Brainscape's Knowledge GenomeTM

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


See full index

Metabolism > Inborn errors and diabetes > Flashcards

Inborn errors and diabetes Flashcards

1
Q

In G6P deficiency, what is the main affect?

A

Decreased production of antioxidants

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

True or false, G6P deficiency results in increased concentrations of 6-phosphogluconolactone

A

False

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

Type III Cori’s disease is a Glycogen Storage Disorder due to a mutation in

A

De-branching enzyme

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

What length of FA chains does MCAD break down?

A

4-12 carbons long

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

What does MCAD stand for?

A

Medium Chain Acyl CoA Dehydrogenase

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

Patients with Glycogen Storage Disorder Type V McArdle’s disease present with?

A

Exercise intolerance

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

Is carnitine received exclusively from the diet?

A

No

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

Who demonstrated that removal of the pancreas in dogs lead to diabetes?

A

Oscar Minkowski

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

Which 4 factors contributes to hyperglycaemia in type 1 diabetes?

A

Increased glycogenolysis

Decreased glucose uptake

Increased gluconeogenesis

Increased proteolysis

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

What is an inborn error of metabolism?

A

Genetic disease

Mutation in a metabolic protein that changes its function

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

Why can inborn errors of metabolism be difficult to screen and understand?

A

Perceived build up of reactants may be offset by alternative reactions using them up

Perceived loss of products may be offset by other pathways feeding in to produce them

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

What is MCAD deficiency?

A

Deficiency in medium chain Acyl CoA Dehydrogenase which catalyses the first oxidation reaction of fatty acid oxidation.

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

What does MCAD result in?

A

Cant breakdown FA when fasting

No ketogenesis on fasting = hypoketotic on fasting

Fasting hypoglycaemia as more dependent on glucose

Vomiting, lethargy, seizure, coma and death

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

What is carnitine deficiency, what does it affect?

A

Deficiency of carnitine, does not bind with fatty acetyl CoA so it cannot enter the mitochondria via the carnitine shuttle, therefore fatty acids cant be oxidised.

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

What are the symptoms of carnitine deficiency?

A

Presents with cardiomyopathy

Presents with fatty infiltration of organs

Muscle weakness

50% have hypoglycaemia

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

What is the role of peroxisomes in FA metabolism?

A

Peroxisomes catalyse initial steps in oxidation of Very Long Chain Fatty Acids, prior to transport to the mitochondria.

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

What happens to peroxisomes in zellwegers disease?

A

Defect in import of proteins into peroxisome – “ghost peroxisomes” that consist of membrane but no protien

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

What are the symptoms of peroxisomal disorders?

A

Hypotonia and seizures

Abnormal facial presentation

Hepatomegaly, renal cysts, adrenal hypoplasia

Neonatal onset, usually death within months

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

How is G-6-P dehydrogenase deficiency inherited?

A

X-linked

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

What is G-6-P dehydrogenase?

A

Enzyme is first step in the PPP, converts G-6-P to 6-phosphogluconolactone

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

What does G-6-P dehydrogenase deficiency lead to?

A

Less able to generate NADPH

Cannot overcome oxidative stress

Ezymes and other proteins (including hemoglobin) are subsequently damaged by the oxidants, leading to cross-bonding and protein deposition in the red cell membranes.

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

Why are red cells mainly affected by G-6-P dehydrogenase deficiency ?

A

No mitochondria so no means of aerobic respiration

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

What are the three glycogen storage diseases?

A

Type I Von Gierke’s Disease Glucose-6-phosphatase deficiency

Type III Cori’s Disease Debranching enzyme deficiency

Type V McArdle’s disease Muscle phosphorylase deficiency

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

What is deficient in Type I Von Gierke’s disease?

A

Glucose-6-phosphatase deficiency

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

What is deficient in Type III Cori’s disease

A

Debranching enzyme deficiency

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

What is deficient in Type V McArdle’s disease?

A

Muscle phosphorylase deficiency

27
Q

What is the effect of Type I Von Gierke’s disease?

A

Enzyme in liver endoplasmic reticulum

Can’t dephosphorylate liver glucose-6-phosphate, so cant increase blood glucose from glycogen (glycogenolysis)

Histology shows massive glycogen accumulation - enlarged liver and kidneys

Blood glucose concentration low (~ 2 mmol/l) - hypoglycaemia

Lactic acidaemia

28
Q

What are the effects of Type III Cori’s disease?

A

Enzyme in liver and muscle – removes branches off glycogen

The structure of both liver and muscle glycogen is abnormal

Results in an increased amount of glycogen with short outer branches

29
Q

What are the effects of Type V McArdle’s disease?

A

Enlarged glycogen granules in muscle

In response to exercise the muscle cant use glycogen for ATP production

Exercise intolerance and painful cramps

30
Q

Is liver glycogen affected in Type V McArdles disease?

A

Only phosphorylase isoform in muscle is absent

Blood glucose and liver not compromised

31
Q

What is phenylketonuria?

A

PKU is caused by deficiency of Phenylalanine Monooxygenase (aka phenylalanine hydroxylase).

Unable to metabolise phenylalanine

32
Q

What is the most common inborn error of metabolism?

A

Phenylketonuria

33
Q

Why does PKU affect the brain?

A

Toxic metabolite theory: the new metabolites phenylpyruvate and phenyllactate are responsible for brain damage

Transport hypothesis: phenylalanine at high concentrations outcompetes other molecules for uptake into the brain - brain damage

34
Q

What does PKU lead to?

A

Neurological damage – low IQ, behavioural difficulties

35
Q

How is PKU treated?

A

Phenylalanine-free diet/low protein diet.

36
Q

What is galactosaemia?

