big boys

Question 1

what type of tissue and what is the function of fibrous skeleton of the heart? (4)

Answer 1

• dense CT surrounds AV and outflow of vessel valves (semi-lunar valves)
• fuses together and merges with interventricular septum:
  i) supports the valves
  ii) prevents overstretching of the valves
  iii) insertion point of cardiac muscle bundles
  iv) electrical insulator between atria and ventricles - gives small delay between atria and ventricles to allow ventricles to fill before ventricles contract

Question 2

the cardiac muscle fibres form two networks from two different types of fibres.

a) what direction are the atrial fibres like? what about the ventricles?
b) how does this influence how blood moves in each ?

Answer 2

Cardiac muscle fibres form 2 networks via gap junctions at intercalated discs.

There are two types of fibres

• the atria have a circular arrangement to squash the blood down
• the ventricles have a spiralling arrangement to push the blood up and out.

These fibres are, regardless, still separated by the fibrous skeleton of the heart.

​

Question 3

explain the direction of conduction throughout the heart

Answer 3

The sino-atrial node is where the conducting system begins: natural pacemaker of the heart and is where electrical conduction will begin and spread across the atria to cause synchronous contraction.

The impulse will pause when it reaches the AV node, in order to ensure the atria have fully contracted.

The atrioventricular bundle connects the atria to the ventricles.

The AV bundle branches conduct the impulses through the interventricular septum, and the purkinjie fibres stimulate both the contractile cells of both ventricles, starting at the apex and moving superiorly

Question 4

where do you find preganglionic and postganglionic

i) sympathetic neurons
ii) parasympathetic neurons

in the heart?

Answer 4

cardioacceletory centre: medullary reticular formation

preganglionic sympathetic neurons: thoracic spinal cord
postganglionic sympathetic neurons: SA & AV node, & coronary vasuclar smooth muscle

preganglionic parasympathetic neurons: vagus nerve
postganglionic parasympathetic neurons: SA & AV node,

Question 5

explain how action potentials occur in pacemaker cells
explain how action potentials occur in ventricular cells

what determines the race of firing of cardiac pacemaker cells?

Answer 5

Pacemaker cells in the SA node

• Action potential are initiated by opening of sodium and calcium channels​
• After each action potential potassium channels (which open during the action potential) will slowly and spontaneously close.
• This causes a progressive depolarisation (pre-potential or pacemaker potential) which eventually reaches threshold for the Na+ and Ca2+ to open and a new action potential is generated

Ventricular action potentials

Ventricular muscle has an unusual shape of action potential. It starts like a normal nerve action potential with sodium influx, however this is followed by a prolonged depolarisation phase called the plateau. This plateau is due to a late and prolonged entry of calcium into the cell which helps the muscles contract for a much longer time than ordinary skeletal muscle

• **regular, spontaneous action potentials:
• specialK channels open duringAP, butslowly, spontaneously close** (aka funny current)
• causes a progressive depolarisation
• normal K channels are not present
• eventually this pacemaker / prepotential potenential reaches threshold for the Na AP channels to open: new AP generated*

- the rate of firing of pacemaker cells is determined by rate of closure of K channels

Question 6

explain the mechanism of calcium signalling driving muscle contraction in the heart

Answer 6

• depol of membrane from Na+, through Na+ channels = opens Ca 2+ channels

- Ca2+ move through calciumc channels into cell membrane

• rise in Ca2+ triggers further calcium release from the sarcoplasmic reticulum, via the ryanodine receptor
• calcium associates with troponin C in the sarcomere: calcium & troponin c exposes the myosin binding sites on the actin = allows the myosin to bind to actin

ATP hydrolyses: provides the energy to drive filament sliding

• events terminated by release of Ca2+ from sarcomere (relaxation - diastole), and reuptake into sarcoplasmic reticulum

Question 7

decribe the mechanism of excitation-contraction coupling happens in SMC

Answer 7

• rise in intracellular calcium can occur by
  i) depol of membrane opens Ca2+ channels and calcium enters
  OR
  ii) agonist induced release of calcium via IP3., through sarcoplasmic reticulum
• Calcium binds to calmodulin, which actiavtes an enzyme called myosin light chain kinase (MLCK)
• MLCK activates myosin head by phosphorylating them (ATP -> ADP + Pi, Pi attaches to the head)
• phosphorylation of myosin light chain increase ATP activity and allows myosin head groups to bind to actin & undergo cross-bridge cycling (which initiates contraction)

Question 8

explain mechanism of RBC interacting with Co2?

