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MD2002 Lucas > Metabolic Changes in Health and Disease > Flashcards

Metabolic Changes in Health and Disease Flashcards

1
Q

What happens when glucose levels are too high ?

A

Starts appearing in urine

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2
Q

What happens when glucose levels are too low ?

A

Gluconegenesis

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3
Q

Which proportion of glucose absorbed after a meal travels to the liver in the hepatic portal system ?

A

95%

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4
Q

What proportion of the glucose in the liver is metabolise in the liver and which proportion continues on, to be distributed to other tissues ?

A

35% metabolised in the liver

65% continues on, to be distributed to other tissues

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5
Q

What are the two states of metabolism ?

A

Fed (absorptive) - new nutrients available

Fasted (post-absorptive) - draws upon fuel stores

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6
Q

In fed state, is metabolism anabolic or catabolic ? What happens in this state ?

A

ANABOLIC
Nutrient molecules are used to 1. provide energy stores (stored) or to 2. provide needs of growth and maintenance of cells and tissues (used immediately)

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7
Q

In fasted state, is metabolism anabolic or catabolic ? What happens in this state ?

A

CATABOLIC

Body draws upon energy stores

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8
Q

What are some factors which determine the rate of metabolic reactions ?

A

Concentrations of substrates and products (direct or downstream)
Activity of the relevant enzymes
Hormones (affect some enzymes)

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9
Q

What are the key hormones involved in regulating metabolism ?

A

Insulin
Glucagon
Adrenaline (epinephrine)
Noradrenaline (norepinephrine)

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10
Q

What kinds of modifications alter enzyme activity ?

A

-Actions mediated by activation of intracellular protein kinases and phosphorylation of key regulatory proteins on tyrosine, serine or threonine residues (covalent modifications)

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11
Q

Is most of the pancreas exocrine or endocrine ? What proportion of its mass is made of up endocrine cells ?

A

Exocrine

2%

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12
Q

What are the exocrine cells of the pancreas ? What does each secrete ?

A

Alpha cells- Glucagon
Delta cells- Somatostatin
Beta cells- Insulin

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13
Q

What change in glucose level stimulates insulin secretion ? Which NS is responsible for stimulation of beta cells ?

A

Elevated blood [glucose]

PSNS

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14
Q

What is insulin’s main function ?

A

Stimulates storage of fuels and anabolism.

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15
Q

What are some of the metabolic effects of insulin ?

A
  1. Stimulates glycogen synthesis in liver and muscle
  2. Stimulates uptake of glucose into muscle and adipose tissue
  3. Stimulates glycolysis (glucose oxidation) and hence fatty acid synthesis in liver
  4. Stimulates fat synthesis
  5. Stimulates protein synthesis in muscle
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16
Q

What change in glucose level stimulates glucagon secretion ?

A

Decreased blood [glucose]

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17
Q

What organ is the main target for glucagon ?

A

Liver

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18
Q

What are some of the metabolic effects of glucagon ?

A
  1. Stimulates release of glucose from glycogen (glycogenolysis)
  2. Stimulates gluconeogenesis but inhibits glucose incorporation into glycogen (gluconogenesis)
  3. Stimulates breakdown of triglycerides in fat tissue (ketogenesis)
19
Q

What exactly is it that determine whether metabolism is in the fed or fasting state ?

A

The balance between circulating levels of insulin and glucagon. If insulin > glucagon, Fed. If glucagon > insulin, Fasted.

20
Q

Where are ADRENALINE AND NORADRENALINE secreted ? When ?

A

By the adrenal medulla and neurones of the sympathetic

nervous system when blood [glucose] falls.

21
Q

What are some of the metabolic effects of adrenaline and noradrenaline ?

A
  • Stimulates breakdown of glycogen (mainly on muscle (producing glucose-6-P) rather than on liver) and triglycerides
  • Lower glucose uptake by muscle, so FAs released by adipose tissue used as fuel
  • Increase glucagon secretion and inhibit insulin secretion
22
Q

What is the normal blood range before a meal ? After a meal ?

A

80 mg/100 ml before a meal

120 mg/100 ml after a meal

23
Q

What two factors are key to keeping blood glucose levels within narrow limits ?

A
  1. Liver: It can take up and release large amounts of glucose
  2. Relative concentrations of insulin and glucagon
24
Q

What is the blood glucose concentration in hyperglycaemia ?
in hypoglycaemia ?
What is the normal blood glucose concentration (mmol/L)

A

> 11 mmol/litre
<3 mmol/litre
4-8 mmol/litre

25
Q

What is the total amount of carbs, proteins, and fats (all together) which the body stores and can draw from in times of need ?

A

Approximately 162 000 kcal

26
Q

What extended period of starvation are the fuel stores sufficient for ?

A

1 to 3 months, depending on level of activity

27
Q

What happens during the first days of starvation to brain, muscle and liver ?

