W28 L1&2 - Circulation and Respiration

what is the systemic circulation

left side of heart → tissues → right side heart

arterial system: left ventricle → aorta → arteries → arterioles → branch capillaries

what is pulmonary circulation

right ventricle → lungs → left ventricle

where does the blood go once it has reached the capillaries

venus system: small vessels → venules → veins → Vena cava → RHS

what is cardiac output

total blood flow

where does exchange of material take place, why

capillaries

because they have a leaky epithelium which allows the exchange of materials

what can’t capillaries control, why

can’t control blood flow because they don’t have much smooth muscle in their walls

what allows arteriole movement

smooth muscle in their wall allows them to constrict and dilate

• means they can have variable resistance to blood flow

  • can distribute blood across different tissues by selectively constricting and dilating

which end connects capillaries to the venus system

at the distal end of capillaries, blood flows into the venous side of circulation

what important function do veins have

act as a volume reservoir

• if blood pressure falls to low, allow blood to be sent to arterial side to increase bp

describe the composition of 5 blood vessels

Artery

diameter 0.1 -10+ mm

mean wall thickness - 1mm

composition - small amount of endothelium, lots elastic tissue and more smooth muscle, some fibrous tissue

Arteriole

diameter 10-100 micrometers

mean wall thickness - 6 micrometers

composition - small amount of endothelium, no elastic tissue, some smooth muscle, no fibrous tissue

Capillary

diameter 4 -10 micrometers

mean wall thickness - 0.5 micrometers

composition - small amount of endothelium

Venule

diameter 10 - 100 micrometers

mean wall thickness - 1 micrometer

composition - small amount of endothelium, some fibrous tissue

Vein

diameter 0.1 -100+ mm

mean wall thickness - 0.5mm

composition - small amount of endothelium, some elastic tissue and more smooth muscle, some fibrous tissue

what is the composition of blood vessels like generally

• inner lining is a thin layer of endothelial cells that secrete paracrine signals

• walls

  • elastic tissue - connective tissue elasticity (endothelial layer + adjacent elastic tissue = tunica intima)

  • vascular smooth muscle - arranged in circular or spiral layers. contractions depends on Ca2+ entry. most bv smooth muscles maintain partial state of contraction - muscle tone influenced by signal molecules (hormones, neurotransmitters)

  • fibrous tissue - connective tissue, stiffness

how is the pressure maintained in the circulatory system

pressure stored in the elastic walls of the arteries and contained by stiffness of fibrous tissue

what can the arteriole walls do, under the influence of what

arteriole walls can contract and relax under the influence of chemical signals

what are capillaries made from, because of this what do they have

consist of one flat layer of endothelium, one cell thick, so are supported on an extracellular matrix - the basal lamina

what are pericytes

highly branched contractile cells wrapped around the capillaries which contribute to the tightness/leakiness of capillaries

which cells help to control the blood flow through capillaries

pericytes - contractile cells which wrap around the capillaries

how does blood flow back from microcirculation and the venus system

• blood flows from capillaries into venules

  • they are distinguished from capillaries by their convergent pattern of flow

• blood flows from venules to veins

• some veins have one way valves to prevent backflow

• veins have thinner walls than arteries, with less elastic tissue and expand easily

• veins more numerous than arteries, larger diameter, hold more blood, lie close to body surface

• skeletal muscle pressure on veins can help force blood up and valves then stop it from going back

cellular vs external respiration

cellular - intracellular reaction

external - movement of gasses between the environment and the body’s cells

what is the respiratory tract divided into

upper and lower regions

• lower tract also called the thoracic portion

Upper

• mouth

• nasal cavity

• pharynx

• larynx

Lower

• trachea

• 2 primary bronchi

• their branches

• lungs

what does pleural fluid do and where is it

• lowers friction between membranes

• holds lungs tight against thoracic wall

found between pleural membranes

what is pleurisy

inflammation of the pleura

• makes breathing laboured

• usually caused by another condition e.g infection

what is pleural effusion

when pleural fluid accumulates

• e.g TB, also when body fluid volumes are disturbed

importance of ciliated epithelium cells in the airway

allow movement of mucus (secreted by goblet cells) up towards the pharynx and remove any trapped pathogens or any trapped particulate

