Physiology and Pharmacology Flashcards
(410 cards)
1
Q
What is the function of the autonomic nervous system?
A
Unconscious control system of important bodily functions
2
Q
What are the two divisions of the autonomic nervous system?
A
Sympathetic and parasympathetic
3
Q
What are the sympathetic and parasympathetic nervous system responsible for?
A
Sympathetic - fight or flight response
Parasympathetic - Rest and Digest
4
Q
How does the sympathetic and parasympathetic nervous systems affect heart rate?
A
Sympathetic - increase heart rate
Parasympathetic - decrease heart rate
5
Q
How does the sympathetic and parasympathetic nervous systems involved in the male sexual function?
A
Parasympathetic - erection
Sympathetic - ejaculation
6
Q
What are the affects of sympathetic stimulation?
A
- Pupillary dilation
- Bronchodilation
- Heart rate and blood pressure rises
- Vasoconstriction in skin
- Glycogenolysis
- Metabolism increases
7
Q
What does the sympathetic nervous system target directly?
A
Adrenal glands
8
Q
Give examples of adrenergic system agonists?
A
Adrenaline, B2 selective agonists (salbutamol)
9
Q
Give an example of an adrenergic system antagonist?
A
B1 selective antagonists (Beta blockers)
10
Q
What is the role of adrenaline in the ANS?
A
- Activates alpha and beta receptors
- Blood pressure increases
- Dilates bronchi
11
Q
What is a clinical use of adrenaline?
A
used to treatment of anaphylactic shock - Epi-Pen
12
Q
What is the clinical use of B2 selective agonists of the adrenergic system?
A
Salbutamol
- Treats asthma
- Targets the bronchial smooth muscle
13
Q
What is the clinical use of B1 selective antagonists (Beta - blockers)?
A
- Used to treat high blood pressure
- Anxiety
- Angina
14
Q
What are the affects of parasympathetic stimulation?
A
- Pupillary constriction
- Decreases heart rate and blood pressure
- Promotes secretion (salivation) and mobility of digestive tracts
- Facilitates digestion
- Defecation and urination
15
Q
Name some differences between sympathetic and parasympathetic nervous system??
A
Parasympathetic has linger pre-ganglionic fibre, different anatomical location and different post ganglionic neurotransmitter
16
Q
Give an example of a cholinergic agonist?
A
Muscarine
17
Q
What are the effects of the cholinergic agonist Muscarine?
A
- Decreases blood pressure
- Increases salivation and sweating
- Abdominal pain
18
Q
What is the clinical use of the cholinergic agonist Muscarine?
A
Pilocarpine eye drops - treatment for glaucoma
19
Q
Give an example of a cholinergic antagonist?
A
- Atropine - blocks muscarinic receptors
20
Q
What are the effects of the cholinergic antagonist atropine?
A
- Inhibition of secretion
- Smooth muscle relaxant
- Pupillary dilation
- Increase body temperature
21
Q
What neurotransmitters are used in the parasympathetic and sympathetic nervous systems?
A
- Adrenaline
- ACh
- ATP
- Nitric Oxide
- VIP
- Substance P
22
Q
What are the clinical uses of nitric oxide?
A
Viagra
23
Q
What part of the brain controls the ANS?
A
Hypothalamus
24
Q
Give examples of cortical events that initiate an autonomic response?
A
- Panic attack - Initiate fight or flight
- Emotional stress/painful stimuli - Vasodialtion and decrease in blood pressure
- Chronic stress - increase in gastric acid secretion
25
Define receptor
Proteins that bind chemical mediators e.g. hormones, neurotransmitters
26
Define agonist
Drugs that bind to a receptor producing a response e.g. morphine
27
Define antagonists
Drugs that prevent the response of agonist -most clinical drugs e.g. atropine
28
Define ligand
Any molecule that binds to the receptor (agonist or antagonist)
29
What are the 4 types of drug receptors?
- Ion channels
- Enymes
- Carriers/Transporters
- Receptors
30
Give an example of drugs that target ion channels?
Apamin
- Stops pain nerve channels from admitting action potentials
- K+ channels booked
31
Give examples of drugs that target enzymes?
Aspirin
- binds to COX which signal inflammation
- therefore reduces inflammation, fever
Pargyline and clorgyline
- inhibits MaO enzyme which breaks down dopamine
- treats depression
32
Give examples of drugs that target transporters?
Fluoxetine (prozac)
- Works with transporters that takes up serotonin - keep levels high as a treatment for depression
- blocks transporter that pumps Ca2+ out the heart - used to treat fibrillation
33
What percentage of drugs interfere with receptors involved in chemical communication?
40%
34
What are the classes of receptors?
- Ligand gated ion channels
- G protein coupled receptors
- Kinase - linked receptors
- Nuclear receptors
35
What is the advantage of ligand gated ion channels as a receptor?
Involved in fast synaptic transmission
36
How do ligand gated ion channels open?
- Bound by an agonist
- Causing the membrane potential change
- Membrane depolarises for an excitatory neurotransmitter
- Membrane depolarisation is inhibited by inhibitory neurotransmitters
37
Give the structure of a nicotinic receptor?
- 5 subunits - heteromeric
- Receptors combine in distinct combinations
- Two molecules of ACh or nicotine must bind to open the channel
38
What is a G protein coupled receptor?
- Regulates an effector protein (enumerated or ion channel) via a G protein
- Generates a second messenger
39
What is the structure of G-proteins?
- 3 subunits alpha, beta and gamma
- Activated when GTP (phosphorylated)
- Rest when GDP (dephosphorylated)
40
How does a G-protein regulate an effector?
- Agonist binds to the receptor activating the G protein
- Causes the dissociation of alpha and beta subunits
- These bind with effectors
41
How do G protein couples receptors amplify signals?
Once a G protein has been activated and dissociates, the receptor is free to activate more G proteins. One receptor can activate many G proteins causing an amplification
42
What effectors are regulated by G proteins?
- Enzymes which regulated second messengers
| - Ion channels
43
What are the clinical uses of adrenoceptor agonists?
```
Cardiovascular system
- Cardiac arrest
- Anaphylaxis
- Hypertension
Respiratory system
- Bronchodilator (salbutamol)
```
44
What are the clinical uses of adrenoceptor antagonists?
- Hypertension
- Heart failure
- Anxiety
Unwanted effects:
- Bronchoconstriction
- Cardiac depression
- Fatigue
45
Define efficacy
The maximum response achievable from a drug
46
Define affinity
Degree to which a substance tends to bind with another
47
What is up-regulating in terms of receptors?
An increase in receptors following low levels of its hormone
48
What is down-regulation in terms of receptors?
Decrease in receptors following high levels of a hormone
49
Give an example of how hormones influence receptors for other hormones
- Oestrogen must be present to prime receptors for progesterone in the menstrual cycle
- Thyroid hormone up regulates adrenaline receptors and allow the release of fatty acid from adipose tissue
50
Are hormones agonists or antagonists?
Agonists
51
Give an example of an antagonist used to block a hormone?
Clomiphene citrate is used to block oestrogen - used in IVF
52
What does activation of membrane receptors result in?
- Receptor enzyme activity
- Activity of JAK kinases associated with the receptor
- G proteins coupled to receptors generate the second messenger
53
What does the activation of intercellular receptors cause?
- Transcription of genes
- Change in synthesis of proteins
- Change in rate of protein synthesis
54
Give examples of how large doses of hormones are used as drugs?
- Cortisol to reduce inflammation
| - Progesterone as the morning after pill
55
What coordinates the endocrine system?
Hypothalamus and pituitary gland
56
Name the factors released from the hypothalamus that co ordinate the endocrine system
- Thyrotrophin releasing factor
- Growth hormone releasing factor
- Growth hormone inhibiting factor
- ADH
- Oxytocin
57
Give some characteristics of insulin?
- Peptide home
- Secreted by beta cells of islets of Langerhans
- Inative precursor of proinsulin
- Cleaved by proteolytic enzymes
58
When is insulin released?
- When blood glucose concentration rises above the normal range (70-110mg/dl)
- Increased blood arginine/leucine
59
What are the two types of diabetes mellitus?