Answer 8

• The RBCs convert the CO2 to bicarbonate via carbonic anhydrase
• Most of the bicarbonate that is formed is expelled into the plasma and carried in the venous blood to the lungs.
• As bicarbonate diffuses out, chloride ions diffuse into the red blood cells to maintain electrical neutrality (the chloride shift)
• In the lungs, bicarbonate enters the RBCs and is converted back into C02, then released into the alveoli. Chloride leaves the red cell to balance the electrical charge of the bicarbonate leaving the cell

ALSO: BUT LESS IMPORTANT

• C02 is also carried to the lungs in the form of carbaminohaemoglobin.
• in lungs, the high partial pressure of oxygen and low pH displaces the CO2 from haemoglobin and oxyhaemoglobin is formed

Question 9

what is a consequence of exercising muscles having vasodilation?

how does the body get around to solving this?

Answer 9

• vasodilation in the active muscles reduces total peripheral resistance and would, if not compensated for, cause a drop in blood pressure.

SO

• at the start of exercise the sympathetic outflow increases.
• This produces a general vasoconstriction in the non-exercising muscles and the digestive tract
• The result is that the decrease in vascular resistance in the exercising muscles is compensated by an increase in vascular resistance in the nonactive muscles

Question 10

explain the mechanism that occurs if GFR is too low

and high :)

Answer 10

• *GFR too low**
• Cells in the macula densa of the JGA detect the concentration of sodium in the distal tubular fluid
• If Na+ levels are low, shows that GFR is too low
• The macula densa releases local chemical factors which relax the smooth muscle in the proximal tubule
• this increases the filtration pressure and GFR.
• *GFR too high**
• Cells in the macula densa of the JGA detect the concentration of sodium in the distal tubular fluid
• If Na+ levels are high, shows that GFR is too high
• The macula densa releases local chemical factors which constrict the smooth muscle in the proximal tubule
• *- decreases filtration pressure and GFR**

Question 11

explain what occurs at the loop of Henle / what is absorbed etc

a) descending loop of Henle?
b) ascedning loop of Henle?
c) distal tubule?
d) collecting duct?

Answer 11

• *As the fluid descends DLH:**
• water moves out (via aquaporins), which makes the fluid more and more concentrated because it is in equilibrium with the high concentration in the extracellular fluid in the renal medulla.
• *fluid moves up the ALH:**
• the thick ascending wall is impermeable to water
• Na+ & Cl- are pumped out of tube into extracellular space: active transport by ATP-ase
• makes the fluid v. dilute (most of Na / Cl has been removed)
• *fluid moves to distal tubule:**
• aldosterone acts to increase Na reabsorbtion (and other materials)
• *fluid moves to collecting duct:**
• fluid passes down from here to ureter and ladders
• CD has aquaporins that are opened by ADH
• if channels are open: water is reabsorbed & urine is same osmolarity as renal medullary fluid
• if channels are closed: water not reabsorbed & dilute urine produced

Question 12

what is the location, function and mechanism of action for the NKCC2 channels?

Answer 12

NKCC2 (Na-K-Cl cotransporter channel

• location: thick ascending limb of the loop of Henle
• function: to get Na / Cl out of the ascending limb and into extracellular fluid
• *- mechanism of action:**
  i) luminal walls of the epithelial cells allows sodium, potassium & chloride ions to move passively together down their concentration gradient into the cells that make thick ascending limb
  ii) then, sodium is actively transported out into extracellular space by Na/K ATP-ase
  iii) Cl- moves passively with the sodium
  iv) most of K+ ions diffuse back into the lumen via K ion channels

Question 13

which pump assists the NKCC2 pump?

explain how xix

Answer 13

Renal Outer Medullary potassium channel or ROMK (royal orders make knights)

• K+ out of the tubule cells into the lumen (where fluid is)
• generates postive voltage: 10mV in tubular lumen
• creates an overall voltage difference of 80mV between tubular lumen and tubular cell
• this voltage difference helps propel sodium via NCKK2 transporter into tubular cells

Question 14

explain the 4 reasons why oedema might occur xo

Answer 14

• *1. increased capillary hyrdostatic pressure**
• venous pressures become elevated (e.g. through gravitational forces / heart failure)
• this reduces the hydrostatic pressure gradient
• reduces reabsorbtion from interstitial fluid back into capillary
• *2. decrease in plasma oncotic pressure**
• decreases the pressure driving fluid back into capillary
• reduces reabsorbtion
• *3. increased capillary permeability**
• allows more water to leave cap
• also reduces the oncotic pressure different by allowing protein to leave the vessel more easily

4. lymphatic obstruction

Question 15

what can cause:

1. increased capillary hydrostatic pressure?
2. decrease in plasma oncotic pressure:?
3. increased capillary permeability: ?
4. secondary lymphoedema:

Answer 15

1. increased capillary hydrostatic pressure: heart failure
2. decrease in plasma oncotic pressure: hypoproteinemia (less proteins in blood). e.g. malnutririon (Kwashiorkor) or liver disease
3. increased capillary permeability: vascular damage (burns / trauma / inflammation)
4. secondary lymphoedema: surgery, elephantiasis - worm infection, tissue injury