what can occur within ciliated epithelium cells

sub mucosal glands

what are the types of alveolar cells and what do they do

type I - gas exchange

type II - produce surfactant

what condition can lead to a change in mucus consistency

cystic fibrosis

• a failure of the CFTR receptor leads to thick, sticky mucus that causes the deep diseases pathology seen in CF

what are the two types of breathing

quiet (passive) breathing

• normal breathing requires very little muscle contraction

• diaphragm is the dominant muscle involved in quiet respiration

forced (active) breathing

• deeper breathing due to increased physical activity

• also deliberate breath control (singing, inflating a balloon)

• several muscles involved in forced inspiration and expiration

what is the inner lining of the blood vessels called

endothelium

which muscles are used for quiet expiration

diaphragm

what are anatomical aspects which impact lung function/breathing

• lungs (bronchi, bronchioles, alveoli)

• chest cavity (ribs, intercostal muscles) and the diaphragm muscle

• pleural membranes (pleural fluids and pleural pressure)

what are functional aspects which impact lung function/breathing

• passive (shallow) breathing - lung elasticity (recoil), pressure gradients

• active (deep) breathing - different muscles involved larger tidal volumes up to vital capacity (maximum)

when does inspiration occur

when alveolar pressure decreases

explain what is occuring in this image

ventilation

time 0 - when pressures are equal there is no air flow

time 0-2 - inspiration

time 2-4 - expiration (occurs when alveolar pressure increases)

time 4 - passive vs active respiration

is pulmonary ventilation or alveolar ventilation great

which one is a better indication of how much fresh air reaches the alveoli

pulmonary ventilation is greater because of dead space

alveolar ventilation is better because fresh air remaining in the dead space does not get to the alveoli

what is dead space

Dead space (Vd) is the portion of each tidal volume that does not take part in gas exchange and includes:

• anatomical dead space (Vd_aw), that is the part of airways that do not contribute to gas exchange (nose, pharynx, conduction airways

• (Vd_alv) alveoli which are well-ventilated but poorly perfused

how can lung function be measured

using a spirometer

• when patient breathes in, air moves into the lungs, the volume of the bell decreases, the pen rises on the tracing

define tidal volume

the amount of air moved in or out of the lungs at rest (i.e. quiet/passive/shallow breathing)

• ~500ml

define expiratory reserve volume (ERV)

the extra volume of air that can be forcibly blow out of the lungs, additional to that exhaled in the tidal volume

what is inspiratory reserve volume (IRV)

the extra volume of air that can be forcibly sucked into the lungs, additional to that normally inhaled in tidal volume

what is vital capacity

the total volume of air that can be breathed in and out of the lungs

• TV+ERV+IRV

how to measure capacities

• inspiratory capacity

• vital capacity

• total lung capacity

• functional residual capacity

lung values of men and women

• IRV

• TV

• ERV

• VC

• RV

• TLC

IRV

men - 3000

women - 1900

Tidal Volume

men - 500

women - 500

ERV

men - 1100

women - 700

Vital Capacity

men - 4600

women - 3100

Residual volume

men - 1200

women - 1100

Total lung capacity

men - 5800mL average 70kg man 28yr

women - 4200mL average 50kg woman 28yr

what two important measures are used to monitor lung function

• forced vital capacity (FVC)

  • the total amount of air that you blow out in one deep breath

  • FVC varies with age, weight, sex, etc but most significantly can be reduced in disease

• forced expiratory volume in 1 sec (FEV1)

  • the amount of air you can blow out within one second

what is the diversity in lung capacity like

well documented that there are differences by ethnicity and geographic location

• much debate as to reasons for this

• it changes even more in children

• within India (well cited example) can be significant differences between ethnicities

