Michaelmas Flashcards
What is systolic pressure, and why is the pulse pulsatile?
Peak pressure reached in vessels.
Represents the contraction of the heart, creating a pulsatile effect due to the elasticity of arteries.
Explain diastolic pressure and its significance in circulation.
Minimum pressure reached in vessels.
Reflects the relaxation phase of the heart and is crucial for maintaining continuous blood flow.
Describe arterial blood pressure, and why is it relatively uniform in all large arteries?
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.
Explain Darcy’s Law, and how does it relate to blood flow?
Q = Pressure difference / Resistance.
Describes the relationship between pressure, resistance, and blood flow in circulation.
What is Poisseuille’s Law, and how does changes in diameter affect resistance?
R = 8µL / πr^4.
Highlights the significant impact of diameter changes on resistance; arteries have lower resistance due to larger diameters.
Explain the Fahreus-Lindwuist effect and when it’s observe
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.
Describe fenestrated capillaries and provide an example of their location.
Capillaries with pores.
Found in the small intestine and glands; allows fast water flow, e.g., in the kidney.
What characterizes sinusoidal capillaries, and where are they primarily located?
Capillaries with large gaps.
Found in the liver; allows the passage of proteins.
What is capillary exchange, and how is it regulated?
of solutes across the capillary membrane.
Regulation: Governed by Fick’s Law; involves factors like surface area, permeability, capillary and interstitial fluid concentrations.
Explain capillary exchange and the forces involved.
- Hydrostatic pressure (ΔP)
- Colloid osmotic pressure (Δπ); influenced by Starling Forces.
What are Starling Forces, and what pressures do they involve?
The forces that drive the exchange of fluid through the walls of the capillaries
Involve hydrostatic and colloid osmotic pressures.
Define autotransfusion and its significance.
Tissue fluid moves into capillary to buffer blood volume.
Prevents a significant drop in blood pressure when blood is lost.
Explain oedema, its causes, and its effects.
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.
How are cardiac output and oxygen consumption related?
Cardiac output is usually proportional to VO2 (oxygen consumption).
Significance: Measurement of oxygen consumption is commonly used to indicate cardiac output.
Describe the structure of arteriolar smooth muscle and its functions.
Circumferentially arranged.
Functions: Contraction results in vasoconstriction, and relaxation leads to vasodilation.
What inhibits the binding of actin and myosin during arteriolar smooth muscle contraction?
Tropomyosin blocks the binding of actin and myosin.
Regulation: Removal of Tropomyosin by Ca2+ binding to Caldesmon, allowing actin and myosin to bind.
What activates MLCK during arteriolar smooth muscle contraction, and what is the role of MLCK?
MLCK is activated by Calmodulin & Ca2+.
Outcome: Phosphorylation of MLC, promoting binding to actin.
What are the factors for local and systemic control of arterioles?
Local Control: Metabolites(adenosine, CO2), O2 levels, Paracrine (NO).
Systemic Control: Hormones (adrenaline), Neurotransmitters.
How does metabolism influence arteriolar resistance locally?
Lower PO2, increased PCO2, decreased pH lead to vasodilation.
Functional Hyperaemia due to local neuronal activity.
Describe myogenic control of arteriolar resistance and its purpose.
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
What does LaPlace’s Law state, and how does it relate to arteriolar resistance?
Pressure = tension / radius.
Explains how changes in radius affect blood flow resistance.
How does the endothelium contribute to arteriolar regulation through paracrine signalling, and what occurs if this is damaged?
Nitric Oxide (NO) signaling.
Mechanism: Acetylcholine stimulates NO synthase, leading to vasodilation.
Consequence: Loss in vasodilatory signaling, decreased blood supply.
Conditions: Hypertension, Smoking, Diabetes.
How does noradrenaline and adrenaline affect arteriolar smooth muscle?
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.
What are eicosanoids, and what is their role in arteriolar regulation?
Arachidonic acid derivatives.
Synthesized by COX-1 which is inhibited my aspirin
1 = Prostaglandins (vasodilation)
2 = Thromboxanes (vasoconstrictive)
3 = Leukotrines (inflammatory response)
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.
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.
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.
What factors determine cardiac output, and what is it dependent on?
Venous return (MSFP and resistance), rate of flow (RAP, SV).
How can MSFP be increased through extra filling, and what is the impact?
Blood transfusion increases volume.
Impact: Raises MSFP, leading to increased pressure.
How does venoconstriction impact MSFP?
Venoconstriction decreases capacitance, raising MSFP.
Outcome: Increased pressure due to reduced volume compliance.
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.
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.
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
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
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.
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
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
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.
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.
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
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.
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
How does circulatory control adapt to exercise, and what changes occur in blood pressure?
- Exercise leads to vasodilation in respiring muscles,
- Causes a fall in Total Peripheral Resistance (TPR).
- Arterial Blood Pressure (ABP) stays constant.
- Blood Pressure: The demand for increased Cardiac Output (CO) during exercise is met by
- Increasing Heart Rate (HR) and venoconstriction, compensating for the vasodilation.
(SHORT TERM)
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).
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.
What factors contribute to Phase II of Functional Hyperaemia? (5)
- Extracellular K+: Continues to have a vasodilatory effect.
- Circulation of Adrenaline: Acts on β2 receptors.
- Release of NO from the Endothelium: Enhances vasodilation.
- Low O2 Conditions: Lead to the production of vasodilatory adenosine from ATP.
- Activation of PKA by Adenosine: Leads to the opening of K+ channels and movement of K+ out.
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.
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.
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.
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
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
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.
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.
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.
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
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.
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.
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.
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)
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.
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).
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
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
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.
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.
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.
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.
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.
Define systolic and diastolic pressure.
Systolic Pressure: Peak pressure reached in vessels.
Diastolic Pressure: Minimum pressure reached in vessels.
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.
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
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)
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.
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)
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.
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.
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
What are some key properties of GH?
Short half life of 20 minutes, also bound to protein
Pulse release
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
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
What challenges were posed to the Somatomedin Hypothesis, and what is the Dual Effector Hypothesis?
- GH injection into the growth plate stimulates growth.
- IGF antiserum injected with GH shows no growth.
- Removal of liver-derived IGF-1 (gene knockout) still results in growth.
- 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.
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.
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.
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.
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.
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.
What are the functions (5) of cortisol in fasting, and how is its release characterized?
- Promotes breakdown of muscle for gluconeogenesis.
- Exhibits a diabetogenic effect, reducing glucose uptake by muscles and adipocytes.
- Stimulates liver enzymes for amino acid conversion to glucose.
- 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
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.
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.
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).
What are the key features and mechanisms related to the mechanical structure of the lungs?
- Air-tight cavity with chest wall expansion tendency and lung collapse tendency.
- Small air gap in the pleural cavity.
Pressure Profile:
Boyle’s Law applied for flow. (PV=PV)
What are the key mechanical properties involved in respiration?
Elastic Lung and Chest Wall
Surface Tension
Compliance
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
What are transmural pressures, and how do they impact lung expansion?
Pressure across a biological membrane. (inside- outside)
Positive transmural pressure expands alveoli.
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.
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.
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.
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
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.