- Insulin dependant
| - Non insulin dependant
60
Give the characteristics of insulin dependant diabetes mellitus (type 1)
- Lack of insulin from beta cells
- Cells can't take up glucose so body reacts as if blood glucose is low
- Lipid and proteins broken down which results in ketoacidosis - Death
- High glucose in urine
- Fatigue, muscle wasting. neuropathy
61
Give the characteristics of non-insulin dependant diabetes mellitus (type 2)
- Typically in obese individuals over 40
- Maturity onset diabetes
- 90% of diabetes
- Insulin levels normal but tissues don't respond to it
62
What treatments are available for type 2 diabetes?
- Weight loss
- Metformin - drug which lowers blood sugar, causes glucose uptake by muscles to increase, does not cause hypoglycaemia, causes GI disturbances -side effect
63
What is diabetes insipidus?
Posterior pituitary gland fails to produce enough ADH causing excessive drinking and urination - often confused with diabetes as similar symptoms
64
What is polycystic ovarian syndrome?
- 20% of women have cysts
- 6-10% have polycystic ovarian syndrome
- causes insulin resistance and hyperinsulinemia
- Reduced fertility
65
What hormones does the thyroid gland release?
- Monoiodotryosine
- Diiodotryosine
- Triiodothyronine
- Thyroxine
66
What does the thyroid hormone stimulate?
- Protein synthesis
- Increased use of glucose for ATP production
- Increases lipolysis
67
What happens if there is a thyroid hormone deficiency?
```
Cretinism
- In children
- Congenital hypothyroidism
- Mentally immature, cannot hear or speak
- Bone growth retarded
- Sexually immature
Myxoedema
- Adult hypothyroidism
- Low TSH
- Low cardiac output - oedema
```
68
What happens If there is too much thyroid hormone?
Graves Disease
- more common in females
- Autoimmune disease
- Pressure behind eyes cause exophthalmos
69
What are the three layers of a blood vessel?
- Tunica intima
- Tunica media
- Tunica externa
70
What does the tunica intima consist of?
- Endothelium
| - Basement membrane
71
What does the tunica media consist of?
- Elastic fibres
| - Muscle
72
What does the tunica external consist of?
- Collagen
- Vasa vasorum - making connections with muscle cells in media
- Lymphatics
73
Why does the aorta have lots of elastic tissue?
To cope with the peak ejection pressures
74
What is arteriosclerosis?
Thickening of the arterial walls due to focal calcification
75
What is atherosclerosis?
Lipid and monocyte deposition in the tunica media
- Cholesterol
- Low ApoE
- High LDL's
76
How and why are blood vessel diameters changed?
- Important in maintaining good pressure
- AG11 is a powerful vasoconstrictor
- ACE inhibitors reduce blood pressure
77
Give some characteristics of capillaries
- Just tunica initima - endothelium and basement membrane
- Simplest vessel
- variable structure - leaky/tight
- Role in the formation of tissue fluid
78
Difference between venules and arterioles?
Venules are less muscular than arterioles and are more prone to collapse
79
Differences between veins and arteries
Veins are less muscular, more distensible (can open more) and they can store blood
80
Give some special characteristics of large veins
Vena cava
- Longitudinal bundles of smooth muscle which contract to shorten and widen the vessel
Large veins
- More muscular than venules
- Contain pocket valved to ensure correct direction of blood vessels
81
What is the function of the lymphatic system?
Delivers excess tissue fluid to the cardiovascular system
| Impaired flow leads to oedema - build up of fluid in tissue
82
Give the characteristics of lymphatics?
- Blind-ended, freely permeable
- Flap valves to allow fluid in and out
- Larger lymphatics are vein like - pocket valves
83
What is the role of the lymphatic system in the immune response?
- Lymph nodes move fluid around
| - Wuchereria brancrofti (worm) - lives in lymphatic system in humans
84
What do the maxima and minima of the blood pressure wave formed by the heart show?
Maxima - systolic pressure
Minima - Diastolic pressure
As blood travels through the arteries the maxima and minima pressure close together
85
What are the pressures of the vessels in the pulmonary circuit?
- Systolic - 25mmHg
- Diastolic - 8mmHg
- Capillaries - 10mmHg
86
What are the pressures of the vessels in the systemic circuit?
- Systolic - 120mmHg
- Diastolic - 75mmHg
- Capillary - 15mmHg
87
How do you measure arterial blood pressure?
- Inflatable cuff, release pressure
- First sound is systolic pressure
- Muffling is diastolic
88
What affects systolic pressure?
- Ejection velocity
| - Stroke volume
89
What is diastolic pressure affected by?
- Total peripheral resistance
| - Blood flow from arterial to venous sides
90
How is arterial blood pressure regulated in the short and long term?
Short term - regulated by baroreceptors - all around circuit and feedback information
Long term - control of blood volume
91
Give an example of baroreceptor control?
When lying doen arterial pressures are equal but standing up its not so diastolic pressure increases. In order to raise it
- Increase of sympathetic outflow to the heart- increases cardiac output
- Constricts Flo to vessels to increase resistance
Mean arterial pressure = Cardiac output x resistance
92
Name some treatments for low blood pressure
Increase resistance (by vasoconstriction)
- Angiotensin II
- Phenylephrine (sympathetic agonist at b1 receptors)
Increase cardiac output
- Sympathetic agonist at b1 receptors
- Na/K+ ATPase pump inhibitor
93
Name some treatments for high pressure
Decrease resistance (by vasodilation)
- Prazosin (sympathetic antagonists at a1 receptors
Decrease cardiac output
- Sympathetic antagonists at B1 receptors
-Ca2+ channel blockers
94
How does exercise affect blood pressure?
Diastolic decreases as resistance decreases
| Systolic increases as stroke volume increases
95
What are the two types of respiration?
Internal - glycolysis etc
| External - Ventilation
96
What is essential for efficient diffusion?
Maintaining a short diffusion distance
97
How are the branches of the lungs numbered?
Conducting zone:
The trachea would be a generation 0 and the bronchioles are generation 16.
Respiratory zone:
Alevoii sacs up to generation 23
98
What is present in the conducting zones of the respiratory system?
- Nose
- Oropharynx
- Larynx
- Trachea
- Bronchial tree
99
What is the function of the conducting zone in the respiratory system?
- Filters the air
- Temperature - changes to body temperature
- Humidify - keep the alveoli moist
100
What is the structure of the bronchial wall?
- Reinforced with cartilage (prevent from collapsing)
- Smooth muscle - alter airway diameter
- Mucous gland - line airways
- Elastic tissue - prevent over expansion of airways
101
What types of epithelium are present in the respiratory system?
- Ciliated epithelia - wast mucus up the airways
- Goblet cells - produce the mucus
- Sensory nerve endings - detection - cause coughing
102
What is the structure if the bronchioles?
- Lack of cartilage support
- Lined by respiratory epithelium
- More smooth muscle
- Less than 1mm diameter
103
What is the structure of the alveoli?
- Large surface area
- Thin wall - rapid diffusion of blood
- Fed from terminal bronchiole
104
What is the air blood barrier?
For gas to exchange multiple barriers have to be crossed
Created by a flattened cytoplasm of a type 1 pnemuocyte (type 2 produces surfactant) and the capillary wall
Large surface area for gas exchange
105
What are the two processes of ventilation?
- Inspiration
| - Expiration
106
Describe the mechanism of quite (at rest) inspiration?
- involves the primary muscle of inspiration
- Diaphragm contract and moves down increasing the volume of the thorax
- Intercostal muscles contract - Ribs up and out - increases volume
- Pressure in the thorax falls below atmospheric pressure causing air to move in
107
What is the mechanism of forced inspiration?
- Primary and accessory muscles of inspiration are used
- Scalenes - moves ribs up
- Sternocleidomastoids - moves sternum up
- Neck and back muscles
- Upper respiratory tract muscles
108
Describe the mechanism of quite (at rest) expiration?
- No primary muscle of expiration - passive process using elastic recoil
- External intercostal muscles
- Recoil of the lungs
- Diaphragm relaxes
109
Describe the mechanism of forced expiration?
- Active process
- Accessory muscles
- Internal intercostals contract - help reduce thorax size
- Neck and back muscles
- Abdominal muscles - push diaphragm down
110
What is the function of the pleural cavity?
- Pleural cavity filled with secretions
- Prevents lungs from sticking to the chest wall
- Enables free expansion and collapse of the lungs
111
What is the pressure in the intraplural space sub atmospheric?
