Michaelmas Flashcards
(248 cards)
1
Q
What is systolic pressure, and why is the pulse pulsatile?
A
Peak pressure reached in vessels.
Represents the contraction of the heart, creating a pulsatile effect due to the elasticity of arteries.
2
Q
Explain diastolic pressure and its significance in circulation.
A
Minimum pressure reached in vessels.
Reflects the relaxation phase of the heart and is crucial for maintaining continuous blood flow.
3
Q
Describe arterial blood pressure, and why is it relatively uniform in all large arteries?
A
Pressure essentially the same in all large arteries.
Ensures consistent blood delivery to various tissues; large arteries have low resistance due to their large diameters.
4
Q
Explain Darcy’s Law, and how does it relate to blood flow?
A
Q = Pressure difference / Resistance.
Describes the relationship between pressure, resistance, and blood flow in circulation.
5
Q
What is Poisseuille’s Law, and how does changes in diameter affect resistance?
A
R = 8µL / πr^4.
Highlights the significant impact of diameter changes on resistance; arteries have lower resistance due to larger diameters.
6
Q
Explain the Fahreus-Lindwuist effect and when it’s observe
A
Describes how the viscosity changes with the diameter of the tube.
Occurs when the diameter of capillaries and red blood cells is too similar, leading to bolus flow.
7
Q
Describe fenestrated capillaries and provide an example of their location.
A
Capillaries with pores.
Found in the small intestine and glands; allows fast water flow, e.g., in the kidney.
8
Q
What characterizes sinusoidal capillaries, and where are they primarily located?
A
Capillaries with large gaps.
Found in the liver; allows the passage of proteins.
9
Q
What is capillary exchange, and how is it regulated?
A
of solutes across the capillary membrane.
Regulation: Governed by Fick’s Law; involves factors like surface area, permeability, capillary and interstitial fluid concentrations.
10
Q
Explain capillary exchange and the forces involved.
A
- Hydrostatic pressure (ΔP)
- Colloid osmotic pressure (Δπ); influenced by Starling Forces.
11
Q
What are Starling Forces, and what pressures do they involve?
A
The forces that drive the exchange of fluid through the walls of the capillaries
Involve hydrostatic and colloid osmotic pressures.
12
Q
Define autotransfusion and its significance.
A
Tissue fluid moves into capillary to buffer blood volume.
Prevents a significant drop in blood pressure when blood is lost.
13
Q
Explain oedema, its causes, and its effects.
A
Definition: Accumulation of excess fluid.
Causes: Filtration exceeding removal by lymphatics.
Effects: Increases distances between cells, affecting solute exchange; can occur in legs, lungs, etc.
14
Q
How are cardiac output and oxygen consumption related?
A
Cardiac output is usually proportional to VO2 (oxygen consumption).
Significance: Measurement of oxygen consumption is commonly used to indicate cardiac output.
15
Q
Describe the structure of arteriolar smooth muscle and its functions.
A
Circumferentially arranged.
Functions: Contraction results in vasoconstriction, and relaxation leads to vasodilation.
16
Q
What inhibits the binding of actin and myosin during arteriolar smooth muscle contraction?
A
Tropomyosin blocks the binding of actin and myosin.
Regulation: Removal of Tropomyosin by Ca2+ binding to Caldesmon, allowing actin and myosin to bind.
17
Q
What activates MLCK during arteriolar smooth muscle contraction, and what is the role of MLCK?
A
MLCK is activated by Calmodulin & Ca2+.
Outcome: Phosphorylation of MLC, promoting binding to actin.
18
Q
What are the factors for local and systemic control of arterioles?
A
Local Control: Metabolites(adenosine, CO2), O2 levels, Paracrine (NO).
Systemic Control: Hormones (adrenaline), Neurotransmitters.
19
Q
How does metabolism influence arteriolar resistance locally?
A
Lower PO2, increased PCO2, decreased pH lead to vasodilation.
Functional Hyperaemia due to local neuronal activity.
20
Q
Describe myogenic control of arteriolar resistance and its purpose.
A
Intrinsic ability of vessels to respond to changes in BP.
- Alters vascular tone
- Stretch activated Ca2+ channels are activated and cause depolarisations
Purpose
- Maintain perfusion to all organs
- Protect capillaries from high pressures
21
Q
What does LaPlace’s Law state, and how does it relate to arteriolar resistance?
A
Pressure = tension / radius.
Explains how changes in radius affect blood flow resistance.
22
Q
How does the endothelium contribute to arteriolar regulation through paracrine signalling, and what occurs if this is damaged?
A
Nitric Oxide (NO) signaling.
Mechanism: Acetylcholine stimulates NO synthase, leading to vasodilation.
Consequence: Loss in vasodilatory signaling, decreased blood supply.
Conditions: Hypertension, Smoking, Diabetes.
23
Q
How does noradrenaline and adrenaline affect arteriolar smooth muscle?
A
Noradrenaline:
α1 receptor.
Effect: Gq activation, leading to vasoconstriction via the Inositol pathway.
Adrenaline:
β2 receptors.
Effect: Gs activation, causing vasodilation via the cAMP pathway.
24
Q
What are eicosanoids, and what is their role in arteriolar regulation?
A
Arachidonic acid derivatives.
Synthesized by COX-1 which is inhibited my aspirin
1 = Prostaglandins (vasodilation)
2 = Thromboxanes (vasoconstrictive)
3 = Leukotrines (inflammatory response)
25
Why does the circulation require the heart to create a pressure gradient, and what is the stressed volume?
Reason: Circulation is a closed system. Necessary gradient between veins and arteries.
Stressed Volume: Extra blood (20%, 1L) to maintain positive pressure even when the heart isn't beating.
26
Why can't venous pressure (Pv) become negative, and what would happen if it did?
Pv cannot become negative to prevent vein collapse.
Negative Pv would create a gradient between Pv and Pa equaling mean systemic pressure (MSP), leading to negative Pv.
27
What role does vessel compliance play in maintaining a pressure gradient?
Veins are more compliant than arteries.
Formation of a pressure gradient due to differences in vessel compliance.
28
What factors determine cardiac output, and what is it dependent on?
Venous return (MSFP and resistance), rate of flow (RAP, SV).
29
How can MSFP be increased through extra filling, and what is the impact?
Blood transfusion increases volume.
Impact: Raises MSFP, leading to increased pressure.
30
How does venoconstriction impact MSFP?
Venoconstriction decreases capacitance, raising MSFP.
Outcome: Increased pressure due to reduced volume compliance.
31
What is Starling's Law of the Heart, and how does it relate to myocardial contractility?
Increasing preload (RAP) initially increases cardiac output.
Effect: Stretching of cardiac muscle enhances overlap between myosin and actin filaments.
32
How does Starling's Law of the Heart respond to increased afterload, and what changes occur in myocardial contractility?
Increased afterload leads to the heart pumping harder to maintain flow.
Contractility Changes: Stretching increases sensitivity to Ca2+, promoting more forceful contractions.
33
How does the autonomic nervous system influence cardiac output?
Sympathetic stimulation increases heart rate during exercise.
Autonomic control affects RAP, MSFP, and heart rate.
Adrenaline dilates at skeletal muscles beta 2 (Gs) , and vasoconstriction alpha 1 on vascular beds maintaining BP
34
What are the key factors and ways to increase cardiac output?
- Increase SV by enhancing venous return (preload) by raising MSFP through venoconstriction (veins have 70% of all blood).
- Increase HR
- Lower afterload/ resistance by vasodilation
- Increase blood volume
35
How does the heart maintain blood flow when afterload increases?
Increased afterload causes stronger forced contractions and stretching of cardiac muscle.
Outcome: Maintains blood flow even with increased resistance.
36
What is Guyton's curve, and what does it illustrate in the context of cardiac output and venous return?
Guyton's curve represents the relationship between cardiac output (CO) and venous return against venous pressure. Lower venous pressure is better and leads to higher cardiac output
37
What is the ABP equation, and what are its two main components?
ABP = CO × TPR.
CO = The volume of blood ejected by the heart per unit time
TPR = overall resistance to blood flow offered by the arterioles
38
What is Pulse Pressure?
It is the difference between systolic and diastolic blood pressure. Pulse pressure = Systolic BP - Diastolic BP. It reflects the force the heart generates with each contraction.
39
Where are high-pressure baroreceptors located, and how do they function in blood pressure regulation?
High-pressure baroreceptors are found in the Carotid Sinus and Aortic Arch.
Function: Activated by stretch, these baroreceptors send signals to the Nucleus Tractus Solitarius (NST) in the Medulla. This activation results in the inhibition of the vasomotor center and stimulation of the cardio-inhibitory center.
40
Where are low-pressure baroreceptors located, and how do they influence blood pressure?
Situated in the Atria and Pulmonary Vasculature.
Influence: Activated by changes in Right Atrial Pressure (RAP), these baroreceptors signal the NST in the medulla and the Hypothalamus. Their activation affects factors such as ADH secretion and renal physiology
41
What are the outcomes of denervation of high pressure and low pressure baroreceptors?
Denervation of high pressure baroreceptors leads to increased variability in blood pressure but same mean pressure is maintained
Denervation of low-pressure baroreceptors results in changes in mean pressure and increased variation in blood pressure.
