FOUNDATIONS: RESPIRATORY

SYSTEM, FLUID BALANCE, BLOOD

DISORDERS

ORGANISERS OF THE GEP CRASH COURSE SERIES:

• ACHVINI SRI – F1 DOCTOR
• ANEYA SCOTT – F1 DOCTOR
Tips for getting through the first module!

• Focus on understanding the key concepts and the basics

• First experience approaching patient

• How to take a good history and present it back to the doctor

• Helps to try start from scratch

• Everything you come across in this module will be revisited later

INTRODUCTION TO THE RESPIRATORY SYSTEM

ACHVINI SRI – F1 DOCTOR

achvini_s@outlook.com
Quick Anatomy
• Key points to note:
• Gas exchange occurs at
the level of the alveoli
• Gas exchange occurs
along a concentration
gradient for oxygen and
carbon dioxide
Which gas is the most
abundant in the air?
A) Oxygen
B) Nitrogen
C) Carbon dioxide
D) Argon
E) Sulphur dioxide
Which gas is the most
abundant in the air?
A) Oxygen
B) Nitrogen
C) Carbon dioxide
D) Argon
E) Sulphur dioxide
Key concepts
• Diffusion
• Passive movement of molecules from high to low
concentration down a concentration gradient
• Partial pressure of gases
• In a mixture of gases, each gas exerts its own
partial pressure
• Dalton’s law: sum of partial pressures = total
pressure of mixture
• Transport of CO2
• Mostly as bicarbonate
• Rest dissolved in plasma or bound to Hb
• Composition of room air:
• 78% Nitrogen
• 21% Oxygen
• 1% other gasses including CO2
Cellular respiration

• Cellular respiration
• Process of converting nutrients such as glucose into ATP
(energy)
• Requires oxygen to work
• Electron transport chain
• Main source of ATP production (32 molecules per
glucose)
• ATP produced via oxidative phosphorylation (reducing
NADH and FADH with oxygen)
• CO and other toxins can interfere with this process
Which conditions will lead to a
right-shift in the oxygen
haemoglobin dissociation
curve? i.e. decrease Hb’s
affinity for oxygen A) High CO2, low pH, high temp

B) Low CO2, low pH, high temp

C) High CO2, low pH, low temp

D) High CO2, high pH, high temp

E) Low CO2, high pH, high temp

Which conditions will lead to a
right-shift in the oxygen
haemoglobin dissociation
curve? i.e. decrease Hb’s
affinity for oxygen A) High CO2, low pH, high temp

B) Low CO2, low pH, high temp

C) High CO2, low pH, low temp

D) High CO2, high pH, high temp

E) Low CO2, high pH, high temp

Oxygen transport

• Structure and function of Hb

• Made up of 2 alpha, 2 beta and 4 haem
groups (porphyrin and Fe2+ ion)
• Each haem binds one oxygen molecule
• Each Hb binds 4 in total
• Oxygen dissociation curve
• Reflects changeable Hb affinity for oxygen
• When oxygen binds – Hb undergoes
conformational change and increases
affinity
• Affinity falls as Hb becomes more
saturated
Carbon monoxide on oxygen transport
• Carbon monoxide binds irreversibly to
Hb’s haem groups. This uses up heme
groups that could have picked up O2.
• CO also reduces Hb’s affinity for
oxygen – even if there are heme
groups still spare, O2 won’t be picked
up
• CO therefore reduces Hb’s oxygen
carrying capacity and can lead to
hypoxia
• Note that there are still lots of O2
molecules in the bloodstream – they
just can’t bind to Hb
Further action of carbon monoxide

• Carbon monoxide (CO)

doesn’t just occupy heme
groups – it actually inhibits
respiration on a deeper
cellular level.
• It binds to mitochondrial
cytochrome C oxidase
(complex IV) in the electron
transport chain and inhibits
respiration – and the
production of ATP
 The Vital Signs and Bloods in CO poisoning

• Clinical presentation: Investigations Results

pH 7.32 (7.35-7.45)
• Consciousness (AVPU)
pO2 12kPa (12-15kPa)
• BP, HR, RR, Temp
pCO2 4.1kPa (4.5-6.1kPa)
• Pain?
HCO3- 19mmol/L (22-26mmol/L)
• Meds/substances?
Oxyhaemoglobin 59% (94-100%)
• Smoking/Alcohol Carboxyhaemoglobi 38% (smokers: 2-9%
n depending on how much
smoked)
 THANK YOU! ☺
Topics not covered:
• Detailed structure of airway

Please fill in the feedback form for access

to the SBAs! Thank you! Questions?
INTRODUCTION TO FLUID BALANCE
ACHVINI SRI – F1 DOCTOR
achvini_s@outlook.com
You are out for drinks with your
friends. Your mind wonders off
thinking about fluid balance in
the body.
A) 20%
Roughly, what percentage of
the body is made up of water? B) 40%
C) 45%
D) 60%
E) 75%
You are out for drinks with your
friends. Your mind wonders off
thinking about fluid balance in
the body.
A) 20%
Roughly, what percentage of
the body is made up of water? B) 40%
C) 45%
D) 60%
E) 75%
You continue drifting off in your
thoughts about fluid balance.
You wonder, on average what
percentage of fluid output is A) 5%
due to metabolism?
B) 10%
C) 15%
D) 20%
E) 25%
You continue drifting off in your
thoughts about fluid balance.
You wonder, on average what
percentage of fluid output is A) 5%
due to metabolism?
B) 10%
C) 15%
D) 20%
E) 25%
Fluid Compartments
• Key points
• IC fluids – inside the cells
e.g. cytoplasm
• EC fluids – outside the cells
e.g. plasma and interstitial
fluid
Fluid input/output
You are now a medical student
on placement. It’s been a slow
day so your F1 decides to start
quizzing you to entertain
themself. A) Na+
He asks you: B) K+
‘Which ion is the most C) Cl-
prevalent extracellularly?’
D) Ca2+
E) HCO3-
You are now a medical student
on placement. It’s been a slow
day so your F1 decides to start
quizzing you to entertain
themself. A) Na+
He asks you: B) K+
‘Which ion is the most C) Cl-
prevalent extracellularly?’
D) Ca2+
E) HCO3-
Composition of body fluids
• Major Ions
• Intracellular: K+
• Extracellular: Na+ and Cl-
Osmotic and hydrostatic pressures
• Osmotic pressure – the pressure on a solution to prevent fluid
movement, dictated by the solute particles.
• Hydrostatic pressure – the pressure exerted by fluids.

• Key in allowing exchange of fluids between IC and EC compartments.

• Alterations in solute concentrations leads to movement of water.

Osmolality – the amount of

solute in a solution.
Movement of water across cell membrane
Movement of water across cell membrane
• Water follow solutes in a solution
across a semi-permeable membrane.
• Effectively to moves to area of high
concentration of solute to make it move
dilute.

• Change in osmotic pressure due to

movement of water can affect blood
pressure.
• And can affect vital signs.
25 year old female comes into
hospital following multiple
episodes of watery diarrhoea
after eating take out from a
local restaurant. A) Loss of Na+ ions from ECF
She has signs and symptoms B) Loss of Cl – ions from ECF
indicating dehydration.
C) Loss of K+ ions from ECF
What do you think is the
mechanism underlying the D) None of the above
dehydration.
E) All of the above
25 year old female comes into
hospital following multiple
episodes of watery diarrhoea
after eating take out from a
local restaurant. A) Loss of Na+ ions from ECF
She has signs and symptoms B) Loss of Cl – ions from ECF
indicating dehydration.
C) Loss of K+ ions from ECF
What do you think is the
mechanism underlying the D) None of the above
dehydration.
E) All of the above
 Watery Diarrhoea
• Certain bacteria alter the behaviour of the ion Obs/Ix Results

channels on the cells lining the intestines Pulse rate 110bpm (60-100bpm)
Blood pressure 100/65 lying; 80/55 standing
• Can upregulate ion channels leading to secretion (120/80) - postural hypertension
of ions from the cells into intestinal lumen Na+ 143mmol/L (137-143mmol/L)
• Leads to increase ion concentration in lumen Urea 20mmol/L (3.0-8.0mmol/L)
• ECF fluids move into lumen along concentration
gradient
• Leads to watery diarrhoea
• Plasma volume decreases
• ECF becomes more concentrated than ICF leading
to fluid to shift along concentration gradient
• Cells lose water and become shrivelled
• Without fluid replacement – 🡫 cell function
• Eventual death from dehydration
 THANK YOU! ☺
Topics not covered:
• Structure of kidney and nephron
• Chemical transmission and drug
action

Please fill in the feedback form for access

to the SBAs! Thank you! Questions?
Sickle Cell
Aneya Scott
FY1 Doctor
Anaemia – Signs and Symptoms
Definition:
Condition in which the haemoglobin concentration is lower
than normal (<120 g/L in females and <140 g/L in males)

Symptoms:
• Pallor
• Fatigue
• Breathlessness
• Palpitations
• Koilonychia
• Angular stomatitis
• Glossitis
Causes of anaemia
Pathophysiology approach

Failure of Production Failure of appropriate utilization Increased Destruction/Loss

B12/Folate/Iron Deficiency Anaemia of chronic disease Blood loss – heavy periods, GI bleeds,
EPO deficiency in CKD trauma
Bone marrow failure Haemolysis – SC, thalassaemia

