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NEJM Jan2014-Sep2015 > Oct 2014 > Flashcards

Oct 2014 Flashcards

1
Q

In patient with severe COPD on inhaled tiotropium, salmeterol and fluticasone, what is the effect of discontinuing fluticasone on the following:

  1. Time to first mode/severe COPD exacerbation
  2. FEV1
A
  1. No difference compared to patients that remain on fluticasone.
  2. Decreased FEV1 (i.e. decrease in lung function)
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2
Q

What genetic abnormality predisposes a person coeliac disease? How common is this association

A

HLA-DQ2 (DQA10501-DQB10201) if found in 90% of coeliac patients.

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3
Q

Coeliac disease has a genetic predisposition:

  1. What is the prevalence of coeliac disease?
  2. What is the prevalence in 1st-degree relative of a patient with known coeliac disease?
A
  1. 1%

2. 15%

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4
Q

What are the 4 mechanisms of microcytic anaemia?

A
  1. Fe-deifiency = iron/heme problem
  2. Anaemia of inflammation = iron/heme problem
  3. Sideroblastic anaemia = protopotphyrin/heme problem
  4. Thalassaemia = globin problem
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5
Q

What is thalassaemia?

A

Disease of Hb synthesis

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6
Q

What are the 4 types of alpha-thalassaemia?

A
  • Trait 1 and Trait 2 - both with mild anaemia/microcytosis (worse in Trait 2)
  • Haemoglobin H disease (tetramer of beta-chains) - deletion or mutation of 3 alpha-chain genes causing a marked anaemia often with a haemolytic component

Haemoglobin Barts - lack of alpha-chain production resulting in hydrops fetalis

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7
Q

What is the difference between ‘trans’ and ‘cis’ forms of thalassaemia?

A

trans = one copy of the gene is mutated on each chromosome

cis = one chromosome has both genes mutated

cis is worse and leads to Haemoglobin H or Haemoglobin Barts disease.

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8
Q

What is beta-thalassaemia?

A

Due to only one Hb beta-chain on chromosome 11, 2 types:

  1. Thalassamia minor (heterozygous)
  2. Thalassaemia major (homozygous)
  3. Thalassaemia intermedia (homozygous, but with residual beta-chain synthesis)
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9
Q

What ethnicity is beta-thalassaemia most common in?

A

Mediterranean and South-East asia.

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10
Q

What is the difference in clinical manifestations of beta-thalassaemia minor and major?

A 
minor = mild microcytic anaemia
major = manifests soon after birth as transfusion dependent anaemia
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11
Q

What is Haemaglobin E disease?

A

Lysine is subtituted for glutamine at position 26 of the beta-chain.

Mutation also activates an alternative mRNA site leading to reduced protein synthesis.

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12
Q

Compare the clinical manifestations of homozygous and heterozygous Haemaglobin E.

A

Heterozygous = microcytosis with target cells

Homozygous = only mild anaemia

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13
Q

Describe the 3 mechanisms of anaemia in Anaemia of Inflammation.

A
  1. Inflammatory cytokine suppresses EPO production
  2. Elevated hepcidin (acute phase reactant) leads to decreased iron absorption and reduced iron release from stores.

The result is a microcytic anaemia.

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14
Q

Describe the mechanism of decreased iron absorption in the presence of hepcidin.

A
  1. Ferroportin mediates cellular efflux of iron:
    • Enterocytes: efflux of absorbed iron into blood (absorption)
    • Hepatocytes and macrophages: efflux of intracellular iron into the blood (stores)
  2. Hepcidin leads to down-regulation of surface ferroprotin on these cells therefore leading to:
    • Reduced iron absorption by enterocytes.
    • Reduced iron release from body stores.
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15
Q

What are the 2 reasons women are more prone to iron deficiency anaemia than men?

A
  1. Menses (blood loss)

2. Pregnancy (increased demand)

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16
Q

What are the 2 mechanisms that an athlete might get anaemia?

A
  1. Exercise-induced haemolysis leading to urinary loss

2. Training induced inflammation leads to elevated hepcidin and hence anaemia of inflammation (Fe-deficiency anaemia)

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17
Q

True/False: Obese people often have elevated levels of hepcidin that causes Fe-defiency anaemia.

A

True.

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18
Q

Which of the following is the main site of iron absorption in the GIT:

  1. stomach
  2. duodenum
  3. jejunum
  4. colon
A

Duodenum

NB: bariatric surgery that leads to bypass this part of the bowel leads to Fe-deficiency anaemia.

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19
Q

True/False: in anaemia of inflammation, the MCV is often less than 70 fl.

A

False - rare.

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20
Q

Target cells are found in a microcytic blood film, what 2 conditions do you suspect?

A
  1. Beta-thalassaemia

2. Haemoglobin E disease

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21
Q

Compare the formal diagnostic process of alpha and beta thalassaemia.