42
What are the locations and activation mechanisms of arterial and central chemoreceptors?
Arterial chemoreceptors are located in the Carotid and Aortic Bodies.
Activation Mechanism: Arterial and central chemoreceptors are activated by a drop in PO2 (oxygen levels) and very low blood pressure
43
How does circulatory control adapt to exercise, and what changes occur in blood pressure?
1. Exercise leads to vasodilation in respiring muscles,
2. Causes a fall in Total Peripheral Resistance (TPR).
3. Arterial Blood Pressure (ABP) stays constant.
4. Blood Pressure: The demand for increased Cardiac Output (CO) during exercise is met by
5. Increasing Heart Rate (HR) and venoconstriction, compensating for the vasodilation.
(SHORT TERM)
44
What is Functional Hyperaemia, and in how many phases does it occur during exercise?
Increased blood flow to muscles during exercise, regulated by local mechanisms.
- Phase I, which is the rapid response to exercise (0-20s),
- Phase II, which involves the sustaining of higher blood flow (20s onward).
45
How does hyperpolarisation contribute to Phase I of Functional Hyperaemia?
Hyperpolarisation in Phase I is a result of increased interstitial K+, leading to closure of Ca2+ channels and muscle relaxation.
Hyperpolarisation Effect: Increased [K+] if activates Na/K ATPase and inward rectifying K+ channels (IRK+ channels), leading to hyperpolarisation, contributing to the relaxation of muscles.
46
What factors contribute to Phase II of Functional Hyperaemia? (5)
1. Extracellular K+: Continues to have a vasodilatory effect.
2. Circulation of Adrenaline: Acts on β2 receptors.
3. Release of NO from the Endothelium: Enhances vasodilation.
4. Low O2 Conditions: Lead to the production of vasodilatory adenosine from ATP.
5. Activation of PKA by Adenosine: Leads to the opening of K+ channels and movement of K+ out.
47
What is the concept of anticipatory increase in HR, and how is it demonstrated?
Anticipatory increase in HR (chronotrophy) involves an increase in heart rate in anticipation of exercise.
Demonstration: In a test where hand grip exercise is carried out, and HR increases, injecting Curare (paralysis) into the arm to prevent exercise still results in an increased HR, showcasing a feed-forward mechanism.
48
What evidence supports the notion that circulation is a limiting factor in exercise?
A test involving exercise with two legs showing less power output than double exercise with one leg indicates that circulation is a limiting factor. This suggests that reduced blood flow when both legs are working leads to higher resistance, impacting muscle performance.
49
What are the effects of hemorrhage on the circulatory system, and how is it detected?
Effects:
- Vasoconstriction to increase pressure.
- Changes in water control at the kidneys.
- Increase in HR, TPR, and decrease in capillary pressure for autotransfusion.
- Pain acts as a feed-forward mechanism.
Detection: Low-pressure baroreceptors and arterial baroreceptors detect reduced blood volume and pain, initiating the responses to counteract the effects of hemorrhage.
50
How does the circulatory system respond to hypoxia, and how is hypoxia detected?
Lack of O2 leads to systemic vasoconstriction, except to the brain, and lower HR.
Increased cardiac output and flow compensate for reduced O2 saturation.
Detection:
Primary Chemoreceptors: Detect hypoxia and initiate systemic vasoconstriction, except in the brain, and lower HR.
Secondary Chemoreceptors: Respond to the effects of hyperventilation, leading to an increase in cardiac output and HR, along with vasoconstriction to non-vital areas.
- Increase in lactic acid production causing metabolic acidosis
51
What is hypertension, and at what point is arterial blood pressure considered hypertensive?
Hypertension is a condition where arterial blood pressure exceeds 140/90 mmHg in humans
52
What are the two main types of hypertension, and what factors contribute to each?
Essential Hypertension (90%): Linked to aging, genetic factors, etc.
Secondary Hypertension (10%): Commonly associated with kidney disease or excess adrenaline/aldosterone.
53
Define atherosclerosis and elucidate its effects on blood vessels.
Atherosclerosis is the buildup of lipid deposits on vessel endothelium.
Effects:
- Narrowing of blood vessels.
- Downstream endothelial damage.
- Weakening of vessel walls leading to aneurysms.
- Cardiac ischemia causing angina pectoris.
54
Define cardiac concentric hypertrophy and outline its associated problems.
Cardiac concentric hypertrophy involves the heart growing inwards, resulting in less ventricular and atrial space.
Problems:
- Diastolic dysfunction.
- Increased risk of cardiac arrhythmias.
55
What are two primary approaches for treating hypertension, and what do they target?
Reduction of MSFP and Circulating Volume: Achieved through diuretics.
Hormone Antagonists: Targeting TPR by inducing vasodilation.
However lowering pressure (sensed as hypotension) is sympotamatic so not very pleasant, but important in the long run
56
Explain the positive feedback loop that occurs when cardiac muscles, mianly the ventricles fail to contract.
An increase in MSFP leads to increased RAP instead of CO.
Increase in RAP doesn't increase ABP.
Detected as low blood pressure, creating a positive feedback loop.
57
What causes oedema, and what is the mechanism behind its occurrence?
Increased pressure upstream of capillaries.
Mechanism: Leads to the movement of fluid out of capillaries into the interstitium.
58
Define cardiac arrhythmia and describe two types with their effects.
Cardiac arrhythmia is the failed coordination of myocytes.
Effects:
Atrial Fibrillation: Affects atrial contraction, leading to reduced cardiac output.
Ventricular Fibrillation: Terminal event in heart failure, incompatible with life.
59
Define shock and outline the types of shock.
Shock occurs when cardiac output is inadequate for sufficient metabolic substrates to tissues.
Causes:
- Blood loss (Hypovolemic Shock)
- Loss of vascular tone (Distributive shock)
- Septicaemia (infection/inflammation).
- Anaphylaxis (allergic reaction).
- Heart failure (Cardiogenic Shock)
60
Where is calcium predominantly stored, and what are the key roles of calcium?
99% of calcium is stored as Calcium Phosphate in bones, with the remainder in cells and only 0.1% extracellular.
Stabilizes membranes through surface charge screening.
Critical for preventing hypocalcemia-related tetany and managing hypercalcemia, which can lead to sluggish muscles and kidney stones.
61
What messengers regulate plasma calcium levels, and what are their primary targets?
Messengers:
- Parathyroid hormone (PTH).
- Calcitonin.
Targets:
Gut (absorption).
Kidney (reabsorption rate).
Bone (erosion vs. deposition).
62
What are PTH's primary effects on bone, kidney, and gut?
Bone: Increased dissolution.
Kidney: Increased reabsorption.
Gut: Increased absorption via VitD3.
- Also works with FGF23 to reduce phosphate uptake, Forster et al., 2006
63
How is Vitamin D3 synthesized, and what is the process of its activation?
Synthesis: Keratinocytes synthesize Vitamin D3 from cholesterol upon UVB exposure or acquired through diet.
Activation:
1. Stored in the liver.
2. Circulates as 25-OHD bound to a binding protein.
3. Converted to active form in response to PTH, decreased calcium levels
64
What are the effects of active 1,25(OH)2D in calcium homeostasis?
Upregulates calbindin protein, facilitating calcium transport across cells.
Minor role in promoting bone dissolution.
65
What is the role of calcitonin, and how is it stimulated? How does gastrin influence calcitonin secretion?
Inhibits osteoclasts, promoting bone deposition; synthesized in the thyroid gland in response to high Ca2+ levels.
Gastrin is believed to increase calcitonin secretion as an anticipatory response after a meal.
66
How is phosphate homeostasis closely linked to calcium, and what conditions affect phosphate levels?
Calcium and phosphate form hydroxyapatite crystals, a major component of bone
Parathyroid hormone (PTH) and calcitriol (active vitamin D) regulate both calcium and phosphate levels.
67
Define systemic circulation and pulmonary circulation.
Systemic Circulation: Circulation of blood in vessels to tissues and organs in the body.
Pulmonary Circulation: Circulation of blood to the lungs for oxygenation.
68
Explain the continuous flow and pulsatile pulse in circulation
Continuous Flow:Always continuous due to a forward pressure gradient
Pulsatile Pulse: Pulse is pulsatile due to the elasticity of arteries.
69
Define systolic and diastolic pressure.
Systolic Pressure: Peak pressure reached in vessels.
Diastolic Pressure: Minimum pressure reached in vessels.
70
Explain Poisseuille’s Law and its implications on blood vessels.
Changes in diameter have a great effect on resistance
Implications: Arteries (large diameters) have low resistance.
Arterioles (smaller diameter) have greater resistance, controlling blood flow.
71
Discuss the Fahreus-Lindwuist effect and when it is present
Present for the flow of blood in capillaries.
Bolus flow occurs due to the similarity in diameter between capillaries and red blood cells
72
Describe the types of capillaries (continuous, fenestrated, sinusoidal)
Continuous Capillaries: Most common, narrow tight junctions, allow water and ions.
Fenestrated Capillaries: Found in small intestine and glands, allows fast water flow.
Sinusoidal (Discontinuous) Capillaries: Large gaps, allows proteins across (e.g., liver)
73
Discuss capillary exchange through diffusion and the factors regulating it.
- A (Surface Area): Increase number of perfused capillaries, reduce diffusion distance.
- P (Permeability): Influenced by histamines, cytokines.
- Xc (Capillary Concentration): Rate of delivery and extraction from the capillary.
- Xif (Interstitial Fluid Concentration): Rate of use and extraction.
74
Discuss the factors influencing autotransfusion.
Autotransfusion: Tissue fluid moves into the capillary to buffer blood volume, helping maintain BP.
- Vasoconstriction
- Decrease in capillary pressure
- Hormonal fluid control (RAAS, ADH)
75
Explain the role and function of the lymphatic system and its return mechanism.
Collects fluid from capillaries to avoid swelling.
Returns via the thoracic duct.
Drains into the vascular system at the subclavian veins.
76
Define oedema and discuss its causes and effects
Occurs when the rate of filtration of fluid out of capillaries exceeds removal by lymphatics.
- Increases distances between cells affecting solute exchange.
Can occur in legs, lungs, and have detrimental effects.
77
What regulates the secretion of somatotropins (GHs)
Somatotropins (Growth hormones)
Regulation: Hypothalamus, Anterior pituitary
Negative Inhibition: Somatostatin.
Negative Ultra Short Loop: GHRH inhibits its own release. and GH inhibits GHRH
78
What are some key properties of GH?
Short half life of 20 minutes, also bound to protein
Pulse release
79
How does GH respond to fasting, and what are its roles in promoting gluconeogenesis and growth?
Role in fasting:
- Promotes gluconeogenesis.
- Causes adipose tissue to release FFA.
- Exhibits diabetogenic effects, preventing glucose uptake by muscles and adipocytes.
Role in growth:
- Increase aa uptake by muscles
- Enhance protein synthesis
- Promotes cellular differentiation
80
How does GH impact growth plates?
Chondrogenesis
1) Chondrocytes lay down cartilage.
2) Cartilage becomes calcified and ossifies.
3) Chondrocytes proliferate, undergo hypertrophy, and then die.
- Until fusion of plates occurs
81
What challenges were posed to the Somatomedin Hypothesis, and what is the Dual Effector Hypothesis?
1. GH injection into the growth plate stimulates growth.
2. IGF antiserum injected with GH shows no growth.
3. Removal of liver-derived IGF-1 (gene knockout) still results in growth.
4. IGF-1 is produced locally in response to low IGF levels, forming the Dual Effector Hypothesis.
Dual Effector Hypothesis:
- GH stimulates differentiation of chondrocytes in the growth plate.
- GH stimulates the formation of IGFs, driving further growth.
82
Why doesn't GH promote growth during starvation, and what hormonal interactions are involved?
IGF-1 = reduced
Cortisol = Increases and causes protein catabolism
Fibroblast growth factor (FGF21)= released from the liver during fasting promotes GH resistance and reduces IGF-1.
83
How does growth occur in utero, and what role do IGF-1 and IGF-2 play?
- No Pituitary Growth Hormone Required.
- IGF-1 and IGF-2 are present.
- People with pituitary dwarfism are born at a normal size, as GH not required.
- IGF2 is essential for growing the placenta and aiding nutrient transfer.
84
What are the key components of the adrenal gland and their associated hormones?
Zona Glomerulosa: Secretes aldosterone, a mineralocorticoid regulating mineral balance.
Zona Fasciculata: Produces cortisol, a glucocorticoid influencing blood glucose levels.
Zona Reticularis (including Fetal Zone): Secretes androgens, primarily dehydroepiandrosterone (DHEA), contributing to androgen levels.
Medulla: Produces adrenaline, a catecholamine involved in the fight-or-flight response.
85
What are corticosteroids, and how is adrenaline secreted in the adrenal medulla?
- Steroid hormones released from the adrenal cortex e.g. aldosterone (mineralocorticoid), cortisol (glucocorticoid)
- Travel bound to plasma proteins, and bind to intracellular receptors.
Commonly long-acting hormones.
Adrenaline (NOT a corticosteroid) Secretion:
-Secreted by Chromaffin cells in the adrenal medulla.
- Conversion from noradrenaline to adrenaline is facilitated by PNMT (methyl transferase), induced by cortisol.
86
How is the adrenal cortex controlled, and what is the role of the HPA axis?
HPA Axis (Hypothalamic-Pituitary-Adrenal Axis)
1. Hypothalamus releases corticotropin-releasing hormone (CRH).
2. Anterior pituitary releases adrenocorticotropic hormone (ACTH).
3. ACTH activates the adrenal gland.
87
What are the functions (5) of cortisol in fasting, and how is its release characterized?
1. Promotes breakdown of muscle for gluconeogenesis.
2. Exhibits a diabetogenic effect, reducing glucose uptake by muscles and adipocytes.
3. Stimulates liver enzymes for amino acid conversion to glucose.
4. Promotes FFA release from adipose tissue.
5.Preserve liver glycogen, avoid hypoglycaemia, which was the cause of deaths in chickens lacking pituitary gland
Travels bound to cortisol binding globulin (CBG) with a long half-life of 70 minutes.
Pulsatile release
88
How does cortisol respond to stress, and what role does it play in the immune system?
Acutely inhibits processes in the inflammatory response.
Induces immunosuppression, exacerbated by chronic stress.
89
Besides its primary functions, what are some additional actions of cortisol?
- Facilitates fetal maturation in preparation for birth.
- Enables smooth muscle response to adrenaline and angiotensin, allowing vasoconstriction.
- Influences mood, contributing to phenomena like jet lag.
- Exhibits some affinity to aldosterone receptors, displaying mild mineralocorticoid effects.
90
Where are the receptors that sense changes in partial pressures?
Peripheral, carotid artery, aortic arch, and blood-brain barrier receptors detect partial pressure changes.
Central chemoreceptors detect pH changes in the cerebrospinal fluid (CSF).
91
What are the key features and mechanisms related to the mechanical structure of the lungs?
1. Air-tight cavity with chest wall expansion tendency and lung collapse tendency.
2. Small air gap in the pleural cavity.
Pressure Profile:
Boyle's Law applied for flow. (PV=PV)
92
What are the key mechanical properties involved in respiration?
Elastic Lung and Chest Wall
Surface Tension
Compliance
93
How do pressure and volume relate in the respiratory system, and what characteristics define this relationship?
Sigmoidal relationship with hysteresis behavior.
Increasing volume leads to decreasing pressures
94
What are transmural pressures, and how do they impact lung expansion?
Pressure across a biological membrane. (inside- outside)
Positive transmural pressure expands alveoli.
95
What is compliance, and what factors affect it in the respiratory system?
Compliance: Slope of the pressure-volume graph.
Elastic properties, lung size, and surface forces.
96
How does regional compliance vary in the lungs, and what is its impact?
Gravity-induced compliance variation, with the apex being less compliant than the base.
Alters alveolar ventilation at different lung regions.
97
What are the determinants of the elastic characteristics of the chest wall and lung?
Chest wall rigidity, shape, and compliance.
Internal elastic properties of the lung, influenced by surface tension.
98
What is surface tension, and how does it impact lung compliance?
Property of the liquid surface resisting external forces due to cohesive properties of molecules.
- Surfactant on alveoli contributes to lung compliance
99
How is pressure in the alveoli bubble defined, and how does Laplace's Law apply?
Laplace's Law in Alveoli:
Pressure = 2 x tension/ radius
Pressure determined by surface tension and radius
- Modified numerator due to a single air-liquid interface.
100
What evidence supports the impact of surface tension on lung mechanics, and who conducted relevant experiments? (2)
1. Von Neergaard's experiment with cat lungs filled with saline and air.
Surface tension accounts for 2/3 of lung elastic recoil.
2. Langmuir trough, surfactant similar to detergent
101
What is surfactant, and what roles (3) does it play in the respiratory system?
Surfactant is DPPC, polar, reducing surface tension
Role:
1. Reduces surface tension, increases compliance
2. Allows coexistence of alveoli of different sizes
3. Prevents collapse
102
How is surfactant organised, and what factors influence its organisation?
Smaller surface area results in crowded DPPC, requiring new surfactant for a uniform film.
Factors:
Lung volume changes affect surface area and surfactant arrangement.
- Potential reason for hysteresis seen in pressure-volume graph
103
Why is surfactant crucial in the respiratory system, and how does it relate to Infant Respiratory Distress Syndrome (IRDS)?
Lacking alveolar type II cells if born premature
So struggle to breath
104
What factors influence airway resistance, and how does lung volume affect resistance?
Factors: Lung volume, smooth muscle contraction, gas viscosity and density.
Increased lung volume reduces bronchi resistance.
105
How does dynamic airway compression occur, and what is the Equal Pressure Point (EPP)?
Dynamic Compression: Flow rate becomes effort-independent; highest at high lung volumes.
EPP: Point where transairway pressure reaches 0, beyond which airway tends to collapse.
106
What does Henry's Law state, and how is it related to partial pressure?
Concentration = Partial pressures x Solubility
Describes the solubility of gases in liquids.
The partial pressure of a gas is directly proportional to its solubility in a liquid.
107
What are the solubility coefficients for CO2 and O2, and how do they impact their diffusion rates?
CO2 Solubility: 0.7 ml/litre plasma/mmHg.
O2 Solubility: 0.03 ml/litre plasma/mmHg.
-- CO2 is 23 times more soluble than O2
108
What factors contribute to equilibration across the alveoli, and how is diffusion maintained?
Continuous maintenance of a diffusion gradient.
Alveolar ventilation (half) and pulmonary blood flow (half).
Transit Time: CO2 and O2 transit times through the venous pulmonary capillary are crucial for equilibration.
109
How is oxygen transported in the blood, and what are the two forms it takes?
Dissolved: Limited to around 90 ml/min
Bound to Hb: Forms a reversible bond with Hb, with each gram of Hb combining with 1.39 ml of O2 per gram.
110
Describe the structure of hemoglobin and factors affecting its affinity for oxygen.
Quaternary structure with 4 polypeptide chains (2α and 2β) and heme moieties.
Affinity affected by: Temperature, pH, and 2,3-DPG (diphosphoglycerate).
111
Explain the sigmoidal nature of the oxygen-hemoglobin dissociation curve and its significance.
Curve shows a cooperative binding of oxygen (sequential).
Above 60 mmHg, Hb is largely saturated; below 60 mmHg, small pressure changes lead to significant drops in saturation.
112
What is the significance of shifting the oxygen-hemoglobin dissociation curve, and what factors cause a right shift?
Right shift (decreased affinity) means less Hb saturation at the same pressure.
e.g. Bohr effect (pH and CO2 changes).
113
What is the role of 2,3-DPG on adult hemoglobin, and how does it impact oxygen affinity?
Induces a right shift in the curve, decreasing hemoglobin's affinity for oxygen.
Produced by RBC in response to low pH, low O2, and increased temperatures
e.g. during exercise, increases O2 unloading
114
How does fetal hemoglobin differ from adult hemoglobin, and why is this difference significant?
2α and 2γ globin chains.
Greater affinity for oxygen, less affected by 2,3 DPG
115
How are exogenous and endogenous factors related to the effects on hemoglobin saturation and affinity?
Exogenous Factors: Temperature change, pH change, PO2 change.
Endogenous Factors: 2,3-DPG.
116
What does the oxygen content of blood include, and how is it calculated?
Oxygen content = (Hb concentration × Oxygen saturation × Oxygen solubility) + Dissolved O2.
117
What are the effects of carbon monoxide poisoning, and how is it treated?
Higher affinity than O2, leading to decreased O2 content.
Left shift in the curve.
No color change in Hb.
Pure O2 therapy with high partial pressures to compete against CO
118
Outline the three main forms in which CO2 is transported in the blood and their respective percentages.
Dissolve (5-10%)
Bicarbonate (90%)
- Catalysed by Carbonic anhydrase
Carbamino compounds (5%)
- part of amino group
119
What is the Haldane effect, and how does it modulate the CO2 content of blood?
Increase in PO2 decreases Hb’s affinity to CO2, leading to less CO2 content.
Deoxygenated blood can carry more CO2.
120
How does deoxygenated hemoglobin act as a weak acid and contribute to the CO2 transport process?
Deoxygenated Hb acts as a weak acid, binding to more H+ at physiological pH. This maintains an H+ gradient favoring the production of HCO3-.
Deoxygenated Hb forms more carbamino compounds
121
Outline the steps involved in the transfer of CO2 at the tissues and its impact on pH and oxygen unloading.
1. PCO2 Gradient: PCO2 higher at respiring tissues than in plasma.
2. CO2 Dissolves: CO2 dissolves in blood, forming carbamino compounds.
3. Diffusion to RBC: CO2 continues to diffuse into RBC.
4. Hydration in RBC: CO2 hydrates in RBC via carbonic anhydrase.
5. HCO3- Production: HCO3- production leads to H+ release, lowering pH.
6. pH Impact: Low pH leads to more O2 unloading due to the Bohr effect.
7. Carbamino Binding: Deoxygenated Hb binds better to CO2.
8. Haldane Effect: Lower PO2 leads to more [CO2] Haldane effect.
122
Explain the bicarbonate buffer system, its dissociation constant, and how it helps maintain pH stability.
Buffer System: Involves conversion of CO2 to HCO3-.
Low dissociation constant (6.1) stabilizes pH with small changes.
Henderson-Hasselbach Equation: pH = 6.1 + log ([HCO3-]/[CO2]).
- Acts as an open buffer system, effective against acidic conditions.
- Can control CO2 levels through hyperventilation and HCO3- retention at the kidneys.
123
Differentiate between bronchial and pulmonary circulations in terms of their functions.
Bronchial Circulation (Conducting Airways)
- Warms and humidifies air.
- Protects against pathological effects of cold air.
Pulmonary Circulation (Respiratory Zone):
- Site for gas exchange.
- Acts as a filter and serves as a blood reservoir.
124
List the key functions of pulmonary circulation.
Blood reservoir
- 10% of blood is present always
- oxygenates all of blood = SV
Site of metabolism for Angiotensin I
Filtration
- Of blood clots, due to redundancy of capillary beds
125
Compare the structural differences between pulmonary and systemic circulations.
Pulmonary Circulation:
- Passive.
- No autonomic control.
- Branched, tortuous.
- Lower pressures.
Systemic Circulation:
- Active.
- Under autonomic control.
- Parallel.
126
Explain the significance of pulmonary vascular resistance and how it is different from systemic resistance.
All cardiac output passes with a high flow but low pressure gradient.
Darcy’s law leads to low resistance (1/10 of systemic resistance)
Pressure measured using Swan-Ganz catheter.
127
Explain the two factors contributing to lower resistance in the pulmonary vasculature.
Many Capillaries: Provides redundancy and allows for the recruitment of vessels to mediate changes in flow.
Compliance: Vessels are compliant, easily dilated to accommodate changes in volume.
128
Describe the relationship between pulmonary vascular resistance and cardiac output
Increase in Flow = Increase in Pressure = Decrease in Resistance
**Scenario 1 - Increase in cardiac output
1. Leads to an increase in pulmonary arterial pressure
2. Large increases accommodated by Capillary recruitment and capillary distension
**Scenario 2 - Decrease in Cardiac Output:
Changes in flow lead to a small decrease in pressure due to higher resistance in pulmonary vasculature.
129
How does lung volume impact pulmonary vascular resistance?
Types of vessels:
1. Alveolar vessels in contact with alveoli are directly affected.
2. Extra-alveolar vessels not in contact with alveoli are influenced by intrapleural pressures, more negative leading to dilation.
130
Explain the relationship between the radius of vessels and flow according to Poiseuille’s Law.
Decreasing radius decreases flow, due to an increase in resistance
Q = (pi x pressure x r^4)/( 8 x viscosity x length)
Re-arrangement of equation generates R = 8 x viscosity x length / pi x radius ^4
131
How does alveolar hypoxia influence pulmonary vascular resistance?
Regional Hypoxia:
- Localized vasoconstriction and shunting. (incr PVR)
- Little change in arterial pressure.
General Hypoxia:
- General vasoconstriction.
- Increased resistance according to Poiseuille’s Law, leading to increased pressure.
- Can result in oedema and chronic hypoxia.
132
Explain the critical role of low pressure in maintaining fluid balance at pulmonary arterial capillaries.
Require a low pressure to prevent large volumes of water moving out of the capillary and impairing gas exchange
Water moving out is removed by the lymphatics
- Net hydrostatic pressure is 16 mmHg (10 from MBP and 6 from -ve interstitial pressure)
- Net colloid osmotic is 12 (28 in interstitial fluid and 16 in interstitial space)
Prevention of water into alveoli
- Surfactant acts as barrier
- Negative interstitial pressure pulls water out
133
List and briefly explain the causes of pulmonary oedema. (5)
1. Increase in Arterial Pressure:
- Due to left heart failure. Greater movement of water out of capillaries, not fully removed by lymphatics, leading to pulmonary edema.
2. Increase in Capillary Permeability:
- Due to oxygen therapy or ozone toxicity.
3. Decrease in Capillary Colloid Osmotic Pressure:
- Less plasma proteins, as seen in starvation. = Kwashiorkor disease
4. Increase in Surface Tension:
- Due to defects in surfactant production.
5. Lymphatic Blockage:
- Inflammation, pathogen.
134
Explain the differences between osmotic movements of water in fresh water drowning vs. salt water drowning.
Fresh Water Drowning:
- Higher water potential in alveoli leads to water movement into pulmonary capillaries and RBCs, causing them to burst.
- Bursting releases K+ leading to cardiac fibrillation and death. Salt Water Drowning:
- Greater osmolarity in plasma causes fluid movement out, leading to pulmonary edema and death by asphyxiation.
135
Describe the gravitational effect on blood flow to the lungs and the three zones in the lungs.
Blood flow is greater at the base than the apex.
Zone 1 (Apex): Alveolar pressure is greater than arterial pressure, causing capillary collapse (theoretically no flow).
Zone 2 (Middle): Arterial pressure is greater than alveolar pressure, venous pressure has no influence
Zone 3 (Base): Arterial and venous pressures are greater than alveolar pressure, normal flow occurs.