The elastic nature of the lungs would cause them to collapse inwards
The cages wall would expand
At rest these forces balance meaning the pressure in the intraplural space is sub atmospheric
112
How does a lung collapse?
Breach of the chest wall would cause air to enter the intrapleural space meaning the pressure would fall to the same as atmospheric
Lung would collapse to minimum volume due to its elastic nature
113
What is compliance and how is it measured?
The measure of elasticity - the ease with which the lungs and thorax expand during pressure changes
C = change in volume/ change in pressure
114
What does a low and a high compliance imply?
Low compliance - more work requires to inspire e.g. pulmonary fibrosis
High compliance - more difficulty in expiring dues to loss of elastic recoil e.g. emphysema
115
What are the two major components involved in the elastic recoil of the lungs?
- Anatomical component - elastic nature of cells and extracellular matrix
- Surface tension generated at air fluid interface
116
How is a surface tension developed in the lungs?
Due to its polar nature, water molecules adhere together, giving rise to surface tension at air - water interfaces
117
What is Laplace's equation?
P = 2T/r
| Pressure calculated by the surface tension and the rains of the aveoli
118
What does Laplace's equation tell us about alveoli?
That the pressure in the larger alveoli is lower than that in the small alveoli meaning that air will move out of the small and into the large causing their collapse
119
How is the collapse of small alveoli overcome?
By the use of surfactant as it reduces the surface tension
120
What is the function of surfactant and how is it produced?
Produced by type II pneumocytes and is composed of lipids and proteins
It reduces the surface tension of small alveoli stopping them from collapse
It also slows the rate of inflation of the alveoli
121
What is used to measure lung volumes?
A spirometer
122
What is the difference between anatomical and physiological dead space?
- Anatomical is the volume of conducting airways
- Physiological is the volume of lungs not participating in gas exchange
Two values are usually almost identical
123
What is the residual volume?
Volume of air left in lungs after you've breathed out as much as possible
124
What is the vital capacity?
Total volume of air that can possibly be breathed in and out
125
What is the total capacity?
Sum of the residual volume and vital capacity
126
What is tidal volume?
Volume of air breathed in and out at rest
127
How do reserve volumes change during exercise?
- Tidal volume increases
| - Reserve volumes go down
128
How is residual volume calculated?
Helium dilution technique
- Known vol and conc in chamber \
- Diluted as breathes
129
What is the relationship between flow of air in or out of the lungs and the pressure gradient?
They are directly proportional
130
What is the relationship between flow of air in or out of the lungs and the resistance?
Inversely proportional
131
What is Poiseuilles's law?
- Airway resistance is proportional to gas viscosity and the length of the tube but is inversely proportional to the fourth power of the radius
- Small changes in airway diameter have a big impact on the resistance and hence the flow rate
- R ∝ 1/(r^4)
132
What is the total airway resistance in a normal individual?
1.5cm H2O.s.litres^-1
133
What factors increase airway resistance?
- Increased mucus
- Oedema
- Airway collapse
134
How does increased mucus impact the airway resistance?
Increased mucus secretion will reduce airway diameter
135
How does an oedema impact the airway resistance?
Increased fluid retention in the lug tissue will cause swelling and narrowing of the airways - increased resistance
136
How does the collapse of the airway impact the airways resistance?
In forced expiration, airways narrow causing resistance
137
How does the autonomic nervous system control the bronchial smooth muscle?
Parasympathetic
- ACh released from Vagus nerve acting on muscarinic receptors leasing to constriction
Sympathetic
- Release of norepinephrine from nerves leads to dilation
138
What humeral factors control the bronchial smooth muscle?
- Epinephrine leads to dilation
| - Histamine released during inflammatory response leads to constriction
139
What is the relationship between lung ventilation and lung perfusion?
Ratio = V/Q
140
What is lung perfusion and where is it greater?
The passage of fluid through the circulatory system
| Greater at the base than the apex
141
How can the ratio between lung ventilation and lung perfusion be used clinically?
Can be compared against the produced volume to identify problems with gas exchange
142
What is Daltons law?
The total pressure of a mixture of gases is the sum of their individual partial pressures
143
What is standard atmospheric pressure?
760mmHg
144
What is Henry's law and what is it used for?
To calculate the concentration of a gas dissolved in a solution
[Gas}dis = Solubility x Partial Pressure
145
Why is haemoglobin required?
Because the body requires 250ml O2/min but Oxygen has a low solubility in saline so at rest the plasma would be able to carry 15ml O2/min at the most. This is not sufficient for life
146
Give the structure of haemoglobin?
- Tetrameric structure
- Four subunits
- Molecular weight of 68kD
- 2 alpha and 2 beta chains
147
How is does iron bind to haem?
The enzyme methaemoglobin reductase converts Fe3+ to Fe2+ because for it to bind it has to be in Fe2+ state
148
What is the tense state ad relaxed state of haemoglobin?
Tense state - low affinity for O2
| Relaxed state - high affinity for O2
149
Why is there a lag at the start of the haemoglobin dissociating curve?
Because haemoglobin starts in its tense state meaning it has. allow affinity for oxygen. Once one oxygen molecule has bound then the haemoglobin state relaxed meaning it has a high affinity for oxygen
150
How does temperature affect the oxygen - haemoglobin dissociation curve?
At a low temperature, haemoglobin has a higher affinity for oxygen so the curve shifts to the left. At high temperature, the curve shifts to the right - oxygen will dissociate earlier
151
What is the affect of PH on the oxygen - haemoglobin dissociation curve?
CO2 is n acidic gas so when the PH is lowered the curve shifts to the right so that oxygen dissociates easier so CO2 can bind
152
What is the effect of 2,3 diphosphoglycerate on the oxygen - haemoglobin dissociation curve?
It binds to the B chain of haemoglobin causing the curve to shift to the right as oxygen can't bind
153
What is the benefit of increased temperature, PH and 2,3 phosphoglycerate cause a right shift in the dissociation curve?
Respiring tissues cause these factors to increase meaning that the dissociation of oxygen occurs and the oxygen is released into the tissues
154
Does fatal haemoglobin have a low or high affinity for oxygen in comparison to normal haemoglobin and why?
Has a higher affinity for oxygen because the beta chains are replaced with delta chains meaning that 2,3 - phosphoglycerate cannot bind
155
What are the methods of CO2 carriage in the blood?
Carried as
- dissolved carbon dioxide
- carbonic acid
- biocarbonate
- carbonate
- carbamino compounds
156
What are channels are used by CO2 to enter a red blood cell?
- Aquaporins
| - Rhesus complex
157
What happens to CO2 in the red blood cell?
Co2 is converted into HCO3- with the help of the enzyme carbonic anhydrase
158
What are the two categories of lung disease?
Obstructive
- Reduction in flow through airways
Restrictive
- Reduction in long expansion
159
What is obstructive lung disease?
```
Narrowing of the airways due to
- Excess secretions
- Bronchoconstriction - asthma
- Inflammation
causes an increase in airflow resistance
```
160
What test could be used to test for an obstructive lung disease?
If forced expiratory volume on a spirometer drops below 80% than obstructive lung disease
161
In a volume - time curve, what shape would the trace of an obstructive and restrictive lung disease patients be?
Obstructive would take longer but would eventually reach the full capacity
Restrictive would not reach the full capacity
http://www.nataliescasebook.com/tag/spirometry
162
In flow - volume loops what shape would an obstructive lung disease be?
Would curve inwards slightly causing a concave shape
http://www.sharinginhealth.ca
/imaging/pulmonary_function_tests.html
163
Name some obstructive diseases?
- Chronic bronchitis
- Asthma
- COPD
- Emphysema
164
What can trigger an asthma attack?
```
Atopic (extrinsic)
-allergies
- contact with inhaled allergens
Non-atopic (intrinsic)
- Respiratory infections
- Cold air
- Stress
- Exercise
```
165
What happens during an asthma attack?
- Movement of inflammatory cells into the airways
- Release of inflammatory mediators such as histamine
- causing bronchoconstriction
166
What are the treatments of asthma?
- Salbutamol inhaler - B2 adrenoreceptor agonists causes dilation of airways
- Glucocorticoids (steroid inhalers) used to reduce inflammatory responses
167
What are the causes restrictive lung diseases?