A

Beta-thalassaemia:

  • MCV 65-75 fl
  • Hb EPG reveals increased Hb A2 fraction

Alpha-thalassaemia:

  1. Traits:
    - Diagnosis of exclusion in patient with microcytosis and mild or no anaemia with normal iron levels.
    - Hb EPG not useful - disease is silent.
    - DNA analysis required for diagnosis
  2. Haemaglobin H:
    - Severe microcytosis +/- haemolysis +/- splenomegaly
    - Hb EPG with Hb H (tetramer of beta-chains)
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22
Q

What is the Hb A2 fraction?

A

Increased production of the Hb that contains the delta-chain (Hb A2)

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23
Q

True/False: Hb EPG is required in the diagnosis of alpha-thalassaemia trait.

24
Q

Comment about the following parameters in the diagnosis of anaemia of inflammation:

  1. EPO levels
  2. Renal function
  3. Fe-stores
A

Anaemia of inflammation is a diagnosis of exclusion.

  1. EPO - normal (not raised despite anaemia)
  2. Renal function - normal
  3. Fe-stores - normal
25
What happens to the total iron binding capacity (TIBC) in Fe-deficiency? What are the 3 confounders of this?
TIBC (i.e. transferrin saturation) is elevated in Fe-deficiency - specific. Not 'sensitive' as the following may lower the TIBC: 1. inflammation 2. aging 3. poor nutrition
26
How is soluble transferrin receptor (sTR) useful in the diagnosis of Fe-deficiency? What other conditions may confound interpretation of the sTR?
- sTR is elevated in Fe-deficiency. - Unlike TIBC, sTR is NOT affected by inflammation. - Conditions that increase red cell mass also increase the sTR i.e. haemolytic anaemia and CLL.
27
Aside from blood loss (i.e. menses and bleeding) what are the 'natural' mechanisms of removing iron from the body?
None. Assessment of the GIT for occult bleed is therefore mandatory for patients with a diagnosis iron-deficiency without a clear cause.
28
What are the treatment options for thalassaemia?
1. Chronic transfusions and iron chelation | 2. Stem-cell transplantation - if available, best treatment option
29
A patient with thalassaemia trait wishes to have children, what should test should the partner undergo?
FBC for MCV - if MCV is less than 75 then formal genetic testing is required.
30
What is the treatment of anaemia of inflammation?
Support and treat the cause of inflammation.
31
Which type of dietary iron is better absorbed; heme or non-heme?
Rate of absorption is 10x better from 'heme' sources.
32
Give examples of heme and non-heme dietary iron sources.
``` Heme = meat, seafood and poultry Non-heme = plants and iron-fortified foods ```
33
What is the effect of tea and coffee upon the absorption of iron?
Reduces absorption by 90%. Avoid when taking iron supplements.
34
What vitamin should be taken with Fe-tablets to improve iron absorption?
Vitamin C.
35
What happens to the reticulocyte count and Hb level during iron therapy?
- Reticulocytes increase in 1 week. | - Hb increases by 2nd week.
36
What is the difference in mortality at 90 days in anaemic patients with septic shock in ICU that are: 1. Transfused when Hb less than 90 2. Transfused when Hb less than 70
No difference - therefore no need to transfuse uness Hb less than 70. Irrespective of chronic CVD, older age or disease severity.
37
In patient with T2DM what is the effect of intensive vs. standard standard glucose control to the following end-points: 1. All-cause mortality 2. ESRF 3. Retinopathy
1. No benefit in all-cause mortality 2. Benefit with ESRF 3. No benefit in retinopathy
38
What is the Henderson-Hasselbach equation?
pH = pK + log10( [HCO3-] / [0.03 x PaCO2] )
39
What range of acid pH is compatible with life?
pH 6.8 - 7.8 (H+ = 16-160 nmol/L)
40
In regards to acid-base homeostasis, over what period of time do the following compensations occur for acidosis: 1. Respiratory compensation 2. Metabolic compensation
1. Fast - hours (respiratory rate) | 2. Slow - 2-5 days (HCO3- levels)
41
How is anion gap calculated? What is the normal range?
AG = [Na+] + [K+] - [Cl-] - [HCO3-] Normal range = 8 - 16 NB: sometime [K+] is not included.
42
Describe the following: 1. Anion 2. Cation
1. Anion = atoms that have gained electrons e.g. Cl-, HCO3- | 2. Cation = atoms that have lost electrons e.g. Na+, K+
43
What are the causes of high anion gap metabolic acidosis (GOLDMARK)? Which is the most common cause?
GOLDMARK (from Lancet) G — glycols (ethylene glycol & propylene glycol) O — oxoproline, a metabolite of paracetamol L — L-lactate (anaerobic metabolism) D — D-lactate (from bacterial digestion of carbohydrates) M — methanol A — aspirin R — renal failure, rhabdomyloysis K — ketoacidosis, ketones generated from starvation, alcohol, and diabetic ketoacidosis Most common = lactic acidosis (50%) - often due to shock or tissue hypoxia
