins could be NKCC2, ROMK (Kir1.1) or CLCK.
219
Where is vasopressin produced and secreted from?
- Released from posterior pituitary gland.
- Produced in cell bodies of neurosecretory neurons which originate in the hypothalamus
- Axons of neurosceretory neurons travel down the posterior pituitary through the pituitary stalk.
- Vasopressin is made in cell bodies and travels down axon and is stored in posterior pituitary in vesicles.
220
Describe the release and the role of vasopressin
- Action potential in neurosecretory neurons causes fusion of vasopressin containing vesicles with membrane, releasing it into circulation through capillaries, taken all over the body in venous blood supply. Target organ is kidneys
- Plays vital role in body osmolality
- Vasopressin works to conserve water.
- Increase in body fluid osmolality triggers vasopressin release.
- We retain water at the level of the kidney meaning we conserve water and the concentration of plasma falls back to the normal level.
221
Describe the regulation of vasopressin release
- Increase in release of vasopressin:
- Ingestion of solutes or vasopressin deficiency
- Stress stimulates release
- Nicotine stimulates release
- Ecstasy also stimulates release
- Decrease in release:
- Result of excessive fluid ingestion
- Drugs such as alcohol
222
Describe the principal cell H2O model
- Vasopressin in the peritubular capillaries diffuses into interstitial fluid and binds to the V2 receptor on basolateral membrane.
- Binding to V2 stimulates PKA which mediates phosphorylation leading to insertion of vesicles under apical membrane.
- Fuse with membrane and at this membrane are the aquaporin 2 water channels
- Leads to an increase in aquaporin 2 water channels in membrane and increase in water reabsorption.
223
What are the two types of diabetes insipidus?
Central DI- individual releases no vasopressin. Treatment with DDAVP nasal spray which is an artificial vasopressin.
Nephrogenic DI- Defect at level of kidney meaning they lose ability to respond to vasopressin. Could be defect in V2 receptor or H2O channel defects.
224
What is aldosterone and when is it released?
- Released from cortex of adrenal gland in zone called zona glomerulosa layer.
- Mineralocorticoid as it regulates minerals (plasma sodium, plasma potassium and volume of body fluid)
- Released in response to:
1. Increase in plasma K+
2. Decrease in plasma Na+
3. Decrease in ECF volume via renin-angiotensin
225
Describe the action of aldosterone
- Released from adrenal gland into circulation and to kidneys
- Leaves peritubular capillaries and acts on late distal tubule and collecting duct.
- Causes increases reabsorption of Na+ and therefore increased reabsorption of water.
- Aldosterone is a steroid hormone meaning its membrane soluble and can pass the lipid bilayer.
- Diffuses into cells where there are cytosolic receptors (mineralocorticoid receptors). -Aldosterone binds to these receptors, and this receptor, aldosterone complex, moves to nucleus of cell where it stimulates RNA transcription and protein synthesis.
- Stimulates synthesis of proteins involved in sodium reabsorption, potassium ion secretion and halogen ion secretion.
- Genomic action is slow.
- Net effect of stimulation of principal and intercalated cells is that there is more sodium absorption brining sodium content of plasma up, water follows this sodium, brining ECF volume up, there is a decrease in plasma potassium and a decrease in plasma halogen ions as more are secreted.
- This system is coordinated with the renin-angiotensin system.
226
Describe the renin angiotensin system
-Regulates body fluid volume, plasma sodium and plasma potassium
-Renin released from juxtaglomerular apparatus
-Macula dense cells assess composition and flow of fluid
-Granular cells contain renin and release into plasma, starting cascade
-Fall in ECF volume stimulates release of renin into circulation
-In blood vessels renin enhances production of angiotensin 1 and is converted to angiotensin 2 with angiotensin converting enzyme found in capillaries
-Angiotensin 2 acts at level of zona glomerulosa and stimulates aldosterone release
Also has an effect on arterioles, causing vasoconstriction to bring blood pressure up if fluid is lost
-Aldosterone increases plasma Na+content and increases ECFV as water follows Na+
-Blood pressure increases back to normal
227
What are the functions of the GI tract?
