M104 T2 L13 Flashcards
1
Q
What are the symptoms of hypoglycaemia?
A
moodiness, faintness, numbness in arms and hands, blurred vision, confusion, memory loss, dizziness or lethargy that may progress to coma
2
Q
What does hypoglycaemia have the same effects as?
A
cerebral anoxia
3
Q
What are the serious consequences of hypoglycaemia?
A
loss of cognitive function, seizures and coma
4
Q
At what blood glucose level is loss of consciousness achieved?
A
at 2.5 mM (45 mg/dL)
5
Q
How is hypoglycaemia treated?
A
via the rapid restoration of blood glucose
by i.v. glucose or injection of glucagon
6
Q
What is the effect of prolonged or repeated hypoglycaemia?
A
permanent brain damage
7
Q
What is the criteria for hypoglycaemia?
A
having a blood glucose level of below 4 mM (72 mg/dL)
8
Q
When might symptoms of hypoglycaemia develop?
A
at higher levels than 4 mM if there is rapid fall of previously elevated levels, although some individuals may show no effects even below 4 mM
9
Q
What are the potential effects of a rapid fall in blood glucose levels?
A
sweating, tachycardia and agitation
10
Q
What are the potential effects of a rapid fall in blood glucose levels caused by?
A
the activation of the sympathetic NS system and release of adrenaline & glucagon
11
Q
How does hypoglycaemia present in healthy individuals and what might it be caused by?
A
presents as a mild case
cause - fasting or over exercise
12
Q
What are the main causes of hypoglycaemia?
A
fasting or over exercise
excess of exogenous insulin / insulinoma
inhibition of endogenous glucose production
13
Q
What is an example of a condition caused by Hypernatraemia?
A
diabetes insipidus
14
Q
What are two examples of factors that can cause Hypovolaemia?
A
vomiting, dehydration
15
Q
What’s an example of a pathology that can cause Hypovolaemia?
A
adrenal insufficiency
16
Q
What are the lesser causes of hypoglycaemia?
A
Hypernatraemia
Hypovolaemia
certain pathologies
17
Q
What might cause the inhibition of endogenous glucose production?
A
excess alcohol
18
Q
How long does it take for alcohol-induced hypoglycaemia to occur after alcohol ingestion?
A
several hours
19
Q
When does alcohol-induced hypoglycaemia occur?
A
on the depletion of glycogen stores, when the blood glucose levels are reliant on hepatic gluconeogenesis
20
Q
What is the effect of alcohol-induced hypoglycaemia in the short term (24hrs)?
A
it places additional stresses on gluconeogenesis, as alcohol is metabolised primarily in the liver by an unregulated process
21
Q
What is the effect of alcohol-induced hypoglycaemia in the long-term (years)?
A
gluconeogenesis may also be decreased by liver damage and reduced muscle mass
22
Q
What happens to ethanol in the liver?
A
it is rapidly metabolised by alcohol dehydrogenase (enzyme)
23
Q
What is the structural formula of ethanol?
A
C2H2OH
24
Q
What is the structural formula of acetaldehyde?
A
CH3CHO
25
What substance is involved in the conversion of ethanol to acetaldehyde?
the co-enzyme NAD+, which is reduced to NADH
26
What enzyme catalyses the conversion of ethanol to acetaldehyde?
alcohol dehydrogenase
27
What is the side-effect of the conversion reaction of ethanol to acetaldehyde?
there will be a high NADH:NAD+ ratio in cytosol
28
What happens to acetaldehyde produced from ethanol in the liver?
it is transported into the mitochondria where it is oxidised to acetate by acetaldehyde dehydrogenase
29
What is acetaldehyde converted into?
it is oxidised to acetate
30
What is the role of acetaldehyde dehydrogenase?
to catalyse the oxidation of acetaldehyde to acetate
31
What is acetate otherwise known as?
acetic acid
32
What is the structural formula of acetic acid?
CH3COOH
33
What are the metabolic consequences of ethanol metabolism in the liver?
it increases NADH + H+ and shifts the EQL of the reactions above
Reduces the availability of substrates for entry into gluconeogenesis to maintain plasma glucose levels
34
Why does alcohol-induced hypoglycaemia occur?
when ethanol is ingested when the bgc is reliant on gluconeogenesis
35
What are the effects of alcohol-induced hypoglycaemia?
rapid heartbeat, clammy skin
| rapid breathing
36
What causes the effects of alcohol-induced hypoglycaemia?
a fall in blood glucose leads to a stress response in an effort to enhance the stimulation of gluconeogenesis by combined action of glucagon and adrenaline
37
Why is rapid breathing an effect of alcohol-induced hypoglycaemia?
bc it is a physiologic response to metabolic acidosis
38
What is rapid breathing in alcohol-induced hypoglycaemia caused by?
an excess of lactic acid
39
What are the effects of long-term alcohol consumption on lipid metabolism?