Question 16

explain mechansim of prorenin -> angiotension II release [4]

what are differeing effects angiotension has? [4]

Answer 16

1. activation of juxtaglomerular (JG) cells cause prorenin –> renin
2. renin converts angiotensinogen into angtiotension I
3. Angiotension converting enzyme (ACE), converts angiotension I -> angiotension II
4. Angiotension II binds to either Angiotension type I or II receptors

differing effects depending on where it binds:

i) proximal tubule: Increases Na+ reabsorbtion, which increases blood flow, which increases BP
ii) adrenal cortex: increases aldosterone, which causes increase Na+ reabsorbtion in distal tubule, increase bloodflow and BP
iii) systemic arterioles: binds to GPCR = artriolar vasoconstriction = increases BP
iv) brain: stimules release of ADH = increase Na reabsorbtion

Question 17

Q

what is MOA for beta blockers for treating angina?

Answer 17

Beta Blockers

• B1 receptor antagonist:
• causes reduced HR (@ SA node)
• decrease in o2 demand at SA node
• negative inotropic effect
• decrease BP
• decreased myocardial oxygen demand

Question 18

what 3 movements happen (how) when inhalation occurs?

Answer 18

• *pump handle movement:**
• during inhalation, get elevation of the ribs: ribs move superior and anterior (increasing diameter)
• occurs at costal-vertebral joints (ribs & Tvert)
• *bucket handle movement:**
• during inhalation: increase lateral diameter of thorax
• *diaphragm**:
• during inhalation: flatttens

Question 19

what does it mean if macula dense cells detect low Na+ in distal tubule?

what happens (what is released? from where? x2) as a result of this?

Answer 19

• concentration of sodium in the distal tubule is too low = it means that the glomerular filtration rate (GFR) is too low
• causes prostaglandin E2 (PGE2) from the macula cells be released (vasodilation?)
• acts on juxtaglomerular cells to release renin in the afferent & efferent arterioles

Question 20

what happens to BP (through RAAS system) when an atheroma is formed in afferent arterioles?

Answer 20

afferent arterioles are narrowed due to atheroma formation, or some other factor which reduces blood flow into the kidney.

This will reduce GFR, more sodium will be absorbed

This will lead to a reduced sodium concentration in the distal tubule.

The JGA cells release renin, which is converted into angiotensin, which will raise blood pressure in an effort by the kidney to maintain GFR

Question 21

hat is partial pressure of o2 in alveoli?
what is partial pressure of o2 in venous blood?
what does that make the pressure gradient for oxygen to enter blood?

what is partial pressure of Co2 in alveoli?
what is partial pressure of Co2 in venous blood?
what does that make the pressure gradient for Co2 to leave blood?

Answer 21

PaO2 in alveoli: 100 mm Hg
PaO2 in venouse blood: 40 mm Hg
pressure gradient = (100-40) 60 mm Hg

PaCO2 in alveoli: 40 mm Hg
PaCO2 in venous blood: 46 mm Hg
pressure gradient = 6 mm Hg

pressure gradient for co2 is much less: changing resp. rate can alter excretion of CO2 without significantly affecting uptake of O2.

Question 22

how does blood (arterial and venous) supply occur to the nasal cavity?

Answer 22

• *Arterial supply to the nasal cavities:**
• from both the external and internal carotid arteries:
  i) branches from the external carotid artery via the maxillary and facial arteries
  ii) branches from the internal carotid artery via the ophthalmic artery
• *venous drainage:**
  i) branches to the maxillary and facial veins then drains to external jugular vein
  ii) branches to the opthalmic vein into the cavernous sinus

Question 23

how does gravity influence pulmonary circulation?

whats the 3 zone model?

Answer 23

pressure is much lower in apex c.f. base when standing:

• pulomonary artery: 15mmHg
• pulomonary base: 2 mmHg
• pulomonary apex: 25 mmHg

Creates a 3 zone model of the lung:

•The apices (zone 1) have intermittent flow; capillaries are squashed during expiration and diastole. flow occurs during systole (& inspiration)

•The centres (zone 2) have pulsatile flow; the pressure inside the capillay is greater for part of the resp. cycle: therefore is pulsatile. flow in this part of lung greater in systole than diastole; and inspiration c.f expiration

•The bases (zone 3) have continuous flow of blood; due to pulmonary A & V pressure > alveolar pressure

Question 24

what is difference in compliance in base v apex of the lung? what does this mean for ventilation in apex and base?

Answer 24

Compliance in base: higher - this means the base of the lungs are better ventilated (per unit lung volume) than apices.

