Brainscape's Knowledge GenomeTM

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


See full index

BGD > Hereditary Haemochromatosis > Flashcards

Hereditary Haemochromatosis Flashcards

1
Q

Excess iron is stored either as ferritin or ____________

A

haemosiderin.

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

What’s the bad kind of iron storage form?

Think the bad guy from toy story. Him and Sid are in there torturing toys.

A

Haemosiderin.

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

When does HH set in for men?

For women?

A

40s/50s

Women: after menopause

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

What organs are affected by iron overload?

A 
Liver
Pancreas
Heart
Skin
Gonads
Adrenal Cortex

DON’T FORGET BACTERIAL INFECTIONS

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

What’s the effect on adrenal cortex with iron overload?

A

hypocortisolism (Addison’s)

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

How can HH end up in diabetes?

A

Pancreas damage.

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

What are three things to list as liver damage in iron overload?

A

Cirrhosis
Cancer (C282Y = 20 fold risk)
hepatomegaly

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

Clinical presentation of HH is pretty non-specific. What are the two common complaints?

A

Fatigue

Arthralgia

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

What are some rarer complaints when people present with HH?

A

Cataracts
Retinal degeneration
Neuropathy (ataxia, dementia)

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

What are other frequent complaints when people present with HH?

Rhett’s cat thinks he’s a degenerate. Brain problems.

A

Cataracts
Neurological problems (ataxia, dementia)
Retinal degeneration

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

Type 1 HH is also called

A

HFE-1 haemochromatosis.

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

Short answer reminder: Two features of HFE and its C282Y mutation.

A

HFE gene is MHC-like

C282Y screws up disulfide bond in the alpha3 domain - can’t interact with B2-mic.

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

Free iron is a problem for two reasons. What are they (not haemosiderin yet)

A

Favours bacterial growth

Produces superoxides

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

Refresher: what’s transferrin?

A

Transferrin is THE transport protein for iron in the blood. Can be monoferric or diferric.

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

Refresher: what’s ferritin?

A

That’s the hollow profiterole thing that’s used for iron STORAGE.

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

What by far are the two largest iron compartments of our system?

A

Haemoglobin and Ferritin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Apart from hepatocytes, where is iron stored [in ferritin]?

A

RES Kuppfer cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

HH is primary or secondary?

A

PRIMARY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What’s an example of secondary iron overload?

A

Thalassaemia.

Also chronic liver disease and alcoholism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Briefly, how does thalassaemia lead to iron overload?

A

Circulating iron gets stolen by the erythropoietic compartment (BMP stimulation)- diferric Tf doesn’t perfuse the liver as much - HFE downregulated.
Chelation therapy preferred.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

T or F: Transferrin saturation is relatively elevated in HH.

A

FALSE (basically wrong). In HH transferrin is almost COMPLETELY SATURATED.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How much dietary iron do we absorb?

What’s the RDI?

A

Only about 10% (1-3g)

10-30g

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Why do people take vitamin C when they’re eating spinach to load up on iron?

A

Because it’s a reducing agent.

Recall absorption ferrous>ferric.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the four main players (compartment wise) in iron regulation?

A

Duodenal enterocytes
RES macrophages
Hepatocytes
RBC progenitors (marrow)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What protein represents the plasma compartment of iron?

A

transferrin.

Bonus: transferrin iron turned over 10-20 times per day.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What’s a nice term to use for an exam question on iron haemostasis?

A

FLUX. Iron is in a constant state of flux. Transferrin iron is turned over 10-20 times per day.
We absorb 1-3 mg per day 1-2mg of iron per day.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Transferrin is normally ____ saturated.

It binds _______ ferr__ ions per molecule.

A

25-50%

Ferric.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Transferrin is _________ in iron overload and _________ in iron deficiency.

A

overload: INCREASE in transferrin.
deficiency: DECREASE in transferrin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How does unsaturated transferrin protect against infection?

A

It competes for iron with iron-dependent pathogens like VIBRIO VULNIFICUS (a marine halophile).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What’s the name of the marine halophile that can infect when transferrin is saturated?

This volcano sure is nifty cos it vibrates!

A

Vibrio vulnificus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What’s the name of the marine halophile that can infect when transferrin is saturated?
No prompt

A

Vibrio vulnificus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What’s are the terms to use in the sentence about the dangers of free iron?

A

Transferrin saturation = free iron = oxidative stress and tissue damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Transferrin saturation. What’s the problem? Go.

A
  1. Vibrio vulnificus

2. Free iron (oxidative stress + tissue damage)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Three points about ferritin structure:

A
  1. 460000 kDa
  2. 4500 ferric ions storage capacity.
  3. Saturation = 30% dw is iron.
35
Q

_______ binding is favoured in high-Fe state, ______ binding is favoured in the low-Fe state.

A

High-Fe: ferritin binding

Low-Fe: transferrin binding

36
Q

How many ferric ions can make up a full chocolate centre to the ferritin profiterole?

A

4500

37
Q

IRP2 _________.
IRP1 _________.
Think response to iron.

A

IRP2 PRESERVES TfR mRNA by binding to the 3’ IRE.

IRP1 INHIBITS ferritin mRNA by binding to the 5’ IRE.

38
Q

mRNA translation starts at the _’ end and proceeds toward the _’ end.

A

Starts at 5’, ends at 3’.

Translation is 5’ to 3’.

39
Q

IRPs 1&2 bind to what kind of structures?

A

mRNA stem loops

40
Q

Together, IRPs 1IRP;2 favour…

A

… transferrin binding of iron (i.e. plasma uptake)

41
Q

What do we call the stem loops on TfR and ferritin mRNAs?