136
Explain the normal average ventilation-perfusion ratio and the effects of VA/Q mismatch on gas exchange.
Normal Average Ratio: 0.8
- Mismatches can profoundly affect gas exchange.
- Ratio moves from high to low as you move down the lung.
- Mismatch situations affect mixed venous gas concentrations
~~ TB tends to localize near the apex where the ratio is high.
137
Explain the compensation mechanisms for low and high VA/Q ratios.
Low VA/Q Ratios: Characterized by high PCO2 and low PO2.
- Response includes an increase in overall ventilation and regional constriction to induce local hypoxia, shunting blood away from poorly ventilated alveoli.
High VA/Q Ratios: Characterized by low PCO2 and high PO2.
- Response involves wasted ventilation, a decrease in CO2 leading to increased pH, which affects vasoconstriction.
138
How do venous admixtures affect systemic arterial PO2, and what are the causes of venous admixture?
Wasted air or blood without corresponding perfusion or ventilation.
Causes include shunting, alveolar shunting, and low VA/Q ratio.
Venous admixture decreases PO2 but has little effect above 60 mmHg.
139
Explain the relationship between elevation, barometric pressure, and changes in PO2.
As elevation increases, barometric pressure decreases, leading to decrease in PO2.
At High Altitude:
To maintain alveolar PO2, alveolar ventilation must be increased significantly. However can lead to respiratory alkalosis as lots of CO2 is removed
140
How is hyperventilation controlled, and what are the roles of central and peripheral chemoreceptors?
Central Chemoreceptors: Detect pH changes in cerebral spinal fluid.
= Hyperventilation leads to a decrease in PCO2, making the environment more alkaline and reducing the hyperventilation stimulus.
Peripheral Chemoreceptors:
= Chronic hypoxia increases the ventilation stimulus via peripheral chemoreceptors, becoming dominant and causing further increases in ventilation.
141
How do changes in pressure affect the rate of diffusion?
Decrease in pressure gradient leads to a decrease in the driving force for diffusion.
This means diffusion can be slower and take up part of the reserve time
142
How does polycythemia affect oxygen content in the blood, and provide an example?
Increase in RBC concentration increases O2 content in the blood.
- Peruvian Andes residents have a higher O2 concentration in 100ml of blood compared to normal.
143
What is the common effect of an increase in altitude, and what can it lead to?
1. Low oxygen leads to vasoconstriction, diverting blood
2. Leads to pulmonary hypertension
3. More fluid moves out of the capillary than can be removed
4. cause pulmonary oedema.
144
How does 2,3 DPG influence the oxygen-hemoglobin dissociation curve, and what are the effects?
Causes a right shift
- Increases the amount of O2 unloaded at tissues.
- Decreases O2 loading at the lungs.
- Chronic hypoxia leads to a permanent right shift due to increased 2,3 DPG production.
- Also a drop in pH due to metabolic acidosis from the production of lactic acid
145
What difficulties are associated with hyperbaric breathing, and how does a SCUBA tank work?
Greater depth means greater pressure, making it more difficult to expand lungs.
+ During ascent, air expands, so one should not hold their breath due to changes in nitrogen solubility and bubbles potentially forming.
SCUBA tank: Delivers air at the pressure of the environment, adjusting to the surrounding hydrostatic pressure at different depths.
146
Explain how increasing pressure affects nitrogen solubility
- Increasing pressure leads to more N2 dissolved in the blood.
- Slow equilibration between tissues and blood.
- Ascent leads to decompression, and N2 moves out of solution.
DANGERS:
- Fast ascension leads to fast decompression, which causes N2 bubbles to form = "the bends"
- N2 can also act as a narcotic
147
What are the treatments for complications in SCUBA diving?
1. Hyperbaric/decompression chamber—put back under pressure and decompress slowly.
2. He-O SCUBA tank removes nitrogen. And reduces resistance to airflow, due to different density
148
Under normal conditions, what is the rate-limiting factor in exercise
Rate-Limiting Factor: Diffusion and the respiratory system are not rate-limiting under normal conditions.
Cardiac output is, as evidenced by the experiment where doubling blood flow to only one leg led to greater work than work done by two legs
149
What factors affect the relationship between ventilation and workload? (4)
1. Metabolic rate- workload increases, so does metabolic rate and ventilation to support the increase
2. Oxygen Demand- how much oxygen is taken up by muscles, if they're respiring aerobically
3. Anaerobic threshold - reached when glycolytic motor units are recruited, ventilation is required to buffer accumulation of lactic acid
4. Training status- training can lead to a more efficient ventilation
150
What are the signs that the anaerobic threshold has been reached?
Reached when glycolytic motor units begin to be recruited.
Slow oxidative motor units are recruited first and respire aerobically.
Once all are recruited, fast glycolytic motor units are recruited.
Evidence: increase in lactic acid after the inflection point.
151
What are the neurogenic and humoral stimuli for increasing ventilation, and how do they differ in speed of response?
Neurogenic: Fast and rapid response initiated by peripheral and CNS.
~ Denervation of peripheral chemoreceptors results in the inability to control alveolar ventilation.
Humoral: Slower response, detecting and responding to CO2 and H+ concentrations in blood.
152
Why must osmotic pressure be controlled, and what are the main functions of the kidney in maintaining body fluid homeostasis?
Prevents cells from shrinking.
Main Kidney Functions:
1. Regulation of electrolyte concentrations.
2. Regulation of ECF pH.
3. Regulation of ECF volume.
4. Long-term regulation of blood pressure.
5. Regulation of extracellular osmotic pressure.
153
List the main functions of the kidney in maintaining systemic homeostasis.
1. Regulation of electrolyte concentrations.
2. Regulation of ECF pH.
3. Regulation of ECF volume.
4. Long-term regulation of blood pressure.
5. Regulation of extracellular osmotic pressure.
6. Excretion of metabolic wastes.
7. Regulation of erythropoiesis.
8. Activation of VitD3.
9. Gluconeogenesis.
154
What is the van’t Hoff equation, and what does it relate to in the context of body fluid homeostasis?
Volume = nRT/ π
n = amount of solute
R= gas constant
T= temp in K
π= osmotic pressure
Relates to the osmotic pressure and the movement of water across a semipermeable membrane.
155
Explain the techniques used for measuring fluid volumes in the body.
1. Simple Diffusion Technique: Known marker injected, equilibration, and collection for volume calculation.
2. Single Injection Method:
Single injection, concentration measured at intervals, extrapolated for time 0.
3. Constant Perfusion Method:
Infusion of marker at a constant rate, concentration stabilizes, then marker collection for volume calculation.
MARKER= thiosulphate
156
What are the essential criteria for a good marker used in fluid volume measurements?
1. Be restricted to one compartment.
2. Distributed evenly.
3. Not change the volume.
4. Not be excreted.
5. Non-toxic.
6. Easily measurable
e.g. Inulin
157
Outline the structure of the kidney, including its major components.
Kidney → Ureter → Bladder → Urethra.
Capsule → Cortex → Outer Medulla → Inner Medulla.
158
What does the renal tubule consist of, and what are the two types of nephrons?
Consists of nephron and collecting duct.
Two Nephron Types:
- Juxtamedullary nephron (15%): Renal corpuscles close to the medulla.
- Cortical nephron (85%): Renal corpuscles in the cortex.
159
Describe the renal blood supply, and what is the role of vasa recta?
- Mirrors tubular supply.
- Receives 25% of cardiac output.
- Vasa recta: Long, hairpin loops in the inner medulla, 1% of renal blood flow.
160
What are the components of the renal corpuscle?
1. Fenestrated capillary.
2. Podocyt (Prevent plasma proteins from entering ultrafiltrate)
3. Basement membrane.
161
What factors influence ultrafiltration?
Size and charge are critical.
Sieving: >70,000Da not filtered, <7000Da filtered.
Charge: Polycationic is more filterable.
162
How is the glomerular filtration rate (GFR) calculated, and what factors can affect it?
GFR = K[(Pc-Pb)-πc].
Factors Affecting GFR:
K (surface area)
Pc (renal arterial pressure)
Pb (intratubular pressure)
πc (plasma colloid pressure).
163
What pressures influence net filtration, and what is the significance of the glomerulus in this context?
Hydrostatic and colloid osmotic pressures (Starling forces).
Hydrostatic pressure greater leads to filtration.
Signifance: Equilibrium is not reached
164
What is micropuncture, and how was it used to study glomerular filtration?
Puncturing the glomerular capsule and measuring the fluid composition.
Glomerular filtrate was protein-free, suggesting selective filtration at the capsule
165
What are the mechanisms involved in responding to an increase in GFR, and how does each mechanism operate?
1. Myogenic Effect on Afferent Arterioles:
- Increased pressure activates stretch-activated non-selective cation channels, causing depolarization.
- Activates Voltage-gated Ca2+ channels (VGCC), leading to contraction.
2. Tubulo-glomerular Feedback:
- Increased flow rate delivers Na+ and Cl- to macula densa.
- NKCC2 transporter absorbs Cl-, leading to depolarization and VGCC opening.
