Extra Stuff/Last Minute

Question 1

You should avoid grapefruit if you are taking which drug?

Answer 1

Atorvastatin

Question 2

What are the symptoms of HDN? (5-6)

Answer 2

• jaundice due to bilirubin build up in the body - the liver cannot filter the excesive amounts from RBC breakdown
• biliruibin may casue kernicterus in the brain - neurological damage
• worse cases cause anaemia
• the liver and spleen increase RBC production and become enlarged (these are the sites of heamatopoesis in babies)
• liver dysfunction
• severe complication - hydrops fetalis - swelling of tissues, usually fatal

Question 3

what is the Coombs test, roughly how does it work?

Answer 3

the coombs test identifies maternal anti-D antibodies.

• In the direct coombs test, foetal blood is tested for the presence of antibodies already having an effect.
• In the indirect test, the mothers blood is tested to find anti D that might casue a problem in the future.
• The test uses antibodies that bind to Anti-D antibodies (which are already bound to RBCs) and cause agglutination

Question 4

In statistics, what is an outlier? What can an outlier be caused by (4) and which of these types of outliers should be included in a statistical analysis?

Answer 4

Unexpected results, which may reflect:

• idiosyncrasies in the subject (for example unusual metabolism),
• errors in measurement (faulty equipment),
• errors in interpretation (misreading a meter reading), or
• errors in calculation (misplaced decimal points).

Only the first of these is a “real” result which deserves to be included in the analysis.

Question 5

In statistics, what is skew? What is positive skew and negative skew?

Answer 5

Normally distributed info has no skew. However, when you measure real life variables, they do not always have a symmetrical distribution around the mean like a normal distribution does.

• Positive skew means the ‘tail’ on the RIGHT of the (ab)normal graph is longer than the tail on the left (SEE PICTURE)
• Negative skew has a longer tail on the left.

Question 6

• Which test might you use to work out whether a distribution is normally distributed or not?
• How do you carry out this test?
• How do you interpret the result of the test? What can it show you, and what can it not show you?

Answer 6

• Shapiro-Wilk test
• Carry out with a computer programme
• Get result coefficient W: if if the distribution is close to normal, this figure will be close to 1
• Get probability p: if p is less than 0.05, the distribution is very unlikely to be normal.
• Shapiro-Wilk will indicate if the data has a non-normal distribution. It can’t definitely say that the data is normally distributed though.

Question 7

A number of statistical tests can’t be done if the data are not normally distributed (basically because many tests assume normality of the data). But when data are not normally distributed they can sometimes be transformed to become normal. How might this be acheived?

Answer 7

take the log values of the data - variables that are skewed to the right are often transformed by taking the log values.

Question 8

to do a t test initially what must you assume about the data?

Answer 8

that the data is normally distributed

Question 9

What do you use the one-sample t test for?

Answer 9

The one sample t-test can be used to determine if a sample mean is representative of the population mean. This can validate that the sample represents the population, or it can be used to determine whether the sample shows differences from the population in the characteristic being measured – for example, you might want to know whether junior doctors had higher blood pressure than the rest of the population of the same age.

Question 10

what do you use the unpaired t test for?

Answer 10

The unpaired two-sample t-test is used to determine the difference between two independent groups - for example, if you were comparing the forced expiratory volume of asthmatics versus non-asthmatics.

Question 11

What do you use the paired t test for?

Answer 11

The paired t-test is used to compare dependent samples or groups (for example comparing a subject at two time points, such as before and after treatment).

Question 12

What two values can give you an understanding of whether two sets of variables have correlation with one another?

Answer 12

Pearson’s correlation coefficient r (or just Pearson’s r) is the usual statistic that describes the linear correlation between two variables.

• Pearson’s r takes a value between -1 and 1, with -1 indicating perfect negative correlation and 1 indicating perfect positive correlation. 0 means there is no correlation.
• When calculating a correlation, statistical packages like StatsDirect and SPSS will give you the value for the correlation (r) along with a p value. If the p value is <0.05 this would be telling us that there is a significant correlation.

Question 13

What do you use to predict the value of one variable from the value of another variable?

Answer 13

Linear regression.

Question 14

what are the three types of embryonic haemoglobin? (less than 2 months old)

Answer 14

• Gower 1 (zeta2, epsilon2 or z2e2)
• Gower 2 (alpha2, epsilon2 a2e2)
• Portland (zeta2, gamma2 z2g2)

z and e are unique to embryonic haemoglobin

Question 15

in the second month of development, which type of haemoglobin becomes predominant?

Answer 15

foetal haemoglobin (alpha2, gamma2 a2g2)

Question 16

At birth, what is the composition of haemoglobin?