high levels of NADH inhibit FA oxidation; instead the excess NADH signals that conditions are right for FA synthesis
TGs accumulate in the liver causing ‘fatty liver’
TGs are exported as VLDL
40
What are the three stage of fatty liver disease? (SFC)
steatohepatitis
fibrosis
cirrhosis
41
What happens during the cirrhosis stage of fatty liver disease?
extensive scar tissue replaces healthy tissue
42
What happens during the fibrosis stage of fatty liver disease?
scar tissue forming at sites of damage
43
What happens during the steatohepatitis stage of fatty liver disease?
damage is caused to the liver by inflammation
44
What can acetate produced from EtOH be converted into?
acetyl-CoA
45
What happens to acetyl-CoA after it is produced from acetate?
its further processing in TCA cycle is prevented
46
Why is the further processing of acetyl-CoA in the TCA cycle prevented?
bc high levels of NADH inhibits both citrate synthase and α-ketoglutarate dehydrogenase
47
What are the two effects of acetyl CoA accumulation?
ketone bodies are produced
| acetaldehyde build-up
48
What happens to ketone bodies produced
which are released into the blood and exacerbates the already acidic conditions resulting from high lactate levels
49
What causes a build-up of acetaldehyde?
when the processing of acetate in the liver becomes inefficient
50
Why is a build-up of acetaldehyde bad?
it is is highly toxic
51
What is the effect of alcohol consumption on proteasomes?
it decreases their activity
52
What happens when the activity of proteasomes is decreased?
protein accumulates, causing liver enlargement increases oxidative stress
53
What is a feature of people with chronic alcoholism?
they frequently have deficient intakes of micronutrients and minerals
54
What are examples of minerals that people with chronic alcoholism are often deficient in?
zinc and selenium
55
What percentage of alcoholics with liver disease will have thiamine deficiency?
50%
56
What are the symptoms of alcohol-induced thiamine deficiency?
anorexia, irritability, and difficulties with short-term memory
57
What are the causes of alcohol-induced thiamine deficiency?
Malnourishment
Ethanol interferes with GI absorption
Hepatic dysfunction, which hinders storage and activation to thiamine pyrophosphate
58
What is the half life of thiamine?
10-20 days
59
What is the consequence of thiamine having a short half life?
deficiency can occur rapidly during depletion
60
How do the types of Glycogen storage diseases differ?
they depend on which enzyme is affected
61
What are the stores of glycogen are affected by in Glycogen storage diseases?
by defects in either the enzymes of synthesis or degradation of glycogen
62
What are the genetics for all of the Glycogen storage diseases?
autosomal recessive
63
What is the Glycogen storage disease that is genetically exceptional?
type IX which is sex-linked, not autosomal recessive
64
What are the effects of Glycogen storage disease?
they all result in the production of an abnormal amount or abnormal type of glycogen
65
What is the frequency of Glycogen storage disease?
1:20000-1:40000 births
66
What are the effects of Glycogen storage disease??
May affect any of the enzymes involved in glycogen synthesis and breakdown
67
What organs are mainly affected by Type I GSD?
liver and kidneys
68
What is Type I GSD caused by?
a deficiency in G-6-Pase
69
What is Type II GSD caused by?
a deficiency of a-1,4 glucosidase activity in the lysosomes
70
Which is one of the most devastating of the glycogen storage diseases?
Type II. Pompe’s disease
71
What is the end result of severe Type II GSD?
death by cardiorespiratory failure
72
What is Type III Cori’s disease caused by?
a deficiency of debranching enzyme
73
What is de-branching enzyme otherwise known as?
amylo 1,6 glucosidase
74
What is the effect of Type III GSD?
an inability to break down glycogen, resulting in hypoglycaemia
75
What is the strange about the symptoms of Type III GSD?
the symptoms often disappear at puberty
76
Which is one of the most severe of the glycogen storage diseases?
Type IV Andersen’s disease
77
What is Type IV GSD caused by?
branching enzyme is affected
78
What is the life expectancy for Type IV GSD?
five years
79
What is Type V GSD caused by?
muscle (not liver) glycogen phosphorylase is damaged so that muscle cannot break down accumulating glycogen
80
What is the effect of Type V GSD?
a low tolerance to exercise and fatigue easily, with painful muscle cramps after exercise
81
What is the life span for Type V GSD?
normal
82
What is the most common Glycogen storage disease and to what proportion?
Von Gierke's Disease - 25%
83
What is Von Gierke's Disease caused by?
a deficiency of glucose-6-phosphatase in liver, kidneys and intestines
84
What is Von Gierke's Disease otherwise known as?