```
Reduced chest expansion
- Chest wall abnormalities
- Muscles contraction deficiencies
Loss of compliance
- Normal ageing process
- Increase in collagen
- Exposure to environmental factors
```
168
What does asbestosis do to the respiratory system?
Slow build-up of fibrous tissue leading to a loss of compliance (elasticity)
169
How can you diagnose a restrictive lung disease?
Patients vital capacity is reduced below the expected
170
What part of the brain controls respiration?
Medulla
171
What is the role of dorsal respiratory group (DRG) in the control of respiration?
Controls inspiration by sending signals to the inspiratory muscles
spontaneously active
172
What is the role of ventral respiratory group (VRG) in the control of respiration?
Controls inspiration and expiration
| Inactive during quiet respiration
173
What centres in the pons are involved in the regulation of breathing?
Pneumotaxic centre
- Increases the rate by shortening inspirations- inhibitory effect on inspiratory centre
Apneustic centre
- increases the depth and reduces the rate by prolonging inspirations -stimulates inspiratory centre
174
What is the role of stretch receptors in regulating breathing?
- Negative feedback loop
| - When diaphragm contracts it stimulates the stretch receptors and inhibits respiration
175
What is the role of central chemoreceptors?
Monitors conditions in the cobra-spinal fluid
| If rise in CO2 then stimulates an increase in ventilation
176
What is the role of peripheral chemoreceptors?
Located in carotid body
Respond to and increase in CO2, PH and O2
Stimulation leads to an increase in ventilation
177
What is the average total body water content?
60% of a persons body weight
| - For an average weight of 70Kg then there would be 42L
178
How much of the fluid is intercellular and extracellular?
```
Intracellular
- 20-35 litres
Extracellular
- interstitial - 11-12 litres
- Plasma - 3-4 litres
- Transcellular - 1.5-2
```
179
What is the difference in the distribution of cations in and outside a cell?
- K+ in side the cell (148mm) compared to outside the cell (5mm). Means that that K+ will move out of the ell when channels open - regulate membrane potential
- Na+ is low inside the cell (10mm) and high out (140mm) - Produce action potentials
180
What is the difference in the distribution of anions in and outside a cell?
- Cl is low inside (4mm) and high outside the cell (103mm)
| - Proteins 55mm inside the cell and 15mm out
181
What is the average daily input of sodium per day and how is it excreted?
150mmoles a day
| Excreted 140mm through urine and 10mm through sweat
182
What is the average daily input of water per day and how is it excreted?
```
Daily input 2.6L
- drink 1.2L
- food 1L
- metabolism - 0.35L
Excreted
- urine 1.5L
- sweat 1.1L
```
183
Where in the body is the kidney found and how much does it weigh?
- Between the 12th thoracic and the 3rd lumbar
| - Weights about 150g
184
Name some of the general structures on the outside of a kidney
- Adrenal gland sits on top
- Ureter
- Renal vein overlapping the renal artery
- Abdominal artery
- Suprarenal artery and vein
185
Name some congenital abnormalities of the kidneys
```
Renal agenesis
- leads to miscarriage
- 1 in 2500 foetuses
Ectopic kidney
- Found in an unusual location (e.g. pelvis)
- Increased risk of kidney stone
Horseshoe kidney
- 2 kidneys are fused into 1 in horseshoe shape
- Kidney stones
```
186
What is the structure of a longitudinal sections of a kidney?
Ureter goes to the pelvis
pelvis fans out into calyx and papilla
Cortex surrounds the papilla and is enclosed by the capsule
http://www.gentamicin.com/symptoms/kidney-damage
187
What is the function of the nephron?
Determines what is excreted and how much
188
How many nephrons are there per kidney?
1-1.5 million
189
What is the structure of the nephron?
- Collecting duct
- Distal tube
- Bowmans capsule
- Loop of Henle
- Proximal tubule
190
What is the main function of the Bowman's capsule?
Ultrafiltration
191
What are the two types of nephron and the difference between the two?
- Superficial nephron - 85%
| - Juxtamedullary nephron - 15%
192
Define renal failure?
Defined as a fall in glomerular filtrate - leads to an increase in serum urea an creatinine
193
What are the differences between acute and chronic renal failure?
```
Acute
- Reversible
- Normal haemoglobin level
- Normal renal size
- No peripheral nerve damage
Chronic
- Irreversible
- Decrease in haemoglobin levels
- Decrease in renal size
- Peripheral nerve damage
```
194
How does renal failure progress?
- The glomerular membrane thickens
- Damage the glomeruli causing scarring
- This causes interstitial inflammation and fibrosis
- Reduction in renal size
- Causes uraemia
195
What is uraemia?
A build up of urea and other nitrogenous waste compounds in the blood
196
How cam you tell on an ultrasound that somebody has renal failure?
Kidney looks smaller and brighter
197
What are the symptoms of renal failure?
```
Failure to excrete salt and water
- Hypertension
- Hyperkalaemia (high K+)
- Mild acidosis
Poor excretion of urea and creatinine
- Anorexia
- Nausea
- Vomiting
Leak of protein into urine
Failure production of erythropoetin
- Less red blood cells produced
Failure to excrete PO4 2-
- Metastatic calcification - calcium phosphate formed forming a precipitate - itch
- Bone disease
```
198
What are the stages of renal failure?
- Mild renal - GFR>75
- Mild - GFR 50-75 - Early bone disease
- Moderate GFR 25-50 - Anaemia
- Severe GFR 10-25 - Salt and water retention
- End stage GFR <5-10 - Dialysis
199
What are the causes of renal failure?
- Glomerulonephritis - 30%
- Hypertension - 10%
- Diabetes melitus - 25%
- Polycystic kidney disease - 20%
- Unknown - 10%
200
What treatments are available for renal failure?
- Diet - restrict protein water and salt intake
- Phosphate binders - reduce PO42- levels
- Sodium Bicarbonate - reverse acidosis
- Diuretics - Na retention
- Dialysis
- Transplant
201
Where does filtration take place?
Occurs in the glomerular capillaries and moves into Bowman's capsule snd moves along the nephron
202
Where does the the blood and fluid that is not passed into the Bowman's capsule go?
The efferent arteriole back into the capillaries
203
What are the two processes involved in the formation of urine?
Filtration and reabsorption
204
What is present in glomerular filtrate?
20% of plasma is removed and is filtered. H20 and other small molecules are filtered out but blood cels and proteins are restricted
205
Is there protein present in the urine?
No - 1% protein found in glomerular filtrate as it has a small molecular weight but is usually reabsorbed in the proemial tubule.
If urine present in the urine - suggests renal failure
206
What is transcellular reabsorption?
Move from lumen of the tubule across the epithelium to the capillary
207
What is transcellular secretion?
Move from the capillary across the epithelium to the lumen of the tubule
208
What is paracellular secretion or reabsorption?
Fluid moves in between epithelium cells through tight junctions
209
What is the role of the proximal tubule?
Bulk reabsorption of 70% of the glomerular filtrate
- 70% of water and Na+
- 100% of glucose and amino acid
- 90 % HCO3-
210
What are the apical and basolateral membranes?
Apical is the side go the lumen of the tubule
| Basolateral is the side of the capillaries
211
How is glucose reabsorbed in the proximal tubule?
- Na+-K+ pump on the basolateral membrane creates a negative sodium gradient by pumping out 3Na+ and bringing in 2K+
- Na+ - glucose co transporter on the apical membrane moves Na+ and glucose in
- Glucose diffuses out the basolateral membrane into the capillary
- Net reabsorption of glucose and Na+
212
How are amino acids reabsorbed in the proximal tubule?
- Na+-K+ pump on the basolateral membrane creates a negative sodium gradient by pumping out 3Na+ and bringing in 2K+
- Na+ - amino acid co transporter on the apical membrane moves Na+ and amino acids in
- Amino acids diffuses out the basolateral membrane into the capillary
- Net reabsorption of AA and Na+
213
How are PO42- ions reabsorbed in the proximal tubule?
- Na+-K+ pump on the basolateral membrane creates a negative sodium gradient by pumping out 3Na+ and bringing in 2K+
- Na+ -PO42- co transporter (NaPiII) on the apical membrane moves Na+ and PO42- in
- PO42- diffuses out the basolateral membrane into the capillary
- Net reabsorption of PO42- and Na+
214
How is water reabsorbed in the proximal tubule?
Through paracellular reabsorption - between cells through tight junctions
215
What is the phenotype of NaPiII knockout mice?
```
Young mice:
- 1.65mm reabsorbed compared to 2.1mm
- Abnormal skeletal development - bones less dense
Adult mice
- Show compensation
```
216
What are the Na+-Glucose co transporters used in the proximal tubule?
SGLT1
SGLT2
- 14 transmembrane domains
217
What is familial renal glycosuria?
A mutation SGLT2
Causes only a few grams of glucose to be reabsorbed so high glucose conc in urine
Autosomal recessive
Carriers have mild effects
218
How is HCO3- reabsorbed in the proximal tubule?
- Na+-H+ exchanger on the apical membrane moves Na+ in and H+ out
- H+ binds with HCO3- forming H2CO3
- Using carbonic anhydrase it splits into CO2 and water
- Water moves through aquaporins and CO2 diffuses in
- CO2 and H2) join back together in the cell and split into H+ which is recycled and HCO3- diffuses out of the basolateral membrane
- Net reabsorption of HCO3-
219
What is the phenotype of Na+-H+ exchanger knockout mice?
- HCO3- is not reabsorbed as much
- Plasma pH drops from 7.33 to 7.27
- Acidosis
- Blood pressure drops due to the fall in fluid reabsorption (extracellular fluid volume decreases)
220
Why is there a renal transport maximum and what is it?
- Because the reabsorption of substance mainly require carriers and there are a limited number of carriers that can be in the cell membrane
- 300mg of glucose per 100ml of plasma
221
Why does the dose of penicillin have to be higher than actually required?
Because some will be quickly removed by the proximal tubule
222
What is the function of the loop of Henle?
Reabsorbs Na+, Cl-, H20, Ca2+ and Mg2+
Decides the concentration of urine
Site of action of loop diuretics
223
What is the structure of the loop of Henle?
- Thick ascending limb
- Thin ascending limb
- Thin descending limb
224
What is reabsorbed in the thick ascending limb?
- Na+
- Cl-
- Ca2+ and Mg2+
225
How is Na+ and Cl- reabsorbed in the thick ascending limb?
- Na+-K+ pump on basolateral membrane creates a Na+ gradient by pumping 3Na+ out and 2K+ in
- NKCC2 (Na+-K+-2Cl- co transporter 2) moves them into the cell
- Cl- moves out of the basolateral membrane through CLCK channels activated by Barttin
- K+ is recycled on the apical membrane through ROMK channel
- Na+ moves out of the basolateral membrane through the Na+-K+ pump
226
How is Ca2+ and Mg2+ reabsorbed in the thick ascending limb?
The net reabsorption of Na+ drives Ca2+ and Mg2+ in-between the cells (paracellular reabsorption)
227
What are the symptoms of Bartter's syndrome?
- Hypotension
- Hypokalaemia (low K+) (problem with thick ascending limb)
- Metabolic alkalosis
- Hypercalciuria (high Ca2+ in urine)
- Kidney stones
228
What causes Bartter's syndrome?
- Recessive genetic disorder
- ROMK mutation?
- Na+ and Cl- not reabsorbed
- Ca2+ and Mg 2+ not reabsorbed
229
What is the phenotype of ROMK knockout mice?
- Fractional excretion (amount of urine/amount filtered) is usually less than 1% but in knockout mice increase to 4-7%
- Show acidosis
- Salt wasting
- Polyuria (large amount of urine)
230
Name some loop diuretics and explain how they work?
Furosemide and Bumetanide
- Blocks NKCC2 and stops the reabsorption of Na+ and Cl-
- Stops hypertension
- Risks kidney stones
231
What is reabsorbed in the early distal tubule?
Na+, Cl- and Mg2+
232
How is Na+ and Cl- reabsorbed in the early distal tubule?
- Na+-K+ pump on basolateral membrane creates a Na+ gradient by pumping 3Na+ out and 2K+ in
- NCC (Na+-Cl- transporter) pumps them in
- Cl- moves through basolateral membrane through CLCK channel activated by Barttin
- Na+ pumped out by Na+-K+ pump
233
How is Mg2+ reabsorbed in the early distal tubule?
Using a Mg2+ transporter on apical membrane - unknown what
234
What are the symptoms of Gitelman's syndrome?
- Hypotension
- Hypokalaemia
- Metabolic alkalosis
- Hypocalciuria (low calcium in urine ) -DIFFERENT TO BARTTERS SYBDROME
235
What causes Gitelman's syndrome?
- Autosomal recessive
| - mutation in the NCC channel
236
What happens in an xenopus oocyte that is injected with RNA encoding for mutated NCC channel?
Less NCC then there should be
| Also not many NCC channels actually present on the apical membrane - trafficking mutation
237
What are thiazide diuretics (chlorothiazide) used for?
- Treat high blood pressure
| - Side effects resemble Gitelman's symptoms
238
What advantage does being a carrier for a mutant ROMK, NCC or NKCC2 have?
Protects against hypertension later in life
239
What is the function of the late distal and collecting duct?
- Reabsorption of Na+ and H2O
| - Secretion of K+ and H+
240
What are the two cell types in the late distal and in the cortical collecting duct?
```
Principle
- Na+ and H20 reabsorption
- K+ and H+ secretion
Intercalated
- alpha IC and beta IC
- H+ secretion and absorption
- HCO3- secretion and absorption
```
241
How is Na+ and H2O reabsorbed in a principle cell?
- Na+-K+ pump on basolateral membrane creates a Na+ gradient by pumping 3Na+ out and 2K+ in
- Na+ moved in through an ENaC channel on apical membrane
- H20 moves in through aquaporin 2 on apical membrane and out through aquaporin 3 and 4 on basolateral
242
What is the fate of K+ in a principle cell?
- ROMK channel on apical membrane and Kir2,3 channel on basolateral membrane both pump K+ out
- The more Na+ secreted out of the Na+-K+ pump then the more K+ brought into the cell an therefore more secreted
243
What is the function of amiloride and how does it work?
- Reduces blood pressure
- Blocks ENaC channels stopping the reabsorption of Na+ in the principle cell
- This decreases the secretion of K+
244
What is the role of alpha interlaced cells?
- When diet high in protein, acid is high so needs to be secreted
- HCO3- is pumped out of the basolateral membrane and Cl- in through AE1 exchanger
- Cl_ is pumped out again and is recycled
- H+ is secreted out of the apical membrane using ATP
245
What happens if another HCO3- Cl- exchanger is placed on the apical membrane in an alpha intercalated cell?
HCO3- is secreted to tubular fluid
| Gain of function mutation
246
What is the function of a beta intercalated cell?
Reduces PH
- HCO3- Cl- changer on apical membrane secreting HCO3-
- H+ pumped into capillary across basolateral
247
What causes acute renal failure?
- Fall in glomerular filtarte
- impaired fluid and electrolyte homeostasis
- Accumulation nitrogenous waste
- High K+
- Rhabdomyolysis
248
How can you treat acute renal failure?
Dialysis
| Transplant
249
What are the symptoms of acute renal failure?
- Hypervolaemia
- Hyperkalaemia
- Cardiac excitability
- Acidosis
- High urea
250
What hormones are involved in body fluid homeostasis?
- Vasopressin (ADH)
- Aldosterone
- Renin angiotensin
251
What is the function of vasopressin?
Conserves H2O
| - High vasopressin means high body fluid osmolality
252
Where is vasopressin manufactured and how is it released?
- Manufactured in the hypothalamus
- Released from the posterior pituitary gland
- Action potential fired from hypothalamus to pituitary gland causing its release into the interstitial fluid and into the general circulation
253
What is the role of hypothalamic osmoreceptors?
Detects a change in osmolality by +- 3mosmol/Kg
| Causes the release of vasopressin and feeling of thirst
254
How does ecstasy kill you (in relation to vasopressin)?
It causes the release of vasopressin so if you drink to much then it will cause swelling on the brain
255
What affect does alcohol have on vasopressin?
Causes a decrease in vasopressin - need to urinate often and causes dehydration - starts the process of dehydration
256
What is the principle cell model?
The idea that vasopressin causes the insertion of aquaporin 2 channels into the apical membrane of the principle cell. Aquaporin 3 and 4 on the basolateral membrane are not regulated by vasopressin meaning net increase in reabsorption of water
257
What is the difference between central diabetes insipidus and nephrogenic diabetes insipidus?
Central - Hypothalamus does not stimulate the release of vasopressin, can be treated by a nasal spray containing vasopressin
Nephrogenic - There is no response to the released vasopressin - defect in receptor, no treatment
258
Where is aldosterone released from?
Adrenal cortex
259
What is the role of aldosterone?
Regulates plasma Na+, K+ and body fluid volume
Released in response to an increase in plasma K+, Na+ and ECF volume
Acts on distal tubule and collecting duct
260
How is plasma Na+ regulated?
Partly by aldosterone but mainly by vasopressin because of its effect on water
261
How does aldosterone work?
It moves inside the principle cell and alpha intercalating cell to their nucleus and stimulates the protein synthesis of membrane carriers for K+, H+ secretion and Na+ reabsorption
262
What is Liddle's syndrome?
- Hypertension caused by high Na+ reabsorption
- Low aldosterone
High number of ENaC channels because once in apical membrane they cannot be removed
263
What is Pseudohypoaldosteronism?
- Salt loss through urine
- high aldosterone
- Response to aldosterone has been lost
- Low blood pressure
264
What is the role of Renin-angiotenisn?
Regulates body fluid volume, plasma Na+, K+
265
Where is Renin-angiotensin released from?
Released from juxtaglomerular apparatus (JGA)
266
What is the Renin-angiotensin cascade?
- If there is a decrease in extracellular fluid, Renin-angiotensin released
- Converted from angiotensinogen to angiotensin 1
- Then to angiotensin II using ACE enzyme
- Occurs in capliarries
267
What is the role of Angiotensin II?
Stimulates the adrenal gland to release aldosterone so increases plasma Na+ and ECFV
Also causes vasoconstriction in arteries causing an increase in blood pressure
268
What problems can be associated with the Renin-angiotensin system?
ACE enzyme can cause high blood pressure
| - Can use ACE inhibitors to reduce blood pressure
269
Will the body prioritise extracellular fluid volume of osmolality?
Extracellular fluid volume
| - Aldosterone system overpowers vasopressin
270
Where does fertilisation occur?
In the ampulla of the female reproductive tract
271
How is diversity maintained in fertilisation?
- Provides half chromosomes from each parent
- Randomly selects which paternal chromosome enters gamete
- Exchange of genetic information during gametogenesis
272
How does the pill work?
By thickening the lingo of the mucus stopping sperm from getting through
273
What does capacitate mean in terms of sperm?
Sperm must capacitate in the female tract (requiring cells from the mucus) in order to fertilise the egg
274
What happens during capacitating a sperm?
- Acrosome reaction - Acrosomal cap can break down to reveal receptors on the head of the sperm
- Motility changes - Become hyper motile - swim around quickly and then stop and repeat
275
When does meiosis occur in eggs?
Complete first stage after fertilisation before born and second stage when the egg is ovulated
276
Where are gametes formed?
In gonads
277
Does the male or female decide the sex of the baby?
Male as their gametes have either 22 chromosomes and an x or a y
278
When is the sex of an offspring decided?
At conception
279
When does a female phenotype develop?
If ovaries present or no gonads present
280
When does a male phenotype develop?
If testes are present
281
What are gonadal ridges?
Where gonads develop
| Gonadal ridges form on the posterior abdominal wall within a few weeks of fertilisation
282
What are primordial gem cells?
Primitive germ cells present in gonadal ridges
Look similar in males and females until further development
Occurs about 5 weeks after
283
What is an oogonia?
A primitive oocyte
| Millions after 7 moths of development
284
Why does the number of oogonia in developing female fall?
Number falls as oogonia degenerate due to less FSH and they are converted into oocytes using meiosis inducing substance (MIS)
285
What is the role of meiosis inducing substance (MIS) in males and females?
Females:
- Causes the change for oogonia to oocutes - meiotic transfer
Males:
Testis release meiosis preventing substance which overpowers MIS until puberty when testis develop into testes
286
What are seminiferous tubules?
Produce sperm through life
Formed from testis cords
Surrounded by myoid cells
They're coiled
287
What induces testes formation?
- Sry gene induces testes formation
- Testes produce anti - mullein hormone and testosterone
- Product of SRY gene triggers Sertoli cell fate
- If SRY is absent then a Follicle cell develops instead
288
What is the role of SOX9?
Involved in long term maintenance of Sertoli cells and levels increase a few days after SRY is activated in males
SOX9 levels in females decline
Mutations in SOX9 can cause male-female sex reversal
289
What are the supporting cells and connective tissue for male and female gonads?
```
Male
- Sertoli cell
- Testicular cords
Female
- Follicle cell
- Stroma cell
All essential for fertility
```
290
What does a deficiency of 5 alpha reductase do?
- Enzyme converts testosterone to active 5DHT
| - If lacking, male genitalia do not differentiate properly
291
What is testicular feminisation syndrome?
- Genetically male - XY
- Phenotype female
- Low levels of cytosolic carrier that carries testosterone meaning hormone doesn't cause expression
- Female phenotype as there is unopposed action of small amounts of oestrogen
292
How is gender legally assigned?
Presence of recognisable external genitalia
| Will lead to the assignment of gender roles
293
Why are the testes external to the urethra?
So it is at a lower temperature for sperm production
294
What are the three male sex glands?
Prostate, seminal vesicles ad bulbo-urethral glands
295
How many layers do the testes push through?
Push through 5 layers
Layers are slightly displaced so there isn't a continuous hole
Most common place for a hernia
296
What are the characteristics of Sertoli cells?
- Simple columnar epithelium cells
- Non-proliferative
- Provide nutritional and mechanical support to germ cells
- Secretory
- Sensitive to FSH
- Phagocytic
- Not sperm until detach for Sertoli cells - spermatids
297
What are Leydig cells?
Polyhedral cells in connective tissue between seminiferous tubules
Produces testosterone under influence of LH
298
What factors influence testicular formation?
Heat, age, Irradiation, vasectomy
299
What is the pH of sprerm?
7.35-7.5 as urine is acid so it neutralises it
300
What does ejaculate consist of?
- Sailproteins (pre- ejaculate)
- Acid phosphatase
- Sperm
- Fructose
- high K+
- Prostaglandis
301
What is the volume of semen?
3.4+- 1.6mls
302
What are the parts of the female reproductive tracts?
- Ovary
- Fallopian tubes
- Uterus
- Cervix and vagina
303
What is the shape of the cervix?
Round when never given birth
| Flat wen given birth
304
What is the uterus of the lining?
Endometrium - lining of the uterus - selective to oestrogen and progesterone
305
What is an ectopic pregnancy?
When the embryo implants in the Fallopian tube
| Wall of tube is too thin so embryo ruptures and the wall rips - could be fatal
306
Where in the uterus does the embryo implant?
upper posterior side
| If implanted at the bottom of uterus, placenta will grow across the cervix and a c section will be required
307
What is the role of HCG?
Takes over the role of progesterone when pregnant
| If levels aren't high enough than a miscarriage will occur
308
What happens to the remaining oocytes that are not ovulated?
Undergo atresia, a natural process of cell death that destroys follicles
309
What is polycystic ovarian disease?
When many small follicles develop instead of one dominant one
310
What does LH stimulate?
Final stages of follicle maturation
Corpus lutem formation
Ovulation
311
What does FSH do?
Stimulates the maturation of follicles
312
Where are receptors for LH found?
Leydig cells
313
What characterises puberty?
Changes in
- Reproductive organs
- Secondary sex characteristics
- Body size and shape
- Physiological functions such as the way you think, and changes in voice
314
What happens in puberty?
- Become sexually mature
- Become sexually dimorphic
- Have functional gametes
- Secondary sex characteristics become conspicuous
315
What is precocious puberty?
When pubic hair appears before 6-8 years in girls and before 9 in boys
316
What causes precocious puberty?
- Tumour in pituitary
- Meningitis
- Thyroid disorder
- Inherited
317
When is puberty classed as delayed?
Boys
- No pubic hair by age 15
- No sign of descended testes by age 14
- More than 5 years since start of puberty
Girls
- No pubic hair by age 14
- No sign of breast development by age 14
- No menarche by age 16
- More than 5 years since start of puberty
318
What are the possible causes of delayed puberty?