-Digestion and absorption of nutrients achieved through:
Motility to propel ingested food
Secretions from associated glands
Digestion/ hydrolysis into absorbable molecules
Absorption into blood stream of nutrients, electrolytes and water
228
Describe the structure of the GI wall
1. mucosal layer with epithelial cells, lamia propria (connective tissues with blood and lymph vessels) muscularis mucosae (changes shape due to contraction
2. sub mucosal layer with collagen, elastin, glands and blood vessels
3. circular and longitudinal muscle
4. serosa, outermost layer of connective tissue
5. 2 main plexuses contain nervous system of GI tract
229
What is the enteric nervous system?
Collection of nerve plexuses surrounding GI tract which act as nervous system of GI tract.
230
Describe parasympathetic control of the GI tract
vagus or pelvic nerve
| postganglionic neurons release either ACh (cholinergic) or peptides (peptidergic)
231
Describe the sympathetic control of the GI tract
Sympathetic postganglionic nerve fibres are adrenergic (release norepinephrine)
Nerve fibres are mixed afferent and efferent i.e. sensory and motor information is relayed between GI tract and CNS coordinated by plexuses
232
What are the classes of GI peptides?
Hormones- from GI endocrine cells
Paracrines- from endocrine cells
Neurocrines- released form neurone following action potential
233
What are the two types of contraction in the GI tract?
Phasic-periodic contraction and relaxation
| Tonic- constant level of contraction/ tone
234
What are the 3 phases of swallowing?
1. Oral (tongue forces bolus towards pharynx)
2. Pharyngeal (soft palate is pulled upwards and epiglottis moves to cover opening to larynx, upper oesophageal sphincter relaxes, food can pass into oesophagus)
3. Oesophageal
235
What are the 3 phases to motility in the stomach?
1. Receptive relaxation in thin walled road stomach to receive food by reducing pressure and increasing volume
2. 3 muscular layers of caudad region contract to mix good with gastric juice from mucosal glands forming chyme
3. Gastric emptying through pyloric sphincter into small intestine- fat content and H+ slow emptying
236
What are the three sections of the small intestine?
Duodenum, jejunum, ileum
237
What is the role of the pancreas?
Solution rich in HCO3 secreted by centroacinar and ductal cells to neutralise H+ delivered from stomach
Enzymes secreted by acinar cells
Parasympathetic NS stimulates secretion
238
What is the role of the liver in the GI tract?
Secretes bile produced by hepatocytes
| Gall bladder stores and concentrates the bile
239
What are the 3 major functions of the large intestine?
Absorbs water and electrolytes
Makes and absorbs vitamin k and b
Forms and propels faeces
240
What is secreted in the mouth?
- 𝛼 amylase
- Lingual lipase breaking down triglycerides to diglycerides and fatty acids
- Mucus to lubricate food
241
What is secreted in the oesophagus?
- Mucus secreted from sub mucosal glands
| - Bicarbonate ions to protect against reflux of gastric acid
242
What is secreted in the stomach?
- HCl and pepsinogen initiating protein digestion
- Gastric and intrinsic factors for absorption of B12
- Mucus to protect stomach lining and lubricate stomach contents
243
What is secreted in the small intestine?
- Mucus
- HCO3-
- Pancreatic juice and bile
244
What is secreted in the large intestine?
-Mucus to protect lumen lining and for transit of stools
245
Describe the cells and their role in the stomach
- Opening of ducts are called pits which are lined with epithelial cell which secrete HCO3-.
- Mucous cells secrete mucus
- Parietal or oxyntic cells secrete HCl and intrinsic factor for absorption of B12 in ileum.
- Chief/ peptic cells release pepsinogen which will become protease enzyme pepsin once cleaved and activated.