  • for this reason hard to give one set of standards

COVID-19 highlighted issue of diversity h

which lung volume cannot be directly measured

residual volume

what is hypoxia

too little oxygen

what is hypercania

increased conc in CO2

how can the body avoid hypoxia and hypercania

regulate

• oxygen

• carbon dioxide

• pH

give a brief overview of gas exchange

• oxygen enters blood at alveolar-capillary interface

• oxygen is transported in blood dissolved in plasma or bound to haemoglobin inside RBCs

• oxygen diffuses into cells

• CO2 diffuses out of cells

• CO2 is transported as dissolved, bound to haemoglobin, or as HCO₃^-

• CO₂ enters alveoli at alveolar-capillary interface

what do individual gases diffuse along during ventilation

what does the total pressure of mixed gas equal to

they diffuse along partial pressure gradients until equilibrium

• total pressure of mixed gas = sum of particle pressures of individual gases

gas exchange between alveoli and blood

what is the partial pressure like of alveolar air compared to that of blood

what does this mean

P_O2 of alveolar air is higher than the P_O2 of blood

• means diffusion will occur towards the blood

gas exchange between blood and tissues

what is the partial pressure like of the blood compared to the tissues

what does this mean

P_O2 of blood is higher than P_O2 of tissues

• means diffusion will occur towards the tissues

How does gas solubility affect oxygen and carbon dioxide transport between alveoli and blood?

• Oxygen has low solubility in water, so at equilibrium, its concentration in liquid remains much lower despite equal partial pressures.

• Carbon dioxide is more soluble, meaning more CO₂ dissolves in liquid at the same partial pressure.

• Unlike solids, gases like oxygen are more soluble in cold water than in warm water.

• Since blood is warm, oxygen's lower solubility and CO₂'s higher solubility impact how they are transported in the bloodstream.

  • Oxygen (O₂) Transport:

    • Poorly soluble in plasma → only ~2% dissolves.

    • ~98% binds to haemoglobin in red blood cells for transport.

  • Carbon Dioxide (CO₂) Transport:

    • More soluble than O₂ → ~7-10% dissolves in plasma.

    • ~20-30% binds to hemoglobin as carbaminohemoglobin.

    • ~60-70% is converted to bicarbonate (HCO₃⁻) for transport.

  • Impact on Gas Exchange:

    • In the lungs, O₂ binds to haemoglobin, and CO₂ is released for exhalation.

    • In the tissues, O₂ is released, and CO₂ is picked up for transport back to the lungs.

what is the partial pressure of oxygen and carbon dioxide throughout gas exchange

• Dry Air

  • PO₂ ≈ 160 mmHg

  • PCO₂​ ≈ 0.25 mmHg

• Inhaled air (Alveoli):

  • PO₂ ≈ 100 mmHg

  • PCO₂​ ≈ 40 mmHg

• Arterial Blood (Leaving Lungs):

  • PO₂ ≈ 100 mmHg (matches alveoli, fully oxygenated)

  • PCO₂​​ ≈ 40 mmHg

• Tissues (Oxygen Delivery & CO₂ Pickup):

  • PO₂​​ ≈ 40 mmHg (lower due to cellular respiration)

  • PCO_2​​ ≈ 45 mmHg (higher due to metabolism)

• Venous Blood (Returning to Lungs):

  • PO₂​​ ≈ 40 mmHg (deoxygenated)

  • PCO₂​​ ≈ 45 mmHg

if plasma pH increases from 7.40 to 7.48m haemoglobin’s affinity for oxygen will … so … oxygen will be released to the tissue

increased, less

How does haemoglobin help transport oxygen in the blood?

• Oxygen (O₂) first dissolves in plasma but accounts for <2% of total O₂ in blood

  • O2 not good at dissolving in liquids so haemoglobin helps transport around body

• Haemoglobin (Hb) binds O₂ to form oxyhemoglobin (HbO₂).

