GEP (Foundation Module) Week 3

Question 1

Identify the anatomy of the heart?

Answer 1

Question 2

What does the Brachiocephalic trunk bifurcate into?

Answer 2

The brachiocephalic trunk bifurcates into the right subclavein artery and the right common carotid artery.

Question 3

what does the Common carotid artery bifurcate into?

Answer 3

• It splits into an external carotid artery (Supplies neck and outside of cranium).
• internal carotid artery (supplies the inside of cranium).

Question 4

What does the subclavian artery become after passing what anatomical border?

Answer 4

The subclavian artery becomes the axillary artery after passing the lateral border of the first rib.

Question 5

What does the axillary artery give rise to at what anatomical border?

Answer 5

The axillary artery gives rise to the brachial artery at the inferior border of teres major muscle.

Question 6

What does the brachial artery bifurcate into?

Answer 6

The brachial artery bifurcates into the radial and ulnar artery

Question 7

What does the thoracic aorta become as it travels down and what does it bifurcate into?

Answer 7

The thoracic aorta becomes the abdominal aorta and birfurcates into the right and left common iliac artery.

Question 8

What doe the common iliac artery bifurcate into?

Answer 8

It birfucates into Internal and external iliac artery.

Question 9

What does the external iliac artery become and at what anatomical border?

Answer 9

The external iliac artery runs under the inguinal ligament at the top of the lower limb. At this point, it becomes the femoral artery.

The deep femoral artery arises close to the begininning of the femoral artery.

Question 10

What does the femoral artery become?

Answer 10

At the distal part of the thigh, the femoral artery becomes the popliteal artery which runs behind the knee.

Question 11

What does the popliteal artery give rise to?

Answer 11

The popliteal artery gives rise to the anterior and posterior tibial artery.

Question 12

What is DNA

Answer 12

Deoxyribonucleic acid and are made up of nucleotides. Each nucleotides containing a phosphate group, a sugar group and a nitrogenous base.

Question 13

What are the nitrogenous bases of DNA?

Answer 13

• Purine group: A (Adenine), G (Guanine)
• Pyrimidines: C (Cytosine), T (Thymine)

Question 14

What is a codon?

Answer 14

A codon is sequence of 3 bases and each codon codes for a particular amino acid.

As there are 4 bases and 43 different ways to arrange the bases, it produces 64 codons.
As there are 20 different common amino acid it allows a codon for each.

Question 15

How does protien synthesis occur?

Answer 15

1. RNA polymerase unzips DNA in nucleus
   Get the editing, splicing, capping (all transcription)
2. mRNA leaves nucleus
   3.Translation ribosome comes along to make protein w/ tRNA codons.
   4.Protein starts to fold after it has finished forming

Question 16

What are the types of protien structures?

Answer 16

1. Primary structure
2. secondary structure (beta pleated sheets/alpha helix)
3. tertiary structure
4. quaternary structure

Question 17

What are the different types of mutations that can happen in codons?

Answer 17

Frameshift insertion/deletion
Conservative, functioning
Non-conservative, non-functioning

Question 18

Functions of Blood?

Answer 18

transport (e.g., oxygen, hormones, and glucose),

immunity (e.g., leukocytes),

haemostasis (= stopping blood loss), and

thermoregulation (blood carries heat).

Question 19

What is the composition of Blood?

Answer 19

Question 20

How are Red blood cells formed (Erythrocyte) also know as Erythropoiesis?

Answer 20

Main Points:
when the nucleus is ejected from one of the precursor cells, the resultant cell is known as a reticulocyte;

reticulocytes retain some organelles;

the reticulocytes leave the bone marrow and circulate in the blood for about one or two days. As they do, the organelles disappear, and at that point, it is a mature erythrocyte.

Question 21

Describe the regulation of Erythropoiesis?

Answer 21

Erythropoietin (EPO) is a hormone that is secreted by the kidneys.

↓ O2 → detected by kidneys → ↑ synthesis of EPO → EPO released by the kidneys.

EPO acts on bone marrow to increase RBC production.

More RBCs in circulation → ↑ O2 concentration in the blood.

↓ EPO synthesis in kidneys (negative feedback).

Question 22

Explain the overview of erythrocytes physiology?

Answer 22

• They are concave (helps move around the capillaries/increased surface area/facillitates smooth flow)
• Contains Haemoglobin (transport gases)
• Remains in circulation for 120 Days (after that they are haemolysed in the spleen, releasing bilirubin.

Question 23

Explain the anatomy and physiology of the spleen?

Answer 23

Anatomy
* Located in the upper left quadrant of the abdomen, protected by rib 9-11.
* Blood supply comes from the splenic artery and the venous drainage occurs via the splenic vein.
**Physiology **
* F: filtration of blood cells
* I: immunological function (killing encapsulated organisms)/ Iron recycling
* S: Storage of erythrocytes and platelets
* H: Haematopoiesis ( during parts of gestation)

This is a mnemonic for some, but not all, encapsulated organisms:

Some:Streptococcus pneumoniae.

Killers:Klebsiella pneumoniae.