- G cells secrete gastrin
- D cells secrete somatostatin
246
Describe gastric secretion from parietal cells
- Secrete HCl to acidify gastric contents to pH 1-2 enabling conversion of inactive pepsinogen to pepsin
- Allows protein digestion to begin
- Apical membrane contains hydrogen potassium ATPase and chloride channels
- Basolateral membrane contains sodium potassium ATPase and bicarbonate chloride exchanger
- In intracellular fluid, CO2 from aerobic metabolism combined with water to form carbonic acid,, which dissociated into hydrogen and bicarbonate ions. H+ ions are secreted across apical; membrane with chloride following so movement of HCl into lumen.
- At basolateral membrane, bicarb ion is absorbed from cell into blood via chloride bicarb exchanger.
- Eventually bicarb ion is secreted back into GI tract.
247
Describe how HCl secretion is regulated
- Secretagogues; released by secretion by binding to G protein coupled receptors o parietal cell membrane
- Histamine; paracrine hormones released from ECL cells in gastric mucosa in stomach. Diffuses to parietal cells and binds to H2 receptors. Receptor is coupled to adenylyl cyclase by Gs which when activated will regulate cAMP. This will then activate protein kinase A and will up regulate secretion of H+ ions into lumen.
- Acetyl choline; released from vagus nerve and innovates gastric mucosa and binds to M3 receptors. Second messengers are inositol triphosphate and calcium. It has stimulatory effect on H+ ions into lumen. ACh can indirectly increase H+ ion secretion by stimulating ECL cells to secrete histamine.
- Gastrin secreted by G cells in antrum of stomach. When it reaches parietal cells, it binds to CCKb receptor. Acts by same pathway as ACh.
- Somatostatin; secreted by endocrine D cells and directly inhibits by binding to receptors on parietal cells. Antagonistic effect on binding of histamine.
248
Describe secretion within the intestines
- Epithelial cells lining intestinal crypts secrete fluid and electrolytes. Villus cells absorb.
- Apical membrane contains chloride channels.
- Basolateral membrane contains sodium, potassium, chloride co-transporter in addition to a sodium potassium pump.
- Co transporter brings sodium, chloride and potassium ions into cell from blood.
- Chloride ion then diffuse into lumen, through chloride channels in apical membrane, these channels open in response to hormones and neurotransmitters. They bind to receptors on basolateral membranes which activates adenylyl cyclase and generates cAMP which then activates opening of chloride channels and this is then followed by paracellular sodium movement and therefore water.
249
Describe absorption in cells in the jejunum
- Net absorption of sodium potassium and chloride secretion of bicarbonate.
- Sodium moves into cell on apical membrane along with sugar or amino acids.
- Sodium potassium ATPase on basolateral membrane causes low intracellular sodium concentration providing driving force for sodium entry on apical membrane.
- Source of hydrogen ions for sodium, hydrogen ion exchange is intracellular carbon dioxide and water which are catalysed by carbonic anhydrase, dissociating into bicarbonate and hydrogen ion.
- Hydrogen is then secreted into lumen by sodium hydrogen ion exchanger.
- Net absorption of sodium bicarbonate.
250
Describe absorption in the ileum
Same transport mechanisms of the jejunum however also has a chloride bicarbonate exchanger on apical membrane and chloride ion transporter on basolateral membrane.
- When hydrogen and bicarbonate ions are generated intracellularly, the hydrogen ion is secreted into lumen by sodium hydrogen exchanger along with bicarbonate ion via chloride bicarbonate exchanger.
- Net effect is movement of sodium chloride into cell which is then absorbed.
251
Describe secretions from the pancreas
- Secretes bicarbonate ions and enzymes into small intestine to neutralise HCl from stomach.
- Enzymes digest carbohydrates, proteins and lipids into absorbable molecules.
- Acinar cells have receptors for CCK having a stimulatory effect to produce more enzymes.
- bicarbonate ions secreted into pancreatic juice, hydrogen ion transported into blood.
- Net effect is acidification of pancreatic venous blood.
252
Describe the process of absorption in the large intestine (colon)
- Apical membrane contains sodium and potassium channels for sodium absorption and potassium secretion.
- Synthesis of sodium channels induced by aldosterone.