Size of the cells approach

Microcytic (MCV <80) Normocytic (MCV 80-100) Macrocytic (MCV>100)

Iron Deficiency Anaemia Anaemia of chronic disease Folate Deficiency

Thalassaemia (early) Alcohol
Anaemia of chronic disease Aplasia Thyroid
(late) Chronic renal failure Reticulocytosis
B12 Deficiency
Cytotoxic Drugs
 You are on placement in
GP when a 30 y/o lady
comes into the surgery
complaining of feeling A) Low MCV, High Ferritin, High TIBC
tired all the time and
getting breathless when B) High MCV, Low Ferritin, Low TIBC
walking up the stairs. On
further questioning, she C) Low MCV, Low Ferritin, High TIBC
tells you she has been D) High MCV, High Ferritin, Low TIBC
having particularly heavy
and long periods recently. E) Low MCV, Low Ferritin, Low TIBC
What would you expect
to see on her blood
tests?
 You are on placement in
GP when a 30 y/o lady
comes into the surgery
complaining of feeling A) Low MCV, High Ferritin, High TIBC
tired all the time and
getting breathless when B) High MCV, Low Ferritin, Low TIBC
walking up the stairs. On
further questioning, she C) Low MCV, Low Ferritin, High TIBC
tells you she has been D) High MCV, High Ferritin, Low TIBC
having particularly heavy
and long periods recently. E) Low MCV, Low Ferritin, Low TIBC
What would you expect
to see on her blood
tests?
Blood components Water
Ions
Proteins
Gases
Wastes
Nutrients

Lymphocytes
Monocytes
Neutrophils
Basophils
Eosinophils
 Haemoglobin

~250 million Hb molecules per RBC

1 RBC can carry up to 1 billion oxygen molecules

Types
•2⍺2β = HbA (95-98% in adults)
•2⍺2γ = HbF (2-4% in adults)
•2⍺2δ = HbA2 (0.8-2% in adults)
 A) Primary
What type of
B) Secondary
protein C) Tertiary
structure is D) Quaternary
haemoglobin? E) Quinary
 A) Primary
What type of
B) Secondary
protein C) Tertiary
structure is D) Quaternary
haemoglobin? E) Quinary
 Sickle Cell - Pathophysiology

Due to a point mutation on the beta globin gene – located on

chromosome 11
Amino acid substitution 🡪 Glutamic acid swapped for Valine
Deoxygenated HbS polymerises more easily

Life span of a sickle RBC 🡪 17 days

Signs/Symptoms derived from:

1. Haemolysis
2. Vaso-occlusive phenomena
 Conditions/
Environments
that cause
‘sickling’ to
occur
 Conditions/
Environments 1. Cold

that cause 2. Hypoxia

3. Dehydration
‘sickling’ to 4. Acidosis
5. Infection
occur
 Sickle Cell
Complications
 Encapsulated organisms:
Some – Salmonella

The Spleen
Killers - Klebsiella
Have – Haemophilus influenza type B
Pretty – Pseudomonas aeruginosa
Nice – Neisseria meningitidis
Evasive – E. Coli
Functions of the spleen ‘FISH’: Structured – Streptococcus pneumoniae
Capsules – Cryptococcus neoformans
• Filtration of encapsulated organisms and blood cells
• Immunological function (produces lymphocytes in
newborns)
• Storage of blood
• Haematopoiesis in the foetus
 Sickle Cell Management
Patient Education General Care Managing Acute
• Folate supplements Complications
• Immunisations • Analgesia
• Antibiotic prophylaxis
• Fluids
• Exchange transfusions

Preventing vaso-occlusive Managing Chronic Curative Treatment

phenomena Complications • Haematopoietic stem cell
• Top up transfusions • Iron chelators transplants (rare)
• Exchange transfusions
• Hydroxycarbamide/hydroxyurea
 Thalassaemia
Severe reduction/absent production of
either beta or alpha globin chains.

Types:
• Beta thalassaemia
• major, intermedia, trait
• Alpha thalassaemia
 Beta Thalassaemia
Major
• Problem with chromosome 11 results in no production of
beta globin – raised HbA2 and HbF to compensate
• Presents in childhood with hepatosplenomegaly, anaemia
(microcytic), faltering growth
• More common in Indians, Mediterranean and people from
Middle East
• Chronic haemolytic anaemia and ineffective haematopoiesis
• Extramedullary haematopoiesis prevented by transfusions –
hepatosplenomegaly, bone marrow expansion – maxillary
overgrowth and skull bossing, osteoporosis

Management:
• Lifelong transfusions – can cause iron overload
• Iron chelators
 • Haematology is great ☺ you get to do lots more in T year

Other things to cover in this week:

• Recap oxygen dissociation curve
• Haematopoeisis
• Types of bacteria – gram negative/positive etc

In Summary: Thanks for listening!