- Macula densa releases ATP, causing afferent arteriole constriction.
3. Sympathetic Modulation:
- Increased sympathetic nerve activity raises catecholamines, causing α adrenergic constriction.
166
How does the comparison of GFR and urine formation rate indicate selective reabsorption, and what is unique about the composition of tubular fluid?
Suggests that 99% of filtrate is reabsorbed.
-Composition differences suggest selective reabsorption.
Tubular Fluid Composition: Isosmotic with plasma. [Na+] remains constant along the proximal tubule.
- Selective reabsorption of glucose, αα, HCO3-, and phosphate.
167
What does micropuncture suggest about reabsorption in the proximal tubule, and what are the key characteristics of this process?
70% of filtrate reabsorbed in the proximal tubule. = Conservatory and unchanged
However regulatory control occurs at the distal parts of the kidney tubule
168
What is clearance, and how does it allow the comparison of the kidney's handling of different substances?
Rate at which a substance is removed from the plasma by the kidneys.
Allows the comparison of how the kidney deals with various substances.
169
How is GFR measured using clearance, and what characteristics must an ideal substance for this measurement possess?
Use a freely filtered, non-secreted, non-reabsorbed, non-metabolized, and non-toxic substance (e.g., inulin).
1. Infuse inulin intravenously.
2.Monitor inulin concentration until constant.
3. Rate of infusion = Rate of excretion.
4. Measure inulin concentration in arterial plasma.
170
How is the ratio of Inulin clearance to the clearance of another substance used to determine if the substance is secreted or reabsorbed?
As Inulin is used to represent GFR,
Ratio >1 indicates secretion.
Ratio <1 indicates reabsorption
171
What are the primary passive and active tubular transport mechanisms, and what are the categories under which they operate?
Passive Mechanisms:
1. Diffusion (simple or between cells).
2. Facilitated diffusion (via proteins).
3. Solvent drag (movement with water).
Active Mechanisms:
1. Primary active transport (uses ATP directly).
2. Secondary active transport (coupled to ATP use).
3. Endocytosis (invagination of plasma membrane)
172
Describe the process of glucose reabsorption in the proximal tubule, and what is the significance of SGLT1 and SGLT2?
Na+-Coupled Secondary Active Transport (SGLT-1, 2)
Transport process:
- Transports 2Na+/Glucose (SGLT1) or 1Na+/Glucose (SGLT2).
- Facilitated diffusion of glucose out (GLUT1 + 2).
- Na/K ATPase moves Na+ back out of the cell.
Significance:
At normal glucose concentrations, all glucose is absorbed.
Above transport maximum (Tmax), excretion follows the rate of filter load (rare)
173
How are amino acids reabsorbed by the proximal tubule?
αα/Na+ coupled secondary active transporters (5 types).
174
Describe the process of protein reabsorption, including the breakdown of large proteins and smaller peptides.
Protein Reabsorption:
~ Large proteins (albumin) broken down by proteases. Then taken up by endocytosis.
~ Smaller peptides (Angiotensin II, ADH) broken down by peptidases
~ Reabsorbed via αα-coupled transport.
175
Explain the process of HCO3- reabsorption in the proximal tubule, including the involvement of transporters and enzymes.
1. Primary Active Transport of H+:
Decreases pH via NEH3 (Na/H antiporter .and H+ ATPase
2. Formation of Carbonic Acid (H2CO3): Carbonic anhydrase breaks down CA to water and CO2.
3. CO2 Diffusion into Cell
4. HCO3- Movement Out: Via Na/3xHCO3- (NBC1) secondary active transport and Cl/HCO3- antiporter.
176
How does plasma concentration affect rate of clearance?
At higher concentrations Tmax is reached because movement of many solutes are carrier mediated
The rate will end up matching inulin rate
177
What percentage of water and NaCl does the proximal tubule absorb, and what is the nature of fluid reabsorption?
Absorbs 65% water and NaCl.
Isosmotic fluid reabsorption.
178
What percentages of water and NaCl are absorbed in the Loop of Henle, and what mechanisms enable concentration in this segment?
10% water and 25% NaCl Uncoupling and counter-current multiplication.
Active transport out at the thick ascending limb.
179
How does the distal convoluted tubule differ in NaCl and water absorption, and what regulates Na+ reabsorption in this segment?
Absorbs more NaCl and little water.
Na+ reabsorption
- Regulated by aldosterone.
180
What regulates water permeability in the cortical collecting duct?
Water permeability regulated by ADH.
Entering fluid is hypoosmotic to blood plasma.
181
Describe the steps of urea movement in the inner medullary collecting duct, and what is the significance of urea in osmotic pressure?
1. ADH Increases Urea Permeability at Inner medullary collecting duct.
2. Urea Movement: Moves into interstitium down gradient.
3. Diffuses into thin parts of the loop of Henle.
4. Moves through tubules and out at the inner medullary collecting duct.
5. Urea Recycling: Contributes up to 50% of osmotic pressure.
182
What evidence supports isosmotic reabsorption, and how is it demonstrated in simple micropuncture experiments?
1. Sample at the glomerulus and the end of the proximal convoluted tubule.
No change in osmotic pressure.
2. Injection of inulin, which is not secreted or reabsorbed, results in increased concentration due to water reabsorption.
183
Describe the split oil-drop experiments and how they provide evidence for water reabsorption
1. Inject mineral oil into Bowman’s Capsule.
2. Second injection to split oil drops.
3. Oil drops move towards each other over time, indicating volume decrease, specifically water reabsorption.
184
What experiments provide evidence for active transport in the kidney, and how do they demonstrate the role of ATP?
1. DNP Treatment (Mitochondrial Uncoupler): No ATP results in 10% reabsorption compared to 27%.
2. Ouabain Treatment (Na/K Transporter Inhibitor): Ensures Na+ movement role, not Cl-.
Results in 10% reabsorption compared to 27%.
185
How does the vasa recta contribute to water and solute reabsorption, and what is unique about its capillary loops?
- Allows reabsorption without ruining the osmotic gradient.
- Long capillary loops that reabsorb and allow equilibration.
- Incomplete equilibration to carry away solute and water.
186
What is microcryoscopy, and how is it used to study the osmotic concentration in diluting and concentrating kidneys?
Uses microscopy at low temperatures. Measures melting points to estimate concentrations, in comparison to pure water 0°C.
Diluting Kidney: Inner medulla thaws first
Concentrating Kidney: Medulla thaws from the center outwards, then cortex.
Gradient throughout the entire medulla.
187
Describe the role of magnocellular neurons acting as osmoreceptors in the SON, and how they respond to changes in osmolality.
Magnocellular neurons in the SON. Act as osmoreceptors.
- Stretch-inactivated non-selective cation channels respond to osmolality changes.
- Decrease in osmolality leads to water movement in, increasing volume.
188
What is the role of ADH, and how does it regulate water reabsorption at the collecting duct?
ROLE: Increases water reabsorption.
Acts as a vasoconstrictor.
Collecting duct:
1. Binds to V2 receptors on the basolateral side.
2. G protein-coupled to adenylyl cyclase.
3. Forms cAMP, activating PKA.
4. PKA phosphorylates AQP2, increasing water permeability.
189
How is the volume of extracellular fluid determined, and what are the mechanisms controlling it?
Controlled by the Na+ content, because that then affects the movement of water
Experimental measurements:
1. Radioactive isotope injection and measuring dilution
2. Dye dilution technique
190
How does an increase in extracellular fluid (ECF) and arterial blood pressure (ABP) affect sodium excretion, and what are the steps involved in pressure natriuresis?
Increase in ECF leads to increased ABP, resulting in greater Na+ loss
- Increased ABP raises pressure in afferent arteriole and peritubular capillary.
Decreased reabsorption from interstitium to peritubular.
Decreased reabsorption from the tubule by interstitium.
- Secretion of ANP, which inhibits ADH
191
How does an increase in ECF influence colloid osmotic pressure, and what is the impact on sodium excretion?
Greater dilution leads to lower colloid osmotic pressure (COP)
- Increased GFR due to reduced colloid tendency to pull water back.
- Greater Na+ excretion.
- Lower COP in peritubular capillaries results in less movement of water.
- Reduced reabsorption from tubules.
192
How does sympathetic activation influence sodium excretion, and what are the direct effects on renal arterioles?
1. Increases renin secretion leading to Angiotensin II and Aldosterone.
2. Renal arterioles (efferent > afferent) constrict, reducing GFR.
3. Direct stimulation of Na+ reabsorption
193
Describe the steps in the Renin-Angiotensin-Aldosterone System, from renin secretion to the effects of Angiotensin II.
1. Renin secreted by smooth muscle cells in the afferent wall, catalyzes angiotensinogen to Angiotensin I.
2. Angiotensin-converting enzyme (ACE) converts Angiotensin I to Angiotensin II.
3. Angiotensin II stimulates Na+ reabsorption in the proximal convoluted tubule (PCT).
4. Stimulates aldosterone synthesis by acting on AT2 receptors in the adrenal gland.
5. Induces thirst and NaCl intake.
6. Causes vasoconstriction of the efferent arteriole, reducing GFR.
7. Decreases flow in peritubular capillaries, promoting more reabsorption.
194
What factors stimulate renin secretion from juxtaglomerular cells, and how does this contribute to the regulation of Na+ excretion?