• Reaction: Hb + O₂ ⇌ HbO₂ (oxyhemoglobin).

• Each haemoglobin molecule has 4 heme groups, allowing it to bind 4 O₂ molecules.

• >98% of O₂ is transported by haemoglobin to tissues.

what protein helps increase movement of O2 into plasma

haemoglobin essentially sequesters O2 out of the plasma so that more can move from the alveoli into the plasma

• wouldn’t get enough oxygen to our tissues if it was left to just being in the plasma

How does haemoglobin increase oxygen-carrying capacity in the blood?

• Without haemoglobin:

  • O₂ dissolves in plasma, carrying only 3 mL O₂/L blood.

  • no O2 in RBC

• With haemoglobin (at normal PO₂):

  • Haemoglobin binds 98% of O₂, increasing total O₂ transport to 200 mL O₂/L blood.

    • 3mL O2/L in blood in plasma

    • 197mL O2/L in blood in RBC

• At reduced PO₂​​ (e.g., in tissues):

  • Haemoglobin releases some O₂, reducing carrying capacity to 100.3 mL O₂/L blood.

    • 0.8mL O2/L in blood in plasma

    • 99.5mL O2/L in blood in RBC

• Key Concept: Hemoglobin vastly increases O₂ transport beyond plasma solubility limits and releases O₂ where needed.

what factors affect the binding of haemoglobin to oxygen

• Partial Pressure of Oxygen ( PO₂ ):

  • Higher PO₂ (lungs) → More O₂ binds to hemoglobin (HbO₂ formation).

  • Lower PO₂​​ (tissues) → O₂ is released for cellular use.

• pH (Bohr Effect):

  • Low pH (acidic, ↑CO₂, ↑H⁺) → O₂ unloads more easily (right shift in curve).

  • High pH (alkaline) → Hb holds onto O₂ more tightly (left shift).

• Carbon Dioxide (CO₂) Levels:

  • ↑ CO₂ lowers pH and promotes O₂ release.

  • ↓ CO₂ raises pH, increasing O₂ binding.

• Temperature:

  • ↑ Temperature (active tissues) → More O₂ is released (right shift).

  • ↓ Temperature (lungs) → More O₂ binds (left shift).

what is cooperative binding

• what happens in the reverse of this

• The binding of the first oxygen molecule results in a conformational change in the structure of the haemoglobin molecule, making it easier for each successive oxygen molecule to bind

  • 4 polypeptides in Hb

  • s shape curve of graph shows cooperativity - not linear

• The reverse of this process happens when oxygen dissociates in the tissues

• compared with other ways for this protein to work, the cooperative binding allows release of more oxygen at tissues and good binding in the lungs

give a brief overview of carbon dioxide transport

1. CO₂ diffuses out of cells into systemic capillaries

2. only 7% of the CO₂ remains dissolved in the plasma

3. nearly a fourth of the CO₂ binds to haemoglobin, forming carbaminohaemoglobin

4. 70% of the CO₂ is converted to bicarbonate and H⁺

   • Haemoglobin buffers H⁺

5. HCO₃^- enters the plasma in exchange for the Cl^- (the chloride shift)

6. at the lungs, dissolved CO₂ diffuses out of the plasma

7. by the law of mass action, CO₂ unbinds from haemoglobin and diffuses out of the RBC

8. the carbonic acid reaction reverses, pulling HCO₃^- back into theRBC and converting it back to CO₂

the oxygen-Hb dissociation curve shifts to the right in response to

• ↓ pH (Bohr Effect) → More H⁺ ions (acidic conditions) reduce Hb's O₂ affinity.

• ↑ CO₂ Levels → Forms carbonic acid, lowering pH and promoting O₂ unloading.

• ↑ Temperature → Metabolically active tissues need more O₂.

A right shift means better O₂ delivery to tissues under conditions of high demand.