Type 1 Glycogen storage disease
85
What reactions are catalysed by G-6-P?
the terminal reaction of glycogenolysis and gluconeogenesis
86
What are the effects of Von Gierke's Disease?
the impaired export of glucose from the liver from these two pathways between meals causes hypoglycaemia that does not respond to glucagon
87
When do the symptoms of Von Gierke's Disease appear?
when intervals between feeds increases and infants sleep through the night, or when illness prevents normal feeding routine
88
What is the effect of a lack of G-6-P in Von Gierke's Disease?
means that glucose cannot be exported from the liver.
results in high levels of G-6-P in the liver & kidney
G-6 is metabolized to lactic acid or converted to glycogen or lipid
89
What are the effects of high levels of G-6-P in the liver & kidney in Von Gierke's Disease?
abnormal levels of glycogen accumulation in the liver and kidney – causing enlargement of the liver and kidneys
Increased glycolysis leading to lactic acidosis
Increased FA, TG and VLDL synthesis and excretion
90
How does the body attempt to compensate for hypoglycaemia in Von Gierke's Disease?
by releasing glucagon (hyperglucagonaemia) and adrenaline resulting in mobilisation of fat stores and release of FAs
91
What is the effect of the conversion of FAs to TGs and VLDL in the liver in Von Gierke's Disease?
accumulation of fat in liver and hyperlipidaemia
May lead to hepatoma
accumulation of fat in cheeks and buttocks.
92
What are the effects of Von Gierke's Disease on the patient?
enlarged livers and/or kidneys
stunted growth, severe tendencies to hypoglycaemia (convulsions)
hyperlactaemia and hyperlipidemia.
May also have hyperuricaemia as a result of hyperlactaemia as lactic acid in the blood competes for kidney transport mechanisms
93
What is the aim of treatment in Von Gierke's Disease?
to correct hypoglycaemia and maintain normoglycaemia
94
What is the treatment in Von Gierke's Disease for young infants?
they are fed glucose through nasogastric tubes
95
What is the treatment in Von Gierke's Disease for older children?
glucose drinks at 2-3 hour intervals night and day to prevent fall in blood glucose and cerebral damage.
Uncooked corn starch may be used to prolong period between feeds
Restrict dietary lipids
Liver transplant
96
What are the products of the reversible reaction lactate + NAD+?
pyruvate + NADH + H+
97
What are the products of the reversible reaction of malate + NAD+?
OAA + NADH + H+
98
What are the products of the reversible reaction of G3P + NAD+?
DHAP + NADH + H+
99
What three metabolic reactions are affected by alcohol metabolism in the liver?
pyruvate + NADH + H+ = lactate + NAD+
OAA + NADH + H+ = malate + NAD+
DHAP + NADH + H+ = G3P + NAD+
100
How are the three metabolic reactions changed by alcohol metabolism in the liver?
it drives these reactions in the direction that alleviates the high NADH to NAD+ ratio
101
What is the effect of high NADH levels caused by alcohol metabolism?
causes the three reactions to be driven in the direction by which NADH+ is produced from NADH + H+
102
Why do high NADH levels result in increased NAD+ production in alcohol metabolism?
EQL - trying to redress that balance of the high NADH to NAD+ ratio by re oxidising NADH back to NAD+
103
What are the effects of high NADH levels resulting in its conversion to NAD+ in alcohol metabolism?
shortage of pyruvate and OAA in the cell
these are substrates for gluconeogenesis.
so the cells are deprived of these raw materials for gluconeogenesis
104
What is the biochemistry behind how ethanol in hepatocytes is converted to acetate?
via portal circulation, ethanol enters the hepatocyte < acetaldehyde via acetaldehyde dehydrogenase (NAD+ < NADH)
acetaldehyde enters the mitochondria < acetic acid (dissociates) < acetate and H+ (NAD+ < NADH)
increased ROS levels produced in the mitochondria, these can damage nucleic acids, proteins and lipids.
105
What type of reaction is the conversion of NAD+ to NADH?
reduction
106
What happens to the acetate produced in the mitochondria during the metabolism of alcohol?
some is exported from the liver for use by other tissues
| most is converted to acetyl coenzyme A
107
What happens to the acetyl coenzyme A produced from acetate during the metabolism of alcohol?
it is used to synthesise ketone bodies, which are secreted into the blood from the liver.
108
What reaction occurs due to high levels of NADH and of acetyl-CoA?
FA synthesis which generates TGCs
some are stored and may generate fatty liver condition
some are packaged into VLDL and are exported into the blood = hyperlipidaemia
109
What happens to the pyruvate generated by glucose and amacs during the metabolism of alcohol?
it's converted to lactic acid, which is secreted into the blood where it can cause lactic acidaemia
110
What is Type IV GSD caused by?
the presence of long unbranched chains of liver glycogen (in normal amounts) that have low solubility
111
What is Type II GSD otherwise known as?
Pompe’s disease
112
What is Type III GSD otherwise known as?
Cori’s disease
113
What is Type IV GSD otherwise known as?
Andersen’s disease
114
What is Type V GSD otherwise known as?
McArdle’s syndrome
