GEP (Foundation Module) Week 3 Flashcards
Identify the anatomy of the heart?
What does the Right Brachiocephalic trunk bifurcate into?
The brachiocephalic trunk bifurcates into the right subclavein artery and the right common carotid artery.
what does the Common carotid artery bifurcate into?
- It splits into an external carotid artery (Supplies neck and outside of cranium).
- internal carotid artery (supplies the inside of cranium).
What does the subclavian artery become after passing what anatomical border?
The subclavian artery becomes the axillary artery after passing the lateral border of the first rib.
What does the axillary artery give rise to at what anatomical border?
The axillary artery gives rise to the brachial artery at the inferior border of teres major muscle.
What does the brachial artery bifurcate into?
The brachial artery bifurcates into the radial and ulnar artery
What does the thoracic aorta become as it travels down and what does it bifurcate into?
The thoracic aorta becomes the abdominal aorta and birfurcates into the right and left common iliac artery.
What doe the common iliac artery bifurcate into?
It birfucates into Internal and external iliac artery.
What does the external iliac artery become and at what anatomical border?
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.
What does the femoral artery become?
At the distal part of the thigh, the femoral artery becomes the popliteal artery which runs behind the knee and passes the adductur hiatus
What does the popliteal artery give rise to?
The popliteal artery gives rise to the anterior and posterior tibial artery.
What is DNA
Deoxyribonucleic acid and are made up of nucleotides. Each nucleotides containing a phosphate group, a sugar group and a nitrogenous base.
What are the nitrogenous bases of DNA?
- Purine group: A (Adenine), G (Guanine)
- Pyrimidines: C (Cytosine), T (Thymine)
What is a codon?
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.
How does protien synthesis occur?
- RNA polymerase unzips DNA in nucleus
Get the editing, splicing, capping (all transcription) - mRNA leaves nucleus
3.Translation ribosome comes along to make protein w/ tRNA codons.
4.Protein starts to fold after it has finished forming
What are the types of protien structures?
- Primary structure
- secondary structure (beta pleated sheets/alpha helix)
- tertiary structure
- quaternary structure
What are the different types of mutations that can happen in codons?
Frameshift insertion/deletion
Conservative, functioning
Non-conservative, non-functioning
Functions of Blood?
transport (e.g., oxygen, hormones, and glucose),
immunity (e.g., leukocytes),
haemostasis (= stopping blood loss), and
thermoregulation (blood carries heat).
What is the composition of Blood?
How are Red blood cells formed (Erythrocyte) also know as Erythropoiesis?
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.
Describe the regulation of Erythropoiesis?
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).
Explain the overview of erythrocytes physiology?
- 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.
Explain the anatomy and physiology of the spleen?
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).
Describe the structure of haemoglobin and the types?
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.
What is Anaemia?
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
What do we get from a full blood count and describe the parameters?
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
Anaemia Clinical sings and symptoms?
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
What other useful tests can you do for Anaemia?
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
Cause of Anaemia 1
- Iron:
Too little coming or too much going
Malabsorbtion
Bad diet
Increased demand to normal
Heavy bleeding (haemorrhage/menstruation)
Parasites - Overall lack of iron
Cause of Anaemia 2
- 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
Describe macro/micro and normacytic Anaemia?
What is the Aetiology of Sickle cell disease?
Autosomal recessive condition, affecting the gene that codes for beta-globin.
Describe the pathophysiology of sickle cell Anaemia?
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.
Clinical features of sickle cell disease?
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.
What investigations would you do for sickle cell Anaemia 1?
**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.
What investigations would you do for sickle cell Anaemia 2?
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.
What is the long term management of sickel cell anaemia?
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.
What is the emergency management of sickle cell anaemia?
Pain relief within 30 mins and reassess every 30 mins.
-O2.
-IV fluids.
-Antibiotics (if they have an infection).
-Blood transfusion.
What is thalassaemia?
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
Types of Alpha thalassaemia?
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
Types of Beta thalassaemia?
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
What are the investigations for beta thalassaemia major?
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