- Increased sodium pumped out by sodium potassium ATPase, increasing intracellular potassium which is then removed by potassium channels.
253
Describe the absorption of carbohydrates
- 3 end products glucose, galactose and fructose
- Glucose and galactose absorbed into epithelial cells by either facilitated diffusion or sodium cotransporters (SGLT1)
- Basolateral sodium potassium ATPase sets up the gradient to drive the sodium movement into the cell.
- Fructose moves in via facilitated dissuasion by GLUT5 protein and out of basolateral membrane by GLUT2.
254
Describe the absorption of proteins
- Dietary proteins digested into absorbable forms (amino acids, dipeptides, tripe-tides)
- Absorbed by brush border in small intestine-Amino acids transported from lumen via sodium, amino cotransporter within the apical membrane.
- Amino acids then transported over basolateral membrane via facilitated diffusion.
- Di and tripeptides transported over apical membrane using hydrogen ion dependent co transporters.
- Inside cell, di and tripeptides are hydrolysed into amino acids and exit via facilitated diffusion.
255
Describe lipid absorption
- Cholesterol, monoglycerides and fatty acids are in micelles
- Micelle exterior lined with amphipathic bile salts-absorption across lumina; surface of enterocyte
- Intracellular digestive product reesterifiction and absorption into lacteals of lymphatic system.
256
What is secreted by beta cells in the pancreas?
Insulin, Proinsulin, C peptide, Amylin
257
What is secreted by alpha cells in the pancreas?
Glucagon
258
What is secreted by delta cels in the pancreas?
Somatostatin
259
Describe the regulation of insulin secretion
Regulation via islet beta cell receptors
-High blood glucose stimulates synthesis and secretion of insulin, low levels inhibit it
- Neural control; islets are richly innervated:
1. Sympathetic
- 𝛃 adrenergic stimulation increases secretion.
- 𝛂 adrenergic stimulation inhibits secretion.
2. Parasympathetic stimulation via vagus nerve releases ACh and increases insulin release.
- Humoral factors, GIP, amylin and somatostatin.
- Drugs, e.g. sulphonylureas acting on KATP channels increasing secretion of insulin.
260
Describe secretion in beta cells (pancreas)
- Glucose is most potent activator of secretion
- Glucose enters beta cells through GLUT2 specific channels by facilitated diffusion
- Glucose is metabolised inside the cell and is oxidised as a result of increasing levels of ATP which closes ATP dependant potassium channels
- This induces depolarisation which opens the Ca2+ voltage gated channels.
- Increase in intracellular calcium ions induces exocytosis of vesicles containing insulin.
- ACh and CCK act via G-protein coupled receptors to have the same effect.
261
Describe insulins action on blood glucose
- Insulin ensures excess nutrients are stored
- Target of insulin is liver, muscle and fat tissue
- Decrease blood glucose levels by binding to receptors on target cells
- Once bound, receptor promotes exocytosis of intracellular vesicles containing GLUT 4 receptor transporters
- This results in glucose uptake into cell increasing markedly
- Blood glucose concentration decreases
262
Describe insulin action in the liver
Insulin promotes formation of glycogen from glucose
| -Insulin inhibits glycogenolysis and gluconeogenesis.
263
What is the action of insulin in muscles?
Decrease blood amino acid concentration
Increases uptake of amino acids and proteins
Stimulation of proteins synthesis and inhibition of degradation
264
Describe the effect of insulin on adipocytes
Increase in GLUT4 transporters expression
Rapid glucose uptake
Glucose converted into fatty acids and stored as triglycerides
Increase in lipoprotein lipase
Insulin inhibits mobilisation and oxidation of fat stores and decreases circulating levels of FA
265
What is the function of the female reproductive system?
- Produce haploid gametes (eggs)
- Facilitate fertilisation of eggs by sperm
- Provides site for implantation of embryo within uterus
- Provide physical and nutritional needs throughout gestation
- Nurture the neonate after birth
266
Describe the structure of the ovary wall
Cortex- outer zone with germinal epithelial layer containing oocytes
-Inner medulla- contains blood vessels and lymph
267
Describe the structure of the uterine wall
Perimetrium
Myometrium
Endometrium-made of simple columnar cells and tubular glands and spiral arteries
268
What is the pH of the vagina and why?