Answer 16

• 50-95% foetal haemoglobin (a2g2)
• the rest adult haemoglobin A (a2b2)
• and a little adult haemoglobin A2 (a2d2) which is synthesised in the third trimester and continues to adulthood at about 2.5%

Question 17

what compounds other than oxygen can haemoglobin transport?

Answer 17

• carbon dioxide
• nitric oxide - this is carried bound to a globin protein thiol group, and is released at the same time as oxygen.

Question 18

where is haemoglobin produced?

Answer 18

• the heme part: mitochondria of immature RBCs
• the globin part: ribosomes of immature RBCs

Question 19

Decribe the cooperatvie oxygen binding to haemoglobin

Answer 19

haemoglobin can bind up to 4 oxygen. As each oxygen is added, there is a confirmationcal change to the shape of the binding sites for the other 4 oxygen, which gives each site more affinity for oxygen: the more oxygen a Hb has, the easier it is to pick up more.

Question 20

What is haemoglobins oxygen binding capacity decreased by?

Answer 20

• the presence of carbon monoxide becuase this binds to the same site as oxygen, with much greater affinity. (carboxyhaemoglobin - cherry red)
• other compounds bind to the same site as oxygen: cyanide CN-, Sulfur monoxide SO, Nitric oxide NO, Sulfide S2-, Hydrogen Sulfide H2S
• the presence of Carbon Dioxide and protons (acid), which together? bind to a different site on the Hb and lower affinity for Oxygen (the Bohr effect). Shifts the Hb oxygen dissociation curve to the right

Question 21

When might iron overload take place? How does iron do damage to cells?

Answer 21

• Iron overload sometimes occurs in disorders in which normal regulation of iron absorption is impaired. It is most commonly produced iatrogenically through the parenteral administration of large amounts of iron or blood for therapeutic purposes.
• Iron can be toxic. Its ability to donate and accept electrons means that if iron is free within the cell, it can catalyze the conversion of hydrogen peroxide into free radicals and ultimately kill the cell.

Question 22

Which chemical processes are iron used for in the body? (3) Which molecules are iron bound into to carry out these processes? (2)

Answer 22

• heme: redox reactions and electron transport processes. These reactions and processes are required for oxidative phosphorylation, the principal source of energy for human cells.
• iron-sulfur proteins: oxidative phosphorylation.

Question 23

Which molecules containing iron are used for the storage and transport of oxygen? (2)

Answer 23

• Haemoglobin: transport oxygen from the lungs to the tissues and to transport carbon dioxide back to the lungs.
• myoglobin: storage and diffusion of oxygen in muscle cells.

Question 24

How does the body prevent iron overload?

Answer 24

humans have no physiologic regulatory mechanism for excreting iron. Most humans prevent iron overload solely by regulating iron absorption. Those who cannot regulate absorption well enough get disorders of iron overload. In these diseases, the toxicity of iron starts overwhelming the body’s ability to bind and store it.

Question 25

Where and how is iron stored in the body?

Answer 25

ferritin complexes that are present in all cells, but most common in bone marrow, liver, and spleen. The liver’s stores of ferritin are the primary physiologic source of reserve iron in the body.

Question 26

How much iron do we have in our bodies if we are healthy?

Answer 26

4 to 5 grams of iron in their bodies. Of this, about 2.5 g is contained in the hemoglobin needed to carry oxygen through the blood,

Question 27

Which iron ion is toxic?

Answer 27

Because of its toxicity, free soluble iron (soluble ferrous ions Fe(II)) is kept in low concentration in the body.

Question 28

How does iron depletion cause damage?

Answer 28

Oxygen transport is so important to human life that severe anemia harms or kills people by depriving their organs of enough oxygen. Iron-deficient people will suffer or die from organ damage well before cells run out of the iron needed for intracellular processes like electron transport.

Question 29

which iron compound might you find in people with iron overload?

Answer 29

Iron is also stored as a pigment called hemosiderin in an apparently pathologic process. This molecule appears to be mainly the result of cell damage. It is often found engulfed by macrophages that are scavenging regions of damage. It can also be found among people with iron overload due to frequent blood cell destruction and transfusions

Question 30

How do people lose iron, (4) and how much per day?

Answer 30

• people lose a small but steady amount by:
• sweating
• shedding cells of the skin and the mucosal lining of the gastrointestinal tract.
• Menstruation

The total amount of loss for healthy people in the developed world amounts to an estimated average of 1 mg a day for men, and 1.5–2 mg a day for women with regular menstrual periods. People with gastrointestinal parasitic infections, more commonly found in developing countries, often lose more.

Question 31

Describe the detail of iron absorption at the intestinal lining, including the enzyme and receptor involved. How is the iron then moved into the blood?