Compliance in apex: lower

The basal alveoli are more ventilated than apical alveoli, as they have a higher compliance (as shown by a steeper sloping in the curve) and thus a bigger volume change per unit pressure change

Question 25

what is the mechanism of pulmonary arterial vasodilation during exercise? 1. in the apex of the lung? 2. in the base of the lung?

Answer 25

**in the apex of the lung:** - A small pressure increase in pulmonary arterial pressure produces a disproportionately large increase in blood flow. - The pulmonary arterioles in zone 1 become distended (stretched) when the pressure in them rises: This stretching generates a reflex extra relaxation of the arterial smooth muscle and so the vessels enlarge , reducing the vascular resistance and increasing the flow through zone 1. Blood flow through zone 1 can increase seven to eight fold during exercise A similar reflex stretch induced relaxation occurs in zone 2 and 3, where blood flow can increase 2 to three times * *in the base of the lung:** - normal base alveoli in the lungs are relatively poorly ventilated during quiet breathing. Thus the associated capillaries are constricted. - The increased ventilation that occurs at the start of exercise: increases PO2 in these alveoli. - This dilates the associated capillaries and thus reduces total pulmonary vascular resistance Reveal Answer

Question 26

explain the different phases of cardiac (myocardium) excitation occurs

Answer 26

* *_Phase 4: The resting phase_** - resting potential: **−90 mV** due to a constant **outward leak of K+ through** inward rectifier channels. * *- Na+ and Ca2**+ **channels** are **closed** at resting TMP. * *_Phase 0: Depolarization_** - An action potential triggered in a neighbouring cardiomyocyte or pacemaker cell causes the TMP to **rise above −90 mV.** - **Fast Na+ channels start to open** one by one and Na+ leaks into the cell, further raising the TMP. - TMP approaches −**70mV**, the **threshold potential** in cardiomyocytes, i.e. the point at which enough fast Na+ channels have opened to generate a self-sustaining inward Na+ current. - The large Na+ current **rapidly depolarizes** the TMP to 0 mV and slightly above 0 mV for a transient period of time called the overshoot; **fast Na+ channels clo**se (recall that fast Na+ channels are time-dependent). - L-type (“long-opening”) Ca2+ channels open when the TMP is greater than −40 mV and cause a small but steady influx of Ca2+ down its concentration gradient. **_Phase 1: Early repolarization_** TMP is now slightly positive. Some **K+ channels open briefly** and an **outward flow of K+ returns** the TMP to approximately 0 mV. **_Phase 2: The plateau phase_** L-type **Ca2+ channels are still open** and there is a small, **constant inward current of Ca2+.** This becomes **significant** in the **excitation-contraction coupling** process. **K+ leaks out down** its concentration gradient through delayed rectifier K+ channels. These two **countercurrents are electrically balanced,** and the TMP is maintained at a plateau just below 0 mV throughout phase 2. **_Phase 3: Repolarization_** **Ca2+ channels are gradually inactivated.** Persistent **outflow of K+,** now **exceeding** Ca2+ inflow, brings TMP back towards resting potential of −90 mV to prepare the cell for a new cycle of depolarization.

Question 27

how do action pacemaker cells, like the SA node and AV node create different action potentials compared to cardiomyocytes?

Answer 27

_at cell in SAN Node:_ - Na/K pump: 3 Na out/ 2 in. creates -5mV outside cell, - K+ leaks out of the cell - Ca2+ leaks into cell - Na leaks into the cell = creates a wondering baseline of positive increase in charge, until reaches **-40mv:** - more Ca2+ channels open and come into cell, depolarisng the cell. when reaches **+20mV** more K+ channels open: repolarise the cell repeat process.

Question 28

explain the conduction signal of the heart [3]

Answer 28

**SA Node:** releases electrical stimuli at a regular rate Each stimulus passes through the myocardial cells of the **atria creating a wave of contraction which spreads rapidly through both atria.** The electrical stimulus from the **SA node eventually reaches the AV node** and is **delayed** briefly so that the contracting atria have enough time to pump all the blood into the ventricles Electrical stimulus **passes through the AV node and Bundle of His into the Bundle branches and Purkinje fibres** Causes the ventricles to contract

Question 29

explain the Hering-Breuer reflex

Answer 29

Afferent information from stretch receptors in the lungs is transmitted to the brainstem via the vagus nerve to signal the extent of lung inflation as part of a protective negative feedback control mechanism that serves to prevent overinflation of the lungs. Prolonged inspiration and thoracic expansion activates, slowly adapting pulmonary stretch receptors. These receptors relay a signal through the vagus nerve (on a breath-by-breath basis) to "pump" cells" These pump cells receive these vagal inputs and project the information to the medullary post-inspiratory neurons.[22] These neurons subsequently project inhibitory signals back to the inspiratory neurons along the lateral portion of the respiratory column, thereby terminating inspiration and beginning a prolonged expiration.[23][24][25][26]