3.5-4 to inhibit pathogens
269
What do FSH and LH do?
Stimulate ovary to secrete progesterone and oestrogen which produce mature gametes. They develop the ovum, maintain the corpus luteum and maintain pregnancy.
270
Describe the endometrial cycle and the 2 stages
Proliferative phase; Secretion is oestrogen increases and stimulates the growth of endometrium, glands, stroma and the spiral arteries elongate
Secretory phase; following ovulation, endometrial proliferation slows and thickness decreases slightly.
271
Describe the process of fertilisation
1. Sperm acrosomal reaction- penetration
2. Attached by a series of binding proteins. ZP3 is a sperm binding protein, using hydrolysing enzymes they can move through the zona pellucida.
3. Oocyte activation leads to cortical reaction- second metic division, prevents polyploidy
4. Fusion of haploid pronuclei- diploid zygote (46 chromosomes)
272
Describe the process of implantation
- Endometrium reception of blastocyst, low oestrogen and progesterone
- Blastocyst promotes endometrial Stromal cells
- Invasion of endometrium:
1. Hatching- degeneration of zona pellucida
2. Apposition- zona pellucida has completely cleared. Trophoblast os only in contact with endometrial epithelial layer
3. Adhesion is mediated by inter grin proteins which intracellularly interact with cytoskeletons of cells and extracellularly have receptors for matrix proteins
4. Invasion- areas of blastocyst have begun to invade endometrial layer.
273
Describe the role of the placenta
- Becomes life support of embryo
| - Supplies nutrients and removes waste material
274
What substances are transported from maternal to foetal blood?
Glucose by facilitated diffusion
Amino acids by secondary active transport
Vitamins by active transport
275
What is transported from foetal to maternal blood
Waste urea and creatine by diffusion
276
What are the hormonal changes in the 1st trimester?
- HCG rescues corpus luteum.
| - The corpus luteum continues secreting oestrogen and progesterone to support endometrium
277
What are the hormonal changes during the 2nd and 3rd trimester?
Placenta is primary hormone source
| Progesterone and oestrogen still secreted Prolactin secreted to develop mammary glands
278
Describe the quiescence stage of parturition
- Uterus is relaxed and is relatively insensitive to hormones that would cause contraction
- Prelude to birth from contraception
- Progesterone surpasses myometrial contractions
279
Describe the activation stage of parturition
- Near full term
- Preparation for birth
- Increase in cortisol which increases oestrogen and progesterone ration increasing contractility
- Oestrogen stimulates prostaglandin release which promotes formation of gap junctions, softens, thinks and dilates cervix.
- Gene expression of contraction associated proteins increased
280
Describe the labour stage of parturition
- Increases PG levels for myometrial contractions and cervical dilation
- Stages of labour and delivery:
- Dilation
- Expulsion
- Placental
281
Describe the recovery from birth
- Haemostasis; vasoconstriction of spiral arteries decreasing risk of haemorrhage.
- Decrease in placental oestrogen; regression of uterine vasculature
282
What is the role of lactation?
- Production of milk to support the baby
- Colostrum- first milk with high fat and protein content and antibodies
- Milk contains fat, sugar, protein
283
What is the effect of pilocarpine?
Slows heart rate
284
What antagonises the effect of pilocarpine?
Atropine
285
What effect does nicotine have?
Causes muscle contraction
286
What antagonises nicotine ?
Curare
287
what are the 4 classes of chemical communication?
Endocrine; chemical mediator will be secreted into bloodstream and distributed through blood, acting on receptors throughout the body. Useful for homeostatic responses where body coordinated response is needed.
Paracrine: signaling molecules act locally on neighbouring cells. May be of the same or different cell type.
Neuronal; Is very rapid and specific to a target cell between neurons at synapses.
Contact-dependant; mediator is anchored on cell surface of signaling cell so cell to cell contact is needed.