A

Deficiency in galactose-1-phosphate uridyltransferase

37
Q

What does galactosaemia lead to?

A

Inability to digest galactose (lactose is glucose+galactose)

Newborn milk is rich in lactose

First milk ingestion causes:
Vomiting and failure to thrive, Delayed development, Severe liver disease Cataracts

38
Q

How is galactosaemia treated?

A

Galactose-free diet

39
Q

What is hereditary fructose intolerance?

A

Deficiency in Fructose-1-phosphate aldolase

40
Q

What does hereditary fructose intolerance lead to when fructose is ingested?

A

Consumption of fructose causes accumulation of fructose-1-phosphate in liver

This process sequesters inorganic phosphate = hypophosphataemia

F-1-P inhibit the “traditional” aldolase in glycolysis/gluconeogenesis.

Also inhibits glycogen phosphorylase.

This means F-1-P inhibits both gluconeogenesis and glycogenolysis = hypoglycaemia.

Acute exposure to fructose causes sweating, dizziness, nausea, seizures and coma

Chronic exposure causes failure to thrive, vomiting, drowsiness, hepatomegaly

41
Q

What is diabetes mellitus?

A

Metabolic disorders characterized by a high blood sugar level over a prolonged period of time.

42
Q

What is type 1 diabetes?

A

Auto-immune destruction of pancreatic β-cells

Less/no insulin is produced

43
Q

What is type 2 diabetes?

A

Insulin resistance – defective sensitivity of peripheral tissues to insulin

Can lead to defect in insulin secretion

44
Q

How is diabetes tested for?

A

Glucose tolerance test

45
Q

Describe the rough procedure for the glucose tolerance test

A

A zero time (baseline) blood sample is drawn.

The patient is then given a measured dose of glucose solution to drink within a 5-minute time frame.

Blood is drawn at intervals for measurement of glucose (blood sugar), and sometimes insulin levels.

46
Q

What is a normal fasting plasma glucose?

A

~4mmol/L

Below 5.6 mmol/L.

47
Q

What are fasting plasma glucose levels that indicate diabetes or pre diabetes?

A

5.6 - 6.9 mmol/L indicate prediabetes

Above 7.0 mmol/L diagnostic of diabetes.

48
Q

For a 2 hour GTT with 75 g intake, what is normal prediabetic and diabetic glucose concentration?

A

Below 7.8 mmol/L is normal.

Between 7.8 mmol/L - 11.1 mmol/L - prediabetic

Above 11.1 mmol/L confirm a diagnosis of diabetes.

49
Q

What are the blood characteristics of an individual with type I diabetes?

A

Insulin levels are low, thus when glucose is ingested, glucose concentration remains high in the blood

50
Q

What is the metabolic profile of a type 1 diabetic similar to?

A

Metabolic profile of a type 1 diabetic is one of a person in starvation.

Low insulin (Hypoinsulinaemia) 
High glucose (Hyperglycaemia) 
High lipids (Hyperlipidaemia) 
High ketones (Hyperketonaemia)
51
Q

Why is polyuria a symptom of type I diabetes, how does it arise?

A

Plasma glucose concentrations rise: When exceeds renal threshold (>12 mmol/l) glucose is excreted in the urine

This makes the urine hyperosmolar

Therefore, additional water is excreted

This results in dehydration and thirst.

52
Q

Why is ketoacidosis a symptom of type I diabetes?

A

Low insulin, ketogenesis promoted

53
Q

What does ketoacidosis lead to?

A

Ketone bodies are acids

Overwhelms bicarbonate buffering system

Therefore, try to compensate by increased ventilation (respiratory alkalosis) leads to Kussmaul respiration

Smell of acetone

Dehydration (give fluids).

54
Q

What are some long term complications of type I diabetes?

A

Microvascular and macrovascular complications
Cardiovascular disease

Nephropathy
Retinopathy
Neuropathy

Amputation
Depression and Dementia

Complications in pregnancy

Sexual dysfunction

55
Q

What are treatment options for type I diabetes?

A

Glucose monitoring: Blood glucose meters using a drop of blood, Continuous glucose monitoring (interstitial fluid)

Insulin injections

Subcutaneous insulin infusion = insulin pumps

Islet transplantation

56
Q

What elements of a blood sample are idicative of type II diabetes?

A

Hyperinsulinaemia but can lead to hypoinsulinaemia ( β-cell not being able to produce this increased amount of insulin )

Hyperglycaemia

57
Q

What are 4 possible mechanisms behind type 2 diabetes?

A

Adipokines (adipose derived inflammatory cytokines) secreted from enlarged adipose tissue

Intracellular lipid accumulation in peripheral tissues: lipotoxicity

High glucose: glucotoxicity

Adipose derived hormones

58
Q

What is initial treatment for type 2 diabetes?

A

Lifestyle changes

59
Q

What are some pharmacological interventions for type 2 diabetes?

A

Metformin (biguanides) (improve insulin sensitivity)

SGLT2 inhibitors: increase glucose renal excretion

Insulin injections if β-cell function decreases

60
Q

A potentially serious complication of uncontrolled type I diabetes is metabolic acidosis which results in…

A

Hyperkalaemia

61
Q

In liver disease, what will be elevated in the blood?

A

Ammonia, serum bilirubin, aspartate aminotransferase

62
Q

In liver disease, what is depressed in the blood?

A

Glucose, hypoglycaemia

63
Q

What is a potentially life-threatening consequence of liver disease?

A

Coagulopathy (insufficient clotting proteins)

64
Q

What three features are noticed in clinical examination of liver disease?

A

Jaundice, ankle oedema and bruising

Metabolism (13 decks)

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