Answer 31

• dietary iron can be absorbed as part of a heme protein or must be in its ferrous Fe2+ form. A ferric reductase enzyme on the epithelial cells, Dcytb, reduces ferric Fe3+ to Fe2+. A protein called divalent metal transporter 1 DMT1, which transports all kinds of divalent metals into the body, then transports the iron across the enterocyte’s cell membrane and into the cell.
• These intestinal lining cells can then either store the iron as ferritin, which is accomplished by Fe3+ binding to apoferritin or the cell can move it into the body, using a protein called ferroportin. The body regulates iron levels by regulating each of these steps. For instance, cells produce more Dcytb, DMT1 and ferroportin in response to iron deficiency anemia

Question 32

Explain the mechanism of anaemia of chronic disease

Answer 32

• Interleukin-6 appears to be the central mediator of anaemia of chronic disease in a range of inflammatory diseases, including end-stage renal disease and rheumatoid arthritis.
• It induces the expression of hepcidin, which suppresses the expression of the iron transporter, ferroportin-1, so inhibiting the absorption of iron from the duodenum and the release of iron from the reticuloendothelial system

Question 33

Deficiency of which vitamins can lead to anaemia?

Answer 33

Folic acid and vit b12

Question 34

What is thelassaemia? What are the different severities and why do they occur?

Answer 34

Genetic disorder in which the globin chains of haemoglobin do not function properly. Can affect the alpha or beta chain. 4 genes are responsible for producing alpha chain: if one gene is affected there are few symptoms, if two are affected this is alpha thelassaemia trait, three genes gives you haemoglobin H disease which requires lifelong blood transfusions for anaemia, 4 genes is alpha thelassaemia major and a child is unlikely to survive pregnancy.

Question 35

What is sideroblastic anaemia?

Answer 35

Sideroblastic anemia is a disease in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells. It may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome. In sideroblastic anemia, the body has iron available but cannot incorporate it intohemoglobin, which red blood cells need to transport oxygen efficiently

Question 36

What is pernicious anaemia?

Answer 36

A condition in which insufficient vitamin b12 is absorbed from the GI tract. This leads to macrocyclic anaemia, as DNA cannot form fast enough without b12, so the cell divides later then it should and forms bigger RBCs.

Question 37

Describe 5 disorders of consciousness

Answer 37

• Locked-in syndrome: The patient has awareness, sleep-wake cycles, and meaningful behavior (viz., eye-movement), but is isolated due to quadriplegia and pseudobulbar palsy.
• Minimally conscious state: The patient has intermittent periods of awareness and wakefulness and displays some meaningful behavior.
• Persistent vegetative state: The patient has sleep-wake cycles, but lacks awareness and only displays reflexive and non-purposeful behavior.
• Chronic coma: The patient lacks awareness and sleep-wake cycles and only displays reflexive behavior.
• Brain death: The patient lacks awareness, sleep-wake cycles, and behavior

Question 38

What is the simple procedure for assessing whether the patient is conscious?

Answer 38

The simple procedure begins by asking whether the patient is able to move and react to physical stimuli. If so, the next question is whether the patient can respond in a meaningful way to questions and commands. If so, the patient is asked for name, current location, and current day and time. A patient who can answer all of these questions is said to be “oriented times three” (sometimes denoted “Ox3” on a medical chart), and is usually considered fully conscious.

Question 39

Go through the Glasgow Coma Scale

Answer 39

Best eye response (E)

There are 4 grades starting with the most severe:

1. No eye opening
2. Eye opening in response to pain. (Patient responds to pressure on the patient’s fingernail bed; if this does not elicit a response, supraorbital and sternal pressure or rub may be used.)
3. Eye opening to speech. (Not to be confused with an awaking of a sleeping person; such patients receive a score of 4, not 3.)
4. Eyes opening spontaneously

Best verbal response (V)

There are 5 grades starting with the most severe:

• T Patient is intubated

1. No verbal response
2. Incomprehensible sounds. (Moaning but no words.)
3. Inappropriate words. (Random or exclamatory articulated speech, but no conversational exchange)
4. Confused. (The patient responds to questions coherently but there is some disorientation and confusion.)
5. Oriented. (Patient responds coherently and appropriately to questions such as the patient’s name and age, where they are and why, the year, month, etc.)

Best motor response (M)

There are 6 grades starting with the most severe:

1. No motor response
2. Extension to pain (abduction of arm, external rotation of shoulder, supination of forearm, extension of wrist, decerebrate response)
3. Abnormal flexion to pain (adduction of arm, internal rotation of shoulder, pronation of forearm, flexion of wrist, decorticate response)
4. Flexion/Withdrawal to pain (flexion of elbow, supination of forearm, flexion of wrist when supra-orbital pressure applied ; pulls part of body away when nailbed pinched)
5. Localizes to pain. (Purposeful movements towards painful stimuli; e.g., hand crosses mid-line and gets above clavicle when supra-orbital pressure applied.)
6. Obeys commands. (The patient does simple things as asked.)