Afferent arteriole acting as a baroreceptor detects a fall in pressure.
Renal sympathetic nerves via β1 adrenergic receptors.
Changes in composition/flow to macula densa signaling decreased GFR and NaCl reabsorption.
195
What are the effects of Angiotensin II on Na+ reabsorption, aldosterone synthesis, thirst, and arterioles?
1. Stimulates Na+ Reabsorption in PCT: Upregulates NHE3 (H+/Na+ antiporter).
2. Stimulates Aldosterone Synthesis:
3. Acts on AT2 receptors in the adrenal gland.
4. Stimulates Thirst and NaCl Intake.
5. Vasoconstriction of Efferent Arteriole:
-Direct effect on AT1 receptor.
- Vasoconstriction decreases GFR.
- Decreases flow in peritubular capillaries, promoting more reabsorption.
196
What are the actions of aldosterone, and what factors stimulate its secretion?
1. Promotes Na+ reabsorption (ENaC, Na/K ATPase).
2. Promotes K+ secretion and excretion. (substitute for Na+)
3. Promotes H+ secretion.
Stimulation:
- Increased plasma Angiotensin II.
- Increased plasma [K+].
- Decreased plasma [Na+].
Regulated by ACTH
197
What are the effects of Atrial Natriuretic Peptide (ANP) on sodium excretion, and how does it achieve these effects?
Increases Na+ excretion
1. Effect on Collecting Duct:
- Binds to Gs proteins.
- Increases guanylate cyclase.
- Increases cGMP, activating PKG.
- Phosphorylates ENaC and Na/K, inhibiting uptake.
2. Effect on Proximal Convoluted Tubule:
- Promotes secretion of dopamine from PCT cells.
- Dopamine acts on D1 receptors on PCT.
- Decreases NHE3 activity, reducing reabsorption.
3. Effect on Other Hormones:
- Inhibits renin secretion and ADH.
- Resulting in decreased Angiotensin and Aldosterone.
4. Effect on Arterioles:
- Dilates afferent arteriole, increasing renal blood flow (RBF).
- Increased pressure, reduced GFR.
- Decreased reabsorption into peritubular capillaries.
198
How is calcium regulated in the renal system, and what are the mechanisms involved in both uncontrolled and regulated reabsorption?
Uncontrolled Reabsorption:
- Paracellular reabsorption driven by positive transepithelial potential.
- 70% reabsorbed at the proximal convoluted tubule (PCT).
- 20% reabsorbed at the loop of Henle.
Regulated Reabsorption:
- Occurs at the distal and collecting ducts.
Parathyroid Hormone (PTH)
- Increases Ca2+ via gut by promoting vitamin D to calcitriol.
- Only free Ca2+ is filtered at the glomerulus.
199
Describe the mechanisms of calcium absorption at the lumenal and peritubular membranes of the proximal convoluted tubule (PCT) and thick ascending limb.
Lumenal Membrane: TRPV5/
TRPV6.
Peritubular Membrane: Ca2+ ATPase and Na/Ca exchanger (NCX) with low affinity.
Calbindin-D facilitates movement across cells.
200
How is phosphate reabsorbed, and what are the types of transporters involved at the lumenal and peritubular membranes of the proximal convoluted tubule (PCT)?
Lumenal Membrane:
- Type IIa (3Na/ HPO4^2-) = electrogenic transporter.
- Type IIc (2Na/ HPO4^2-) = electroneutral.
- Type III (2Na/ H2PO4-) = found later in the PCT when fluid becomes more acidic.
Peritubular Membrane (PCT):
- Na/K ATPase.
- Organic ion/phosphate antiporter.
201
How does parathyroid hormone (PTH) influence phosphate reabsorption at both the lumenal and peritubular sides?
Lumenal Side:
1. Activates PLC, creating IP3.
2. Increases intracellular Ca2+ levels.
3. Activates Phosphokinase C.
4. Phosphorylates Type II transporters, inhibiting them.
Peritubular Side:
1. Activates Gs, increasing cAMP.
2. Activates PKA, phosphorylating Type II transporters, inhibiting them.
- Phosphorylation of scaffold protein causes endocytosis of the transporter.
202
What is the role of calcitriol in increasing reabsorption of calcium and phosphate, and which transporters are affected?
- Increased reabsorption
- Increases expression of TRPV5 and TRPV6, Calbindin-D, and NCX.
- Also increases expression of Type II Na+/Pi transporter in PCT.
203
204
How is potassium homeostasis tightly regulated, and what are the hormonal and physiological mechanisms involved?
Kept at around 4.5mM
- Controlled by Aldosterone and Flow Rate
- Decrease in EC of K+ = Insulin, due to coupled uptake with glucose
- Acidosis causes H+ excretion in exchange for K+, however K+ is still secreted
- Plasma [K+] rises during exercise due to electrical activity and adrenaline.
205
What are the primary mechanisms involved in the regulation of potassium excretion, including the role of aldosterone and tubular fluid flow rate?
Aldosterone:
- Acts genomically due to being a steroid hormone.
- Increases Na/K ATPases, K+ gradient, and permeability to Na and K.
Tubular Fluid Flow Rate:
- Increased flow rate increases K+ secretion
206
Explain the buffering systems and the Henderson-Hasselbalch equation for pH regulation in the body.
Bicarbonate/Carbonic Acid.
Plasma proteins (residues).
Phosphate, can combine with H+
Ammonia converted to ammonium (trapping)
pH = pKa+ log (base/acid)
207
Describe the bicarbonate/carbonic acid buffer system, its pKa, and how it responds to changes in pCO2.
pKa: 6.1, indicating a poor buffer
pCO2 Above Normal Levels:
- CO2 diffuses into the blood-brain barrier, reacts with water, increasing CSF acidity.
- Detected by chemoreceptors, leading to increased ventilation
- Forms more HCO3-, and excess is eliminated by the kidneys.
208
Explain how bone acts as a buffer in both acute and chronic situations
Acute: Carbonates on the bone surface act as proton acceptors.
Chronic: In metabolic acidosis, cation exchange occurs.
209
How is non-volatile acid buffered in the extracellular fluid (ECF), and what are the primary steps involved?
1. Formation of sulfuric acid by cysteine catalysis.
2. Dissociation leads to decreased pH, buffered by carbonates, phosphates, and plasma proteins.
3. CO2 is lost via the lungs, and ammonia is lost in the urine.
210
How does the liver contribute to pH regulation?
-Catalyzes the breakdown of amino acids into NH4+ and HCO3-.
- Forms glutamine from ammonium and α-ketoglutarate.
- Forms urea from ammonium and HCO3-
211
Describe the transport of hydrogen carbonate in the proximal convoluted tubule, including the involved transporters and steps.
1. H+ ATPase and Na+/H+ antiporter decrease pH.
2. H+ reacts with HCO3- to form carbonic acid.
3. Catalyzed into CO2 and H2O by carbonic anhydrase.
4. CO2 diffuses into the cell, reacts with water.
5. Transported out of the cell as bicarbonate on transporters (NBC1 and AE1).
6. H+ is recycled back into the tubule.
212
Explain the transport of ammonium in the proximal convoluted tubule, including the steps involved and the transporters used.
Secreted out into the lumen
1. Glutamine moves in via transporters.
2. Broken down into NH4+ and bicarbonate.
3. Bicarbonate leaves cells via transporters (NBC1 and AE1).
4. NH4+ moves out into the tubular lumen using NHE3 (substituting for H+).
5. H+ is also moved out, causing paracellular movement of H+ via tight junctions.
213
Describe the reabsorption of ammonium in the loop of Henle
1. Moves in via NKCC2 channels (substituting for K+).
2. Moves out into the medullary interstitium via a symporter with Cl-.
3. Can move out via Na/K ATPase, substituting for K+.
4. Creates an electrochemical gradient, causing the diffusion of ammonia (NH3) across and NH4+ via tight junctions.
214
Explain the reabsorption of bicarbonate in the distal convoluted tubule (DCT) and collecting duct
1. Reabsorption occurs at Type-A intercalated cells.
2. Secrete H+ via H+ ATPase or H/K ATPase.
3. Decreases pH and forms carbonic acid, which dissociates.
4. CO2 diffuses into the cells, reacts with water.
5. Transporter out of the cell via AE1 (Cl-/HCO3-, antiporter).
6. Transport of HCO3- in DCT and Collecting Duct
215
Detail the secretion of ammonium in the collecting duct, outlining the steps and the role of rhesus glycoproteins.
- Secreted as NH3.
1. Ammonia (NH3) freely diffuses across the cell.
2. Reacts with H+, pumped out by H/K ATPases in the tubular lumen.
3. Forms ammonium (Ammonia trapping).
4. Protons secreted are produced from the dissociation of NH4+ to NH3+ and are buffered by bicarbonates.
Rhesus glycoproteins facilitate the secretion of ammonium into the urine in the collecting duct.
216
Describe the mechanisms of increased H+ secretion and HCO3- reabsorption in the renal system.
Mechanism of Increased H+ Secretion:
- Increased NHE3 Activity.