A

the 3’ and 5’ flanking iron responsive elements (IREs).

42
Q

How does high Fe favour ferritin storage?

A

Fe causes a conformation change in IRPs. No binding to IREs = degraded TfR and disinhibited ferritin translation.

43
Q

Why do we need duodenal cytochrome b ferroreductase?

Dcytbf.

A

Because ferric iron won’t be taken up by the DMT1.

44
Q

What protein is responsible for absorbing heme?

A

HCP1

Haem carrier protein 1

45
Q

Does FPN export Fe3+?

A

NO.

46
Q

HO and DMT1 both feed the ______.

A

labile iron pool (LIP).

47
Q

What two enzymes respectively provide substrates for DMT1 and HO?

A

Dcytbf

HCP1

48
Q

What’s hephaestin’s job?

A

It oxidises ferrous iron to ferric iron.

49
Q

Ferrous iron spontaneously oxidises after FPN export. T or F?

A

FALSE

It’s oxidised by hephaestin.

50
Q

What other REALLY IMPORTANT cell expresses FPN?

A

RES macrophages - therefore hepcidin also regulates liberation of RES-stored iron from storage into circulation.

51
Q

Where do RES macrophages get their iron?

A

They scavenge dead RBCs.

52
Q

Is hepcidin a hormone?

A

No.

Hormones signal

53
Q

What event in hepatocytes involves TfR2 (aot TfR1)

A

HFE binding to TfR2 initiates the BMP/SMAD signalling cascade that increases HFE expression.

54
Q

What are two other things that increase hepcidin expression?

A

Hypoxia (low O2)

IL-6 (inflammation)

55
Q

Where in the picture is haemojuvulin (Hjv) important?

A

It’s associated with TfR2 and required for BMP/SMAD signalling.
It lets BMPII&I phosphorylate SMAD1/5/8.

56
Q

Write the big complex of five major components involved in hepcidin upregulation via BMP/SMAD initiation.

A

HFE/TfR2/HJV/BMPR/BMPligand

bonus: phosphorylates SMAD1/5/8

57
Q

Name the four regulatory pathways for hepcidin expression (think of things Fe load relates to)

A

Iron status
Erythropoiesis
Inflammation
Oxygen tension

58
Q

The hypoxia aspec, the bone-morphogenetic aspect and the iron-status aspect all act through the _____ pathway.

A

BMP/SMAD

59
Q

Decreased oxygen tension leads to _______ hepcidin expression.

A

decreased hepcidin expression

60
Q

How does decreased oxygen tension increase iron intake?

A

Matriptase2 expressed
Matriptase2 cleaves HJV from the cell surface.
HJV is a BMPr coreceptor.
No BMP/SMAD pathway.

61
Q

What three proteins do you think of when you think of hypoxia?

A

HIF (hypoxia induced factor)
Furin
Matriptase 2

62
Q

IMPORTANT: what’s the hepcidin gene called?

A

HAMP.

63
Q

What pathway does inflammation (IL-6) act down?

A

JAK-STAT.

64
Q

Inflammation acts on the ___ pathway; the rest act on the ___ pathway.

A

IL-6; JAK-STAT

Else: BMP/SMAD

65
Q

The abbreviation for matriptase 2 is …

A

… TMPRSS6

66
Q

Matriptase 2 ______ HJV, while furin does what?

A

TMPRSS6 cleaves HJV preventing it’s coreceptor fucntion.

Furin cleaves is DURING PROCESSING to produce a soluble form that acts as a decoy receptor for iron.

67
Q

What’s the actual name of the BMPR ligand?

A

BMP-6.

68
Q

EXAM: R-SMAD-(P) binds to ….

A

SMAD4.

69
Q

Think hepcidin; think which STAT protein?

A

STAT6.

70
Q

The BMPr is a …

A

heterodimer made of BMPRI and II.

71
Q

IRPs are bound/unbound to Fe in order to active?

A

UNBOUND.

Fe-IRPs CAN’T bind to IREs.

72
Q

Think translational regulation; think…

A

IRPs.

73
Q

What is the name of the hormone released by RBCs in response to erythropoietin that suppresses hepcidin to enhance stress erythropoiesis?

Blood all over the floor smells bad. I’d rather smell someone’s pheromones than their penny blood.

A

Erythroferrone.

74
Q

C282Y is a ______ mutation
It is an 835 ___ mutation.
Gary hates this mutation.

A

MISSENSE

G845A

75
Q

H63D is way more ______ but way less ______ than C282Y.

A

Prevalence: H63D
Penetrance: C282Y

76
Q

Who’s more likely to get HH - a C282Y/H63D heterozygote or a H63D homozygote?

A

heterozygote.

77
Q

What’s TIBC?

A

Total iron binding capacity (transferrin saturation)

78
Q

Just cos you should know - what are the liver enzymes in routine blood tests?

A

AST, ALT

79
Q

3 things in blood tests for diagnosis.

A

TIBC (transferrin saturation)
ferritin level
liver function test

80
Q

What’s the only confirmatory test?

A

Liver biopsy - looking for iron deposition.

81
Q

What are the 5 treatments mentioned in the lecture?

A

Phlebotomy
Iron chelators
Proton pump inhibitors (decreases apical absorption).

Erythrocytaphoresis
Hepcidin agonists

82
Q

What’s that newfangled RBC removal therapy called?

A

Erythrocytaphoresis

83
Q

What are the two newfangled treatments?

A

Hepcidin agonists

Erythracytaphoresis

BGD (7 decks)

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