- GPR54 gene - inherited
- Chronic illness - diabetes
- Eating disorders
- Excessive exercise
- Polycystic ovarian syndrome (PCOS)
- Tumours
- Androgen insensitivity syndrome
319
What are the functions of the skeletal muscle?
- Produce movement of body parts
- Support soft tissue
- Maintain posture and body position
- Communication
- Control of openings and passageways
- Maintain body temperature
320
What are the universal characteristics of muscles?
- Excitable - capable of responding to chemical signals
- Conductivity - carry the wave of excitation
- Contractable - shorten
- Extensible -stretch
- Elasticity - return to original shape
321
What is the structure of skeletal muscle (many fibres)?
Skeletal muscle fibre is wrapped in endomysium
Bundle od muscle fibres (muscle fascicle) is wrapped in perimysium
Bundles of muscle fascicles are wrapped in epimysium (blood vessels and nerves also present)
322
What part of he muscle cell carries the contractile activity?
Myofibrils
323
What is the sarcomere?
The contractile unit of the muscle fibre
324
What are the dark and light bands made of in the sarcomere?
Dark bands - myosin
| Light bands - actin
325
How is the depolymerisation of tin prevented in a muscle fibre?
The two ends are capped by a protein
Plus end - alpha actinin
Minus end - tropmodulin
326
What is the role of nebulin in muscle fibres?
Protein made of repeated units that provides a binding site for actin. Ensures that all thin filaments are the same length 'Molecular ruler"
327
How is myosin arranged in a muscle fibre?
```
It is the thick filament
Two domains (head and tail) are in opposite directions on each side of filament to allow contraction (moves actin filaments closer together)
```
328
What is the role of titin in muscle fibre?
Protein made of repeated filaments - largest protein body
| Allows filaments to stretch and recoil
329
What is the mechanism of muscle contraction?
- ATP binds to myosin head causing its dissociation from actin
- ATP is hydrolysed and the phosphate remains attached to phosphate moving head into resting position
- Myosin head, in its new position, binds to actin
- The phosphate attached to the myosin head is released (power stroke) moving actin filament with it
330
How is muscle contraction initiated?
At a neuromuscular junction:
- Action potential activates Ca2+ gated channels
- Triggers the entry of calcium
- Release of ACh from presynaptic neurone across synapse
- ACh binds to its receptor which triggers entry of Na+
- Triggers the release of Ca2+ from the sarcoplasmic reticulum
- Muscle contraction
331
How does the release of Ca2+ trigger a muscle contraction?
- The myosin heads are covered by tropomyosin in a muscle fibre at rest
- Ca2+ binds to troponin on muscle fibre causing a conformational change
- This cause tropomyosin to move unmasking the myosin binding site
332
How does Botulinum toxin affect skeletal muscle contraction?
Most common form of food poising
- Blocks the release of ACh
- Causes muscle weakness and paralysis
- Can be fatal
333
What are the clinical use of botulinum toxin?
Treatment of many illness where you have uncontrolled muscle contraction
- Treatment of strabismus
- Botox
334
Are all skeletal muscles equal in energy consumption?
No
- Slow fibres - lots of mitochondria, aerobic
- Fast glycolytic - appear white but are anaerobic high glycogen content
- Fast oxidative - most mitochondria
335
What are the differences in length of contraction between fast and slow fibres?
```
Fast
- Responds quickly (10msec)
- Contraction cannot be sustained
- e.g. eye muscle
Slow
- Responds slower
- Can be sustained
```
336
How do muscles produce their ATP?
- Oxidative - Oxadative phosphorylation
| - Glycolytic - Glycolysis - produces lactic acid
337
What does lactic acid do?
Lowers the pH of muscle fibre
| Cause fatigue - poisoning of muscle fibre and causes inability to contract
338
What is the role of phosphocreatine in exercise?
- The change of phosphocreatine to creatine using creatine kinase produces ATP
339
What are the functions of the skin?
- Largets organ in the body
- Protection
- Temperature maintenance
- Synthesis and storage of nutrient
- Sensory reception
- Excretion and secretion
340
What are the three layer of the skin?
Epidermis
Dermis
Hypodermis
341
What are the accessory structures of the skin?
- Glands
- Hair
- Nails
342
What is the difference between thick and thin skin?
```
Thick skin
- Palm of hands and feet
- No hair
- 5 layers
Thin skin:
- rest of the body
- 4 layers
```
343
What cells are present in the stratum basale layer of the skin?
- Keratinocytes - produce keratin
- Melanocytes - responsible for skin colour
- Tactile cells - sense of touch
344
What cells are present in the stratum spinosum layer of the skin?
Thickest layer of epidermis
| - Keratinocytes - more flattered shape, more keratin
345
What cells are present in the stratum granulosum layer of the skin?
Keratinocytes - post mitotic, make large amounts of keratin and glycolipid
- Keratin forms durable filaments
- Glycolipid make skin water resistant
346
What cells are present in the stratum lucidum layer of the skin?
Exists ONLY in thick skin
| - Keratinocytes - densely packed - no nuclei or organelles
347
What cells are present in the stratum corneum layer of the skin?
Most superficial layer of the skin
- 15-30 layers of dead keratinised cells
- High lipid content
- Cells at surface flake off
348
What are the layers of the epidermis layer of the skin?
- Stratum basale (deepest layer)
- Stratum spinsosum
- Stratum granulosum
- Stratum lucidum (only in thick skin)
- Stratum corneum (top layer)
349
What is the life cycle of keratinocytes?
2-4 weeks
Migrate upwards and die on most superficial layer
Produce keratin
350
What are the layers of the dermis?
- Papillary layer - connective tissue
| - Reticular layer - irregular, dense connective tissue rich in collagen
351
What are the characteristics of the dermis layer of the skin?
- Thicker than the epidermis
- Irregular
- 2 layers
- Accessory structures (hair cells, swear glands)
- Blood vessels, sensory nerves, muscles
352
What is the hypodermic layer of the skin made up of?
- Connective tissue and adipocytes
| - Adipocytes provide a protective layer in babies
353
What are the two types of sweat glands?
```
Apocrine
- Secrete product into hair follicles of armpits
Merocrine
- 2-5 millions
- Secrete perspiration (500ml a day)
- Thermoregulation
```
354
Give the event that occur in thermoregulation?
```
Too hot
- Hypothalamus detects change and activates cooling
- Sweat glands activating
- Vasodilation
- Hair lies flat
Too cold
- Hypothalamus initiates heating
- Vasoconstriction
- Shivering
- Hair stands on end
```
355
How does the skin act as a barrier?
Physical barrier
- Toughness of keratin prevents entry of infectious agents
Biochemical barrier
- Sebum contains bactericidal substances
- sweat lowers pH to 4-6
Immunological barrier
- Langerhans cells in epidermis trigger immune response
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What vitamin does skin produce?
Vitamin D3
357
What is the function of the GI tract?
- Provides continual supply of water, electrolytes, vitamins and nutrients
- Moves food though the tract
- Circulates blood around the tracts to carry away the products of digestion
358
What is in the upper GI tract?
Buccal cavity
Oesophagus
Stomach
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What is part of the small intestine?
Duodenum
Jejunum
Ileum
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What is part of the lower GI tract?
Caecum
Rectum
Anal canal
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What are the functions of the buccal cavity?
Mastication
- teeth, tongue and saliva break down food
- Muscles involves are messeter, temporalis, pterygoids
- Saliva contains alpha - amylase which begins digestion
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What are the functions of the oesophagus?
- 20-25cm long
- Passes behind heart and trachea
- Consists of layers of muscles and connective tissue
- Performs peristaltic movements to push food down into the stomach
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What are the functions of the stomach?
- Hold up to 1lite of food
- Release proteases and HCL which smash up proteins and acts a bactericide
- Churns the contents producing chyme 40-60 mins
- Stomach releases chyme in small quantities to duodenum
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What is the function of the duodenum?
- C shaped struture next to the stomach
- Enzymatic breakdown of chyme occurs in the duodenum
- Four sections
- Duodenum regualates control of stomach emptying via secretin and cholecystokinin
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What is the function of jejunum?
- Absorption
- Finger like projection son inner surface to increase surface area
- Microvilli
- Active and passive transfer of nutrients
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What is the function of the Ileum?
- Subtle difference with jejunum
- Smaller lumen and thinner walls
- More fat
- Contains cells of the immune system
- Absorption of B12, bile salts and products
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What is the function of the large intestine?
- Absorb the remaining water and electrolytes from indigestible food matter
- Accept and stores food remains were not digested
- Eliminate solid waste from the body
- HCO3 buffers acid produced by bacterial fermentation
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What is the function of the caecum?
- Pouch - like structures that is considered to be the start of large intestine
- Chyme is pushed into it through the ileo-caecal valve
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What is the function of the rectum?
- Temporary store for faeces
- Final part of the large intestine
- Follows the shape of the sacrum
- The end expands into the rectal ampulla where the faeces is stored before defaecation
- Stretching of the rectal walls actives the desire to defaecate
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What is a possible cause for constipation?
Voluntary retention of faeces pushes it back into the colon where more water will be extracted
371
Why do we need to chew?
- Fruit and veg which have indigestible walls around the nutritious bits
- Enzymes work on surface of food particles so smaller particles - larger surface area: volume ratio
- Finer particles of food prevent excoriation of the GI tract and increases the ease the food is emptied from the stomach
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Outline the chewing reflex
- Presence of bolus in the mouth initiates reflex inhibition of the muscles of mastication
- Initiates the stretch reflex of the muscles of mastication leads to rebound contraction and elevation of mandible and closure of teeth
- Pushes food against the lining of the mouth which inhibits the muscles of mastication once again
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Outline peristalsis in the oesophagus
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Primary peristalsis
- Commences in oropharynx to stomach 8-10 seconds
- Gravity assist 5-8 seconds
Secondary peristalsis
- Sweeps down remaining food
- Trigger distension of oesophagus
Controlled by CNX and vagus nerve
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What is Barrett's Oesophagus?
- Abnormal change in the lining of the lower oesophagus
- Stomach acid reflux damage
- Stratified epithelial cells replaced will simple columnar epithelium
375
What are the symptoms of Barrett's Oesophagus?
- Heartburn
- Dysphagia
- Haemtemesis
- Erosion of teeth due to acid
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What are the treatments for Barrett's Oesophagus?
- Proton pump inhibitor
- Endoscopic surveillance
- Resection of the oesophagus
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How does the stomach fit more food in?
Food stretches the stomach and a vasovagal reflex from the stomach to the brainstem and back to the stomach reducing its muscular tone allowing it to stretch further and fit more in
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What is the role of the pylorus in the stomach and how is it controlled?
Slightly contracts to stop food passing through to the duodenum that is not fully mixed and fluid like
Controlled by nervous and hormonal signals
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What factors affect the rate of the stomach emptying?
Increasing the rate
- Increasing volume of food in there
- Gastrin - hormone
Decreasing the rate
- Stretch of duodenal wall
1. This directly inhibits pyloric pump via enteric nervous system in gut wall
2. Activates extrinsic nerves which inhibit sympathetic fibres
3. Vagus nerve to brainstem inhibits excitatory signal to the stomach
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What is a peptic ulcer?
Damage to the wall of the stomach by stomach acid due to heliobacter pylori or long term use of aspirin or ibuprofen
Causing a burning sensation in abdomen, indigestion and heart burn
381
What are the treatments for a peptic ulcer?
- Proton pump inhibitor - reduces stomach acid allow stomach to heal naturally
382
What are the symptoms and causes of gastric cancer?
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Symptoms
- Pain or burning sensation on swallowing
- Weight loss
- upper abdominal pain
- Feeling full after small amounts
- Bleeding
Causes
- Smoking
- Drinking
- Fatty food
- Not exercising
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383
What is the limiting factor for absorbance rate in the GI tract and how is it over come?
Surface area
- Folds of kerekring - developed in the duodenum and jejunum and increases surface area by 3 times
- Villi - projections from the surface area of the mucosa
- Microvilli - 1000s present on each epithelial cell
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How much is the small intestine capable of absorbing?
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Carbs - 100'sg
Fat- 100g
Amino acid - 50-110g
ions - 50-100g
Water - 7-8L
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How is water absorbed in the small intestine?
Transported through diffusion both through paracellular and transcelullar routes
Can move either way
386
How are Na+ ions absorbed in the small intestine?
Active transport across basolateral membrane
Less than 0.5% of intestinal Na is lost in faeces
Absorbs 25-35g/day
Co transporters used
- Sodium - amino acid
- Sodium - glucose
- Sodium - hydrogen exchangers
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How are fats absorbed in the small intestine?
- Fats are broken down into monoglycerides and free fatty acids
- These are emulsified by the liver secretion, bile into bile micelles
- Highly charged so highly soluble
- Micelles carried to the brush border of the epithelial cells and penetrate the recesses in between the agitating microvilli
- Monoglycerides and free fatty acids diffuse out of the micelle and into the epithelial cell
- taken up by SER
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What is the structure of the large intestine?
- Cecum
- Colon
- Tenia coli - 3 bands longitudinal muscle
- Haustra - pockets which give a segmented appearance
- No villi
- Lots of goblet cells - mucus
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What increases the absorption of Na+ in the large intestine?
Aldosterone
- Na+ and Cl- diffuse out
- More absorbed here than small intestine as tight junctions are smaller
390
What is the function of the colon?
Segmented contractions
- Retain material in procimalcolon for water reabsorption and fermentation
- Mixing contents
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What is the composition of faeces?
- 25% solid matter
- 3% protein
- 30% undigested
- 30% fat
- 30% dead bacteria
392
What causes the odour of faeces?
Caused by bacterial action and change depending on colonic flora and types of food eaten
393
What controls our hunger?
- Brain receptors
- Liver
- Stomach and intestines
- Fatty tissue
- External cues
394
What are the three main fates for nutrients?
- Supply energy
- Provide building blocks e.g. for proteins
- Stored for future
395
What are the main dietary constituents?
- Protein - growth and repair
- Fats - energy source
- Carbohydrates - energy source
- Mineral - inorganic elements needed for body processes
- Vitamins - important for chemical processes
- Water - 60% of human body
396
Why can't a single food supply all our anabolic needs?
- Because essential fatty acids cannot be synthesised and must be obtained by food
- Can only synthesis 11 out of 20 amino acids other 9 (essential amino acids) must be from diet
397
What proportion of food should be carbohydrates, fats and proteins?
57% carbs
30% fats
13% protein
398
What is the function of the liver?
Liver monitors blood glucose and as it begins to drop, it converts stored glycogen into usable glucose
399
What receptors activate hunger?
- Hypothalamic cells sensitive to dropping blood glucose
400
What tells us to stop eating?
- Stretch receptors in the wall of the stomach
- Chemoreceptors sensitive to small amounts of food dissolved in fluid
- The hormone cholecystokinin (CKK) released from duodenum
- Release of leptin from adipose tissue
401
What is the dual centre hypothesis?
Theory of how feeding behaviour is controlled - to simplistic
402
What are the suggested roles of Ghrelin and PYY3-36 hormones?
Ghrelin - secreted by stomach cells and increases food intake
PYY3-36 - secreted by intestinal cells and decreases food intake
403
How does PYY3-36 inhibitors appetite?
Selectively inhibits appetite - stimulating neurones by binding to receptor called NPY Y2.PYY3-36
The effects of PYY3-36 persist for 24 hours after which is why you're not hungry in the morning after a big dinner
404
What are the main causes of hypokalaemia?
- Diuretics - drug that elevates the rate of bodily urine excretion
- Hyperaldosteronism
- Bartter's syndrome and Gitelman's syndrome
405
What are the symptoms of hypokalaemia?
- Apathy
- Confusion
- Drowsiness
- Cardiac arrhythmias
- Weakness
406
What causes hyperkalaemia?
- Renal failure
- Drugs - ACE inhibitors and aldosterone
- Aldosterone deficiency
- Cell lysis
407
What is classified as hypothermia?
Core temperature below 35ºC
| Below 32ºC than fatal
408
What are the symptoms of severe hypothermia?
- Impaired judgement
- Pulse rate and blood pressure decrease
- Respiration becomes shallow
- Muscle stiffness
- Metabolic changes
- Ventricular arrhythmias - death
409
What does partial pressure mean?
Concentration of gases
410
What happens when [02] in arterial blood is low?
- Tachycardia
- Pulmonary vasoconstriction
- Pulmonary oedema - fluid build up around alveoli
- Cerebral oedema - fluid in brain
- Stimulates peripheral chemoreceptors