- Increased Na/H Exchange.
- More H/K ATPases.
Mechanism of HCO3- reabsorption:
- Distal tubule, HCO3- reabsorption is regulated by luminal Na+/HCO3- cotransporters (NBC1)
- Intercalated cells in the collecting duct can contribute to HCO3- reabsorption, primarily through luminal H+/K+-ATPase activity.
217
Differentiate between volatile acids and non-volatile acids, and explain their relevance to the bicarbonate/carbonic acid buffering system.
Volatile Acids: Can vaporize into gas form and be lost at the lungs as CO2.
Bicarbonate/Carbonic Acid Buffering: Plays a crucial role in handling volatile acids, allowing them to be excreted as CO2.
218
Detail the process of bicarbonate secretion in Type B intercalated cells in the collecting duct, and how it contributes to alkalosis.
1. Acidification of medullary interstitium.
2. Formation of carbonic acid, dissociates into carbon dioxide.
3. Carbon dioxide diffuses into cells.
4. Reacts with water, forms bicarbonate, and is transported out into the lumen (via AE1).
5. Opposite of Type A intercalated cells.
219
Define acidosis and alkalosis and explain how to calculate pH from pCO2 and [HCO3-].
Acidosis: Arterial plasma becomes more acidic.
Alkalosis: Arterial plasma becomes more alkali.
pH = 6.1 + log (HCO3-/ 0.03pCO2)
220
List and explain the categories of primary disturbance in acid-base balance
1. Metabolic Acidosis:
- Low HCO3-.
- Compensation: Increase breathing rate to remove acid, lowering pCO2.
2. Metabolic Alkalosis:
- High HCO3-.
- Compensation: Decrease breathing rate, resulting in higher pCO2.
3. Respiratory Acidosis:
- High pCO2.
- Compensation: Increase buffering of pCO2 by secretion and higher HCO3-.
4. Respiratory Alkalosis:
- Low pCO2.
- Compensation: Decrease pH by removing buffer, lowering HCO3-
221
Explain the primary and compensated respiratory alkalosis in response to challenges like high altitude.
Primary Respiratory Alkalosis:
- Low pO2 due to pressures, leading to increased ventilation rate and low pCO2.
Compensated Respiratory Alkalosis:
- Kidneys excrete HCO3- to restore HCO3: CO2 ratio.
222
Describe the pH challenges associated with diabetic ketoacidosis
- Lack of insulin leads to less glucose uptake and increase fat metabolism
- Incomplete oxidation of fatty acids, producing ketone bodies.
- H+ produced is buffered by HCO3-, leading to CO2 production.
- Increased ventilation rate leads to compensatory metabolic acidosis, lowering pCO2.
223
Discuss the pH challenges associated with primary aldosteronism (Conn's syndrome) and the role of aldosterone in acid-base balance.
- High levels of aldosterone lead to K+ secretion and metabolic alkalosis.
- Aldosterone non-genomically increases the action of K/H ATPase, promoting H+ secretion and HCO3- reabsorption, further causing metabolic alkalosis.
224
Outline the pH challenges associated with vomiting, including the secretion of gastric acid and the compensatory response.
- Gastric acid secretion leads to primary metabolic alkalosis.
- Ventilation rate slows down as part of the compensated metabolic alkalosis.
225
What is detraining?
Induced adaptations due to insufficient training.
- Overload (progressive increase), - Specificity (training of specific muscles for specific use),
- Reversibility (anything gained can be lost)
226
What are trained characteristics in endurance running?
- Greater mitochondria density
- Greater activation of protein kinase by AMP
- Activation of the master regulator PCG-1α.
- Increased phosphocreatine acting as an ATP buffer
- Increased blood volume (due to albumin), and increased SV, CO and so lowering resting HR
- Eccentric hypertrophy
227
What are the effects of short and long term detraining?
Short term:
- Blood volume decreases
- Decrease in SV and CO
- Increase in FFA (especially LDL)
Long term:
- Changes to muscle mass
- Mitochondria density changes
228
What are the effects of extreme bed rest?
3 weeks of bed rest is equivalent to 40 years of aging, on VO2 and CO
Test occurred in Dallas, and 5 people were tested and then came back 20 and 30 years later for testing
229
What are the roles of calcium in the body?
1. Surface charge screening- stabilises membrane, reducing ability for ion channels to open
2. Bone and teeth, as calcium phosphate
3. Cell signalling - muscle contractions (SER) and neurotransmitter release
4. Blood clotting - activation of thromboplastin
5. Cell division - regulation during mitosis
230
What are the different types of dwarfism and gigantism and the causes?
Pituitary dwarfism - failure to produce GH, small but proportional
Dwarfism of Sindh- defective GHRH receptor
Laron syndrome - defecting GH receptors
Achondroplasia - defective FGF receptor, can't produce cartilage so disproportionate
Gigantism - oversecretion of GH as a child
Acromegaly- oversecretion of GH as an adult
231
What is the difference between NCX and Ca ATPase?
NCX = Na/Ca exchange
- lower affinity, higher capacity
Ca ATPases
- higher affinity, lower capacity
232
What is Starling's law of the kidney and the equation for Net filtration rate?
Law describes factors that govern formation of urine
- Glomerular filtration rate (GFR)
- Hydrostatic pressure
- Oncotic pressure (colloid)
NFR = K x [(Pc-Pb) - (πc-πb)]
K= filtration coefficient
233
How did Starling demonstrate his law of the heart?
In the early 20th century carried out experiments on dog hearts
- Manipulated preload and saw changes in myofilament length
- Generated a graph of preload (representing stretch) against stroke volume (representing contractile force)
234
Detail the effects of growth hormone on a) muscle metabolism and growth and b) bone metabolism and growth.
Muscles:
i. Promotes amino acid uptake
ii. Increases protein synthesis rate
iii. Releases insulin like growth factor (IGF-1)
iv. Inhibits glucose uptake into muscles (diabetogenic effect)
Bone growth:
i. Amino acid uptake into chondrocytes (extra mark)
ii. Opposes closing of growth plate
235
What is the evidence for isosmotic fluid reabsorption occurring in the PCT? (2 Experiments)
1. Micropuncture
- Sample PCT tubule at both ends
- Measured using inulin
- Conc increases in proportion to volume loss
2. Split oil drop
- Drops move closer together, but osmolality is the same
236
What are the short and long term control mechanisms for blood pressure?
Short
- Vasoconstriction/ Vasodilation
- Functional hyperaemia
- Heart rate changes
- Starling's law of the heart
Long
- RAAS
- ADH
- ANP from atria
237
How does the ANS increase HR? (2)
- Lack of vagal parasympathetic ACh on muscarinic M2
- Sympathetic noradrenaline on β1 in SAN
238
How are proteins reabsorbed in the PCT?
- Amino acids via Na+ coupled transporters
- Large proteins via endocytosis
- Smaller proteins broken down to αα
or cotransported in
239
What evidence suggests that phase I functional hyperaemia (directly following contraction is [K+] dependent?
Oubain - Blocks Na/K ATPase
Barium - Blocks K+ channels, leads to reduced vasodilation
Timing of response - too fast for it to be other factors such as adenosine
240
What is the evidence for the GH/IGF duplex growth control system?
- Somatomedin hypothesis
- Lack of IGF or GH, leads to stunted growth
- Rapid growth rate correlated with increased levels of IGF-1
- GH administration leads to increased IGF-1 from the liver
241
What are the effects of changes to ABP on capillary pressure?
Increase in ABP - no change, vessels accommodate to prevent damage to capillaries
Decrease in ABP - decrease in capillary pressure, and regional vasoconstriction
242
What are the effects of heart failure on the circulatory system?
LHS - increase in venous pulmonary pressure, can lead to pulmonary oedema
RHS - increases systemic venous pressure, and increases capillary pressure, changing capillary exchange
243
How can Starling's forces governing capillary exchange be altered? (7)
Pc increase
- venous blockage
- RS heart failure
Pif decrease
- dehydration
πc decrease
- starvation
- liver failure
πif increase
- inflammation
- lymphatic blockage
244
What are the effects of training on cardiac output? (5)
1. Lower resting HR, more efficient
2. Increased capillary density
3. Eccentric hypertrophy, increase in contractility
4. Increase in blood volume
5. Enhanced endothelial function
245
Describe the control of bronchial smooth muscle
Constriction
- Parasympathetic cholinergic fibres
Dilation
- Sympathetic, adrenergic fibres
246
Why is it important to maintain levels of K+, how is it achieved?
- Important for repolarisation
- Important in Na/K ATPase, for Na+ retention
Increase in SK = greater loss
Insulin = Increase in Na/K = greater retention
H/K ATPase alterations - promotes uptake
247
What are the causes for metabolic acidosis?
Production of acids, with conjugate base
- NSAIDs
- Methanol/ Ethanol
- Lactic acid
- Diabetic ketoacidosis lack of insulin, FA, increase ketones
- Hypoaldosteronism, K+ retention increase in H+ secretion
- Inhibition of AE1, Type A, reduce HCO3- uptake
248
What are the causes for metabolic alkalosis?
- Greater K+ loss, H+ in cell not ECF (primary aldosteronism, blocks, Conn's)