44
Give examples for the following mechanism of high anion gap metabolic acidosis: 1. overproduction of acid 2. underexcretion of acid 3. cell lysis
1. overproduction = ketoacidosis, lactic acidosis, alcohol, drugs 2. underexcretion of acid = ESRF 3. cell lysis = rhabdomyolysis
45
What is the effect of hypoalbuminaemia upon anion gap (AG)?
1g/L drop in albumin leads to an AG increase of 2.5
46
Patient with short gut syndrome may cause have a high anion gap despite a normal serum lactate, how is this possible?
Short gut syndrome causes a D-lactate acidosis (lactate produced by colonic bacterial metabolism of undigested carbohydrates), rather than L-lactate acidosis. L-lactate is the lactate normally measure in the serum.
47
What are the causes of normal anion gap metabolic acidosis (HARD ASS)?
``` H = hyperalimentation A = Addisons disease R = Renal Tubular Acidosis - distal (renal loss of HCO3-) D = Diarrhoea (GI loss of HCO3-) ``` ``` A = Acetazolamide S = Spiranolactone S = Saline Infusion. ```
48
Elevation in which electroyte is often associated with normal anion gap metabolic acidosis? What is the mechanism for acidosis?
Chloride - hence the term 'hyperchloremic metabolic acidosis' Rise in Cl- leads to drop in HCO3- and therefore acidosis.
49
In normal anion gap metabolic acidosis (NAGMA), what is the urinary anion gap?
Calculated urinary AG = [Na+] + [K+] - [Cl-] Usually negative in NAGMA
50
What are the 2 most common causes of metabolic alkalosis?
1. Loss of gastric fluid (i.e. vomiting) | 2. Diuretic use
51
Given the PaO2 and PaCO2, how does one estimate the A-a gradient? Given a persons age what is a rough estimation of the expected A-a gradient in a healthy adult.
A-a gradient = 150 - 1.25(PaCO2) - PaO2 A-a gradient = (Age/4) + 4 NB: Normal adult range = 5-20 mmHg (i.e. 4-64 yrs)
52
Patient has metabolic acidosis (low HCO3-), what is the approach to determining the diagnosis?
1. Consider respiratory compensation: - expected PaCO2 = 1.5[HCO3-] + 8 +/- 2 mmHg - low = respiratory alkalosis - high = additional respiratory acidosis 2. Calculate AG: high vs. normal - HIgh = MUDPILES (calculate delta-delta or osmolality gap) - Normal = HARD ASS (calculate urinary anion gap)
53
For normal anion gap metabolic acidosis, what is the significance of a positive vs. negative urinary anion gap (AG)? Given than the urinary AG is positive, how does one differentiate between possible diagnoses?
Negative urinary AG = diarrhoea, salin infusion, proximal RTA (type 1) Positive urinary AG = distal RTAs: - type 1 RTA = serum [K+] low and urinary pH > 5.5 - type 4 RTA = serum [K+] high and urinary pH > 5..5 in hyperaldosteronism
54
Patient presents with respiratory acidosis (PaCO2 great than 42 mm Hg), what is the approach in determining the diagnosis?
1. Consider metabolic compensation via change in HCO3: - 1 mmol/L increase per 10mmHg PaCO2 = respiratory acidosis. - less than 1 mmol/L increase per 10mmHg PaCO2 = metabolic acidosis. - 4-5 increase per 10mmHg PaCO2 = 'chronic' respiratory acidosis. - great than 5 increase per 10mmHg PaCO2 = additional metabolic alkalosis. 2. Consider the A-a gradient estimation (150 - 1.25(PaCO2) - PaO2): - less than 10-20 = hypoventilation without intrinsic lung disease - greater than 10-20 = hypoventilation with intrinsic lung disease +/or V-Q mismatch
55
Patient presents with metabolic alkalosis ( [HCO3-] great than 26 mmol/L), what is the approach in determining the diagnosis?
1. Consider respiratory compensation: - expected PaCO2 = 0.7 ( [HCO3-] - 24 ) + 40 +/- 2 mmHg - low = additional respiratory alkalosis - high = additional respiratory acidosis 2. Consider presence of exogenous alkali or severe hypercalcaemia: - YES = milk alkali syndrome (hypercalcaemia in renal failure) - NO = consider response to Cl- (give NaCl or KCl) - Cl- responsive = gastric fluid loss or diuretic use leading to Cl- loss - Cl- resistant (i.e. urinary Cl- > 40mmol/L): - Urinary K+ less than 20mmol/day = laxative abuse - Urinary K+ more than 30mmol/day: - Low/normal BP = Bartter/Gitelman syndrome - High BP = Mineralcorticoid excess
56
What do Bartter and Gitelman syndromes cause and how are they differentiated?
Both cause: metabolic alkalosis high urinary Cl- and urinary K+ low/normal BP Difference: Bartter = high urinary Ca++ Gitelman = low urinary Ca++
57
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NEJM Jan2014-Sep2015 (4 decks)

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