Have:Haemophilus influenzae type B (HiB).

Pretty:Pseudomonas aeruginosa.

Nice:Neisseriameningitidis.

Capsules:Cryptococcus neoformans (fungus).

Question 24

Describe the structure of haemoglobin and the types?

Answer 24

Haemoglobin is a tetramer, it has 4 globular protient subunit, each containing a heam group where O2 binds to.
Types of Hb
HbA: 2α and 2β, this comprises ~ 97% of Hb in the adult body.
HbA2: 2α and 2δ (delta), this comprises ~ 2% of Hb in the adult body.
HbF: 2α and 2γ (gamma), this comprises < 1% of Hb in the adult body.
HbS: Two normal alpha and two abnormal beta. This is seen in sickle cells.

Question 25

What is Anaemia?

Answer 25

Anaemia is defined as low blood concentration of Hb (erythrocytes)

Men: <130 g/L
Non-pregnant women: <120 g/L
Pregnant women: <110 g/L 1st trimester, <105 g/L 2nd & 3rd

Question 26

What do we get from a full blood count and describe the parameters?

Answer 26

HB: concentration of Hb (g/L or g/dL)
HCT: percentage of blood volume as RBCs (%)
MCV: average size of RBCs (fL)
MCH: Average Hb content in each RBC (pg)
MCHC: Average Hb concentration in RBCs (g/dL)
RDW: Range of deviation of RBC size
WBC: Number of white blood cells per unit of volume

Question 27

Anaemia Clinical sings and symptoms?

Answer 27

Non-specific symptoms:
Fatigue/lethargy
Dyspnoea
Palpitations
Feeling faint
Headache
Pallor
Tachycardia
Insomnia
Systolic flow murmur (severe cases)
Specific
Koilonychia (spoon shaped nails) : iron deficiency anaemia
Jaundice: haemolytic anaemia
Leg ulcers: sickle-cell anaemia, haemolytic anaemia
Bone deformities: thalassemia major

Question 28

What other useful tests can you do for Anaemia?

Answer 28

Reticulocyte count
Blood film
Bone Marrow Aspirate & Trephine
Haematinic levels: B12 & folate
Iron studies: ferritin, serum Fe, TIBC

Reticulocytes are immature blood cells

Size : big, small, normal
Shape : fragments, tear drop, spiculated, ovalocyte, spherocyte, eliptocyte
Colour: pale, normal, polychromasia
Inclusions: howell-jolly bodies, nuclear reminants, malarial parasites, basophilic stippling

Iron transported from enterocytes then enter into plasma or stored as ferritin

Once attached to transferrin it is transported and binds to transferrin receptors on RBC precursors

A state of iron deficiency will see reduced ferritin stores and then increased transferrin

Serum Fe
Hugely variable during the day

Ferritin
Primary storage protein & providing reserve, Water soluble

Transferrin Saturation
Ratio of serum iron and total iron binding capacity – revealing %age of transferrin binding sites that have been occupied by iron
Low = anaemia

TIBC (Total Iron Binding Capacity)
Measurement of the capacity of transferrin to bind iron
High = anaemia as lots wants to bind

Question 29

Cause of Anaemia 1

Answer 29

• Iron:
  Too little coming or too much going
  Malabsorbtion
  Bad diet
  Increased demand to normal
  Heavy bleeding (haemorrhage/menstruation)
  Parasites
• Overall lack of iron

Question 30

Cause of Anaemia 2

Answer 30

• 3 types:
  -Failure of production
  B12, Folate, Iron deficiency
  Epo deficiency in CKD
  Bone marrow failure: eg Aplastic Anaemia
  -Failure of appropriate utilisation
  Anaemia of chronic disease
  -Increased destruction
  Blood loss, haemolysis (AI, sickle, HS, TTP)
  Reticulocytosis

Question 31

Describe macro/micro and normacytic Anaemia?

Answer 31

Question 32

What is the Aetiology of Sickle cell disease?

Answer 32

Autosomal recessive condition, affecting the gene that codes for beta-globin.

Question 33

Describe the pathophysiology of sickle cell Anaemia?

Answer 33

Due to a point mutation, glutamate (hydrophilic) becomes valine (hydrophobic). This creates a hydrophobic region outside of the beta-globin.
So when a RBC is deoxygenated its protien conformation changes exposing a hydrophobic region which valine binds onto, creating the sickle cell shape.

Question 34

Clinical features of sickle cell disease?

Answer 34

Pain:
can be acute:
- vaso-occlusive crisis (incredibly painful);
- splenic sequestration crisis; and
- aplastic crisis.
chronic
neuropathic
Other features
-Haemolytic anaemia due to increased haemolysis. Sickel cell life is 30 days
-Other features include dactylitis (painful swelling in the hands and feet) and priapism (= prolonged erection without appropriate stimulation). There is also increased risk of stroke.

Question 35

What investigations would you do for sickle cell Anaemia 1?

Answer 35

**Bloods: **
↓ haemoglobin (anaemia).
↑ reticulocyte count (bone marrow compensating for ↑ haemolysis).
↑ LDH (an enzyme in RBCs) and ↑ bilirubin (from the breakdown of haem).

