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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.

A

False.

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
Q

What happens to the total iron binding capacity (TIBC) in Fe-deficiency?

What are the 3 confounders of this?

A

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
Q

How is soluble transferrin receptor (sTR) useful in the diagnosis of Fe-deficiency?

What other conditions may confound interpretation of the sTR?

A
  • 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
Q

Aside from blood loss (i.e. menses and bleeding) what are the ‘natural’ mechanisms of removing iron from the body?

A

None.

Assessment of the GIT for occult bleed is therefore mandatory for patients with a diagnosis iron-deficiency without a clear cause.

28
Q

What are the treatment options for thalassaemia?

A
  1. Chronic transfusions and iron chelation

2. Stem-cell transplantation - if available, best treatment option

29
Q

A patient with thalassaemia trait wishes to have children, what should test should the partner undergo?

A

FBC for MCV - if MCV is less than 75 then formal genetic testing is required.

30
Q

What is the treatment of anaemia of inflammation?

A

Support and treat the cause of inflammation.

31
Q

Which type of dietary iron is better absorbed; heme or non-heme?

A

Rate of absorption is 10x better from ‘heme’ sources.

32
Q

Give examples of heme and non-heme dietary iron sources.

A 
Heme = meat, seafood and poultry
Non-heme = plants and iron-fortified foods
33
Q

What is the effect of tea and coffee upon the absorption of iron?

A

Reduces absorption by 90%.

Avoid when taking iron supplements.

34
Q

What vitamin should be taken with Fe-tablets to improve iron absorption?

A

Vitamin C.

35
Q

What happens to the reticulocyte count and Hb level during iron therapy?

A
  • Reticulocytes increase in 1 week.

- Hb increases by 2nd week.

36
Q

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
A

No difference - therefore no need to transfuse uness Hb less than 70.

Irrespective of chronic CVD, older age or disease severity.

37
Q

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
A
  1. No benefit in all-cause mortality
  2. Benefit with ESRF
  3. No benefit in retinopathy
38
Q

What is the Henderson-Hasselbach equation?

A

pH = pK + log10( [HCO3-] / [0.03 x PaCO2] )

39
Q

What range of acid pH is compatible with life?

A

pH 6.8 - 7.8 (H+ = 16-160 nmol/L)

40
Q

In regards to acid-base homeostasis, over what period of time do the following compensations occur for acidosis:

  1. Respiratory compensation
  2. Metabolic compensation
A
  1. Fast - hours (respiratory rate)

2. Slow - 2-5 days (HCO3- levels)

41
Q

How is anion gap calculated?

What is the normal range?

A

AG = [Na+] + [K+] - [Cl-] - [HCO3-]
Normal range = 8 - 16

NB: sometime [K+] is not included.

42
Q

Describe the following:

  1. Anion
  2. Cation
A
  1. Anion = atoms that have gained electrons e.g. Cl-, HCO3-

2. Cation = atoms that have lost electrons e.g. Na+, K+

43
Q

What are the causes of high anion gap metabolic acidosis (GOLDMARK)?

Which is the most common cause?

A

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
Q

Give examples for the following mechanism of high anion gap metabolic acidosis:

  1. overproduction of acid
  2. underexcretion of acid
  3. cell lysis
A
  1. overproduction = ketoacidosis, lactic acidosis, alcohol, drugs
  2. underexcretion of acid = ESRF
  3. cell lysis = rhabdomyolysis
45
Q

What is the effect of hypoalbuminaemia upon anion gap (AG)?

A

1g/L drop in albumin leads to an AG increase of 2.5

46
Q

Patient with short gut syndrome may cause have a high anion gap despite a normal serum lactate, how is this possible?

A

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
Q

What are the causes of normal anion gap metabolic acidosis (HARD ASS)?

A 
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
Q

Elevation in which electroyte is often associated with normal anion gap metabolic acidosis?

What is the mechanism for acidosis?

A

Chloride - hence the term ‘hyperchloremic metabolic acidosis’

Rise in Cl- leads to drop in HCO3- and therefore acidosis.

49
Q

In normal anion gap metabolic acidosis (NAGMA), what is the urinary anion gap?

A

Calculated urinary AG = [Na+] + [K+] - [Cl-]

Usually negative in NAGMA

50
Q

What are the 2 most common causes of metabolic alkalosis?

A
  1. Loss of gastric fluid (i.e. vomiting)

2. Diuretic use

51
Q

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-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
Q

Patient has metabolic acidosis (low HCO3-), what is the approach to determining the diagnosis?

A
  1. Consider respiratory compensation:
  • expected PaCO2 = 1.5[HCO3-] + 8 +/- 2 mmHg
  • low = respiratory alkalosis
  • high = additional respiratory acidosis
  1. Calculate AG: high vs. normal
  • HIgh = MUDPILES (calculate delta-delta or osmolality gap)
  • Normal = HARD ASS (calculate urinary anion gap)
53
Q

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?

A

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
Q

Patient presents with respiratory acidosis (PaCO2 great than 42 mm Hg), what is the approach in determining the diagnosis?

A
  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.
  1. 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
Q

Patient presents with metabolic alkalosis ( [HCO3-] great than 26 mmol/L), what is the approach in determining the diagnosis?

A
  1. Consider respiratory compensation:
  • expected PaCO2 = 0.7 ( [HCO3-] - 24 ) + 40 +/- 2 mmHg
  • low = additional respiratory alkalosis
  • high = additional respiratory acidosis
  1. 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
Q

What do Bartter and Gitelman syndromes cause and how are they differentiated?

A

Both cause:
metabolic alkalosis
high urinary Cl- and urinary K+
low/normal BP

Difference:
Bartter = high urinary Ca++
Gitelman = low urinary Ca++

57
Q

PAGE 49

A

PAGE 49

NEJM Jan2014-Sep2015 (4 decks)

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