A
  • Carb stores only last a day or less (depending on activity level) so blood glucose levels fall
  • BRAIN: completely dependent on glucose, metabolism must adjust itself to maintain [glucose] at an adequate level: triglycerides have a limited ability to be converted to glucose BUT proteins potentially can yield glucose (gluconeogenesis) but these need to be preserved as much as possible
  • MUSCLE: begins using FAs (released from ADIPOSE TISSUE) instead of glucose (leaves more glucose to brain)
  • LIVER: uses fats mobilized from adipose tissue and pyruvate, lactate and alanine (from breakdown of protein) from muscle to make as much glucose as possible for export into the blood (for BRAIN)
28
Q

What happens during the later stages of starvation to brain, muscle and liver ?

A

After about 3 days:
LIVER: large amounts of ketone bodies begin to be formed by liver (due to limitations in the activity of the TCA cycle)
BRAIN: becomes more tolerant of lowered blood [glucose] and gains the ability to use ketone bodies. Ability of the brain to use ketone bodies gradually increases over weeks of starvation, so the need for glucose is lowered.
MUSCLE: body uses less glucose, so the need for amino acids to fuel gluconeogenesis is also reduced so there is a reduction in the rate at which muscle is broken down

29
Q

What are some symptoms of untreated diabetes ?

A
  • Excessive urination
  • Excessive thirst
  • Body wasting due loss of muscle and fat tissue
  • Hunger
30
Q

What is the commonest serious metabolic disease ?

A

Diabetes Mellitus

31
Q

Name the types of diabetes and at which stage of life each one occurs.

A

Type 1- Insulin-dependant (juvenile onset)

Type 2- non-insulin-dependant = insulin resistant (adult onset)

32
Q

What are the main features of type 1 diabetes ?

A
  • Autoimmune disease
  • β-cells of pancreas are destroyed (so not much insulin can be secreted in response to rise in blood [glucose].
  • Glucose cannot be taken up by cells and so remains in the blood)
33
Q

What percentage of diabetes cases does Type 1 account for ? Type 2 ?

A

10% Type 1

90% Type 2

34
Q

How is Type 1 Diabetes treated ?

A

By injecting insulin when required

35
Q

How is Type 2 Diabetes treated ?

A

Managed by exercise and losing weight

36
Q

What are the main feature of type 2 diabetes ?

A
  • Lifestyle-associated (little exercise, ready access to food and obesity)
  • Possible genetic component
  • Tissues insensitive to the effects of insulin
  • Glucose cannot be taken up by cells and so remains in the blood
37
Q

How would a diabetic person compare with a non-diabetic person in terms of blood glucose following ingestion of glucose ?

A

The rise in blood level is higher and longer than in a non-diabetic individual


38
Q

What other units may be used instead of mg %, when talking about blood glucose ?

A

1 mg %
= 1 mg/100 ml
= 1 mg/dL

39
Q

Is there any difference in glucagon levels in the blood in diabetes ?

A

Increased glucagon levels

40
Q

How does metabolism change in diabetes ?

A

Because tissues are not influenced by insulin, metabolism is largely similar to that seen during prolonged fasting:

  1. Glycolysis is slowed
  2. Gluconeogenesis (new glucose) is stimulated (using amino acids produced by protein breakdown)
  3. Fatty acids (from adipose tissue) are broken down and used to form ketone bodies
  4. Newly formed glucose and ketone bodies pass into the blood
41
Q

Why is untreated diabetes associated with excessive urination, and increased concentration of glucose and ketone ?

A
  1. In the glomeruli of the kidney glucose leaves the blood and passes into the urine along with ions and other relatively small molecules
  2. Normally transporters in the proximal convoluted tubule reabsorb all the glucose and return it to the blood
  3. In diabetes if the blood [glucose] rises beyond a certain level, the amount that passes into the kidney tubules is so great that the transporters cannot remove it all
  4. This glucose adds to the osmotic strength of the urine
  5. This makes it harder for the kidney to reabsorb water from the urine
  6. The result is that the urine volume is greatly increased
    - It also explains why the urine of a diabetic contains glucose
  7. In severe cases, acidic ketone bodies also appear in the urine (ketoacidosis) adding slightly to the osmotic strength (explains why the urine of a diabetic contains ketones)
42
Q

What are examples of tissue damage diabetes can result in, in the long term ?

A
  • Blood vessels (polyneuropathy)
  • Eyes (Retinal blood vessels)
  • Kidneys (urine infection; scarring and swelling in glomeruli leading to appearance of protein in the urine)
  • Cardiovascular disease (largely a result of narrowing of blood vessels)
43
Q

What is a possible pathological consequence of ketone bodies accumulation ?

A

Acidosis –> possible coma due to low blood pH, coupled with dehydration

44
Q

Can acidosis as a result of ketone bodies accumulation be fully counteracted ?

A

No

MD2002 Lucas (111 decks)

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