**Blood film: **
-Sickle cells.
-Polychromasia (reticulocytes are larger and stain a bluish colour).
-Target cells (= dark centre, surrounded by lighter ring).

LDH: Lactate dehydrogenase is an enzyme released from RBCs. You can find it in other locations in the body too.

Blood film = smearing a thin layer of blood on a microscope slide and then staining it so that you can see the cells.

Polychromasia = many colours = reticulocytes are present (they stain a bluish colour, in contrast to the pink RBCs).

Target cells = erythrocytes with a dark centre, surrounded by lighter ring (due to abnormal distribution of haemoglobin).

Howell-Jolly bodies:

These are nuclear remnants inside RBCs, which is not normal. On a blood film, the Howell-Jolly bodies are typically dark-purple-to-red in colour. Normally, these RBCs would be haemolysed by the spleen, but if the patient has a non-functioning spleen (e.g., due to damage caused by SCD), or their spleen has been removed, then the RBCs with Howell-Jolly bodies inside them will persist in the blood.

Question 36

What investigations would you do for sickle cell Anaemia 2?

Answer 36

Sickle solubility test:

Mix the patient’s blood with sodium dithionite.
If HbS is present, a precipitate forms → turbid solution.
This will be positive in patients who have SCT and patients who have SCD.

Electrophoresis:

Blood sample is treated to release Hb.
Sample is placed in gel and subjected to an electric charge.
Sample moves through the medium, forming characteristic patterns.

HPLC:

High-performance liquid chromatography.
Blood sample is treated to release Hb.
Sample is injected into HPLC at high pressure.
Different types of Hb move through at different speeds.
This enables the HPLC to measure percentage of Hb variants.
Therefore, the machine can produce a graph.

Question 37

What is the long term management of sickel cell anaemia?

Answer 37

Conservative:
↑ fluid intake and trigger avoidance (e.g., strenuous exercise).

Medical:
Folate supplementation, immunisations, and antibiotic prophylaxis.

Prevention of Vaso-Occlusive Crises (VOCs):
Top-up blood transfusions and hydroxycarbamide (aka hydroxyurea, which increases HbF, thereby diluting HbS and reducing the risk of sickling).

Management of Chronic Complications:
Blood transfusions risk iron overload → chelation therapy.
Monitor for organ damage: ECG, BP, retinal screening, and urinalysis to check for protein (kidney damage).

Folate supplementation: Folate plays a role in erythropoiesis.

Antibiotic prophylaxis: Taking abx regularly to prevent infections.

Hydroxycarbamide = hydroxyurea = drug that increases HbF (this dilutes the concentration of HbS and reduces the risk of sickling).

Chelation therapy = Kel-AY-shun therapy = drugs that bind a potentially harmful substance and allow it to be excreted safely.

BP = Blood pressure.

Organ damage:

Sickle cell disease can damage many parts of the body, such as the heart, eyes, and kidneys – you need to monitor this. I won’t provide an in-depth explanation of why you do ECGs, BP measurements, retinal screening, or urinalysis. This will become more obvious as the year progresses and you learn more about the human body.

Question 38

What is the emergency management of sickle cell anaemia?

Answer 38

Pain relief within 30 mins and reassess every 30 mins.
-O2.
-IV fluids.
-Antibiotics (if they have an infection).
-Blood transfusion.

Question 39

What is thalassaemia?

Answer 39

Thalassaemia is the disorder of globulin chain synthesis, it is inherited.
There is either underproduction or absence of Beta or alpha globulin chain.
-4 Alpha gene: 2 on each chr 16
-2 Beta gene: 1 on each chr 11

Alpha thalassaemia: is usually due to large deletion in alpha globin complex
Beta thalassaemia: usually due to point mutation in he beta gene

Question 40

Types of Alpha thalassaemia?

Answer 40

One gene deleted
* Clinical state is normal - silent carrier
* Occasional low RBC indices

Two genes deleted (microcytic anaemia)
* Thalassaemia trait – mild anaemia and low RBC indices

3 α genes deleted
* HbH disease: (ß4) tetramers form
* Anaemia, low MCV, MCH
* Haemolysis features: Body doesn’t like the weird beta only haemoglobin.
Hepatosplenomegaly, leg ulcers, jaundice

Deletion of all four α genes
* Barts Hydrops Fetalis: Death in utero or at term
* Hb Barts: γ4 self assembles – cannot transport O2
* No α chain production

Question 41

Types of Beta thalassaemia?

Answer 41

β0: absent globin production
β+: reduced production

abnormality in 1 inherited gene: b-thal trait
Microcytic anaemia, high HbA2

Abnormality in both genes:
b-thal intermedia or b-thal major (BTM)
Transfusion requirements and varying severity

Question 42

What are the investigations for beta thalassaemia major?

Answer 42

Anaemia investigations PLUS
-Hb electrophoresis.: HbA1 absent, HbA2 raised, increased (80-100%)
-Radiography: Medullary expansion – marrow hypertrophy – hair on end appearance on X ray skull