Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Chem Path - Laz > Chem Path 8 - Porphyrias > Flashcards

Chem Path 8 - Porphyrias Flashcards

You may prefer our related Brainscape-certified flashcards:
Periodic Table flashcards Chemistry 101 flashcards AP® Chemistry flashcards Organic Chemistry 101 flashcards
1
Q

What is porphyria?

A

Disorders caused by deficiencies in enzymes of the haem synthesis pathway

This leads to the accumulation of toxic haem precursors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the two ways in which porphyria can manifest?

A

Acute neuro-visceral attacks

Acute or chronic cutaneous symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List some key features of haem.

A

Organic heterocyclic compound with Fe2+ in the centre

There is a tetrapyrrole ring around the iron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where is haem found?

A

Erythroid cells

Liver cytochrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which component of this pathway is neurotoxic?

A

5-ALA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What types of porphyrin may be produced in the absence of iron?

A

Metal-free protoporphyrins

Zinc protoporphyrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How can porphyrias be classified?

A

Principle site of enzyme deficiency

· Erythroid

· Hepatic

Clinical presentation

· Acute or non-acute

· Neurovisceral or skin lesions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Outline the relationships between UV light and skin lesions.

A

Porphyrinogens are oxidised and then activated by UV light into activated porphyrins

NOTE: porphyrinogens do NOT oxidise in cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is a key difference between porphyrinogens and porphyrins?

A

Porphyrinogens – colourless, unstable and readily oxidised to porphyrin

Porphyrins – highly coloured

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which porphyrins appear in the urine and faeces

A

Urine – uroporphyrins are water soluble

Faeces – coproporphyrins are less soluble and near the end of the pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

List four types of acute porphyria and the enzymes involved.

A

Plumboporphyria – PBG synthase

Acute intermittent porphyria – HMB synthase

Hereditary coproporphyria – coproporphyrinogen oxidase

Variegate porphyria – protoporphyrinogen oxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

List three types of non-acute porphyria and the enzymes involved.

A

Congenital erythropoietic porphyria – uroporphyrinogen III synthase

Porphyria cutanea tarda – uroporphyginogen decarboxylase

Erythropoietic protoporphyria – ferrochetolase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the most common type of porphyria?

A

Porphyria cutanea tarda

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the most common type of porphyria in children?

A

Erythropoietic protoporphyria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does ALA synthase deficiency cause?

A

X-linked sideroblastic anaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How can a mutation in ALA synthase lead to porphyria?

A

A gain-of-function mutation will result in increased throughput through the pathway leading to a build-up in protoporphyrin IX as it overwhelms the ability of ferrochetolase to convert it into haem

17
Q

What are the main features of PBG synthase deficiency?

A

Causes acute porphyria

Leads to accumulation of ALA

Abdominal pain (most important feature)

Neurological symptoms (e.g. coma, bulbar palsy, motor neuropathy)

18
Q

Which deficiency causes acute intermittent porphyria?

A

HMB synthase (aka PBG deaminase)

19
Q

Outline the clinical features of acute intermittent porphyria.

A

Rise in PBG and ALA

Autosomal dominant

Neurovisceral attacks

· Abdominal pain

· Tachycardia and hypertension

· Constipation, urinary incontinence

· Hyponatraemia and seizures

· Sensory loss/muscle weakness

· Arrhythmias/cardiac arrest

IMPORTANT: there are NO skin symptoms (because no porphyrinogens are produced)

NOTE: 90% will be asymptomatic

20
Q

List some precipitating factors for acute intermittent porphyria.

A

ALA synthase inhibitors (e.g. steroids, ethanol, anticonvulsants (CYP450 inducers))

Stress (infection, surgery)

Reduced caloric intake

Endocrine factors

21
Q

Describe how acute intermittent porphyria is diagnosed.

A

Increased urinary PBG (and ALA)

PBG gets oxidised to porphobilin

Decreased HMB synthase activity in erythrocytes

22
Q

How is acute intermittent porphyria managed?

A

Avoid attacks (adequate nutrition, avoid precipitant drug, prompt treatment of other illnesses)

IV carbohydrate (inhibits ALA synthase)

IV haem arginate (switches off haem synthesis through negative feedback)

23
Q

Name two acute porphyrias that have skin manifestations. State the enzymes affected.

A

Hereditary coproporphyria - coproporphyrinogen oxidase

Variegate porphyria – protoporphyrinogen oxidase

24
Q

What is the negative consequence of accumulation of coproporphyrinogen III and protoporphyrinogen IX?

A

They are potent inhibitors of HMB synthase

Results in the accumulation of PBG and ALA

25
Q

What are the main clinical features of hereditary coproporphyria?

A

Autosomal dominant

Acute neurovisceral attacks

Skin lesions (blistering, skin fragility, classically on the backs of the hands that tend to appear hours/days after sun exposure)

26
Q

What are the main clinical features of variegate porphyria?

A

Autosomal dominant

Acute attacks with skin lesions

27
Q

How is the porphyrin level in the urine and faeces different in hereditary coproporphyria and variegate porphyria compared to acute intermittent porphyria?

A

AIP - normal

HCP and VP – high

NOTE: DNA analysis offers a definitive diagnosis

28
Q

What is a common feature of non-acute porphyria?

A

Only present with skin lesions with NO neurovisceral manifestations

29
Q

List the enzymes associated with non-acute porphyria.

A

Uroporphyrinogen III synthase – congenital erythropoietic porphyria

Uroporphyrinogen decarboxylase – porphyria cutanea tarda

Ferrochetolase – erythropoietic protoporphyria

30
Q

What is the main clinical feature of non-acute porphyria?

A

Skin blisters, fragility, pigmentations and erosions

Occurring hours to days after sun exposure

31
Q

What are the key features of erythropoietic protoporphyria?

A

NON-blistering and presents with photosensitivity, burning, itching, oedema following sun exposure

32
Q

What is a key investigation for erythropoietic protoporphyria?

A

RBC protoporphyrin

33
Q

What are the key features of porphyria cutanea tarda?

A

Can be inherited or acquired

Leads to formation of vesicles on sun-exposed areas of skin crusting, superficial scarring and pigmentation

34
Q

Outline the biochemistry features of porphyria cutanea tarda.

A

Urine/plasma uroporphyrins and coproporphyrins are raised

Ferritin is often increased

35
Q

Which drug can trigger porphyria cutanea tarda?

A

Hexachlorobenzene

36
Q

What haematological condition are erythropoietic protoporphyria and congenital erythropoietic porphyria associated with?

A

Myelodysplastic syndromes

37
Q

During acute porphyria, what is the most useful sample to send?

A

Urine

Chem Path - Laz (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions