Clinical Biochemistry Flashcards
What does insulin stimulate?
- Glucose uptake in muscle and adipose tissue
- Glycolysis
- Glycogen synthesis
- protein synthesis
- uptake of ions (especially K+ and PO43-)
What does insulin inhibit?
- Glucogenesis
- Glyconeogenesis
- Lipolysis
- Ketogenesis
- Proteolysis
What does reduced cellular uptake of glucose result in?
Hyperglycaemia
What does hyperglycaemia cause?
Excess glucose spills into urine
- glycosuria
- osmotic diureses
What results from dehydration?
Hypotension and shock
What happens if the body is resistant to insulin or deficient?
Body tries to source insulin from other fuels
-triglycerides
What are ketones?
Intermediates of fat breakdown- strongly acidic, dissociate and release protons
What do ketones cause?
Vomitting
What does hypotension and shock cause?
Stimulate release of hormones which exacerbate the process (anti-insulin) >AVP >Growth hormone >Cortisol >Catecholamine
What is lipolysis?
Breakdown of lipids
What is the role of hormone sensitive lipase?
> Releases free fatty acids and glycerol
>occurs when energy is needed
Where are ketone bodies formed?
Liver mitochondria
Where do ketone bodies diffuse to?
Blood stream and peripheral tissues
What is ketone body acid load?
Highly acidic ketone bodies release hydrogen ions into the blood
What happens to bicarbonate buffering in blood during keto-acidosis?
excess hydrogen ions mop up most of the available bicarbonate ions
Because carbon dioxide is blown off the reaction never reaches equilibrium
What is kussmaul breathing?
Deep sighing respiration
acidotic breathing
How can DKA be identifies?
Ketones= dipstick
DKA can be smelt from across the room
Air hunger
Why can some people mobilise glycogen stores?
Lack of enzyme
- Phosphorylase
- Transferase
- a-1,6-glucosidase
What is the problem with lactate?
Yields much less energy than oxidative metabolism
What is the long term consequence of not being able to bread down glycogen?
Accumulates;
- hepatomegaly, portal hypertension
- fibrosis of the liver
What are the clinical features of not being able to break-down glycogen?
Hypoglycaemia in early llife
Hepatomegaly
Heart can be affected- heart failure, lung failure, death
What are the main components of the plasma membrane?
Phospholipid
Sphingomyelin
Cholesterol
What does cholesterol do in the membrane?
Maintain structure and fluidity of cell membrane
What is cholesterols role in cell singnalling?
Form lipid ‘rafts’ that form bridges between receptor proteins and second messengers
-lipid rafts are parts of membrane that serve as centres for assembly of signalling molecules
What is cholesterol a precursor of?
Bile/bile acids (important in digestion and absorption of fat soluble vitamins), vitamin D and steroid hormones
What is the function of triglycerides in health?
Similar to cholesterol in membranes- polar and non polar
Highly concentrated energy stores
How are lipids carries around the body?
Lipoproteins in the blood
How do lipoproteins vary?
Physical properties vary according to the specific composition of their lipids
Describe lipoproteins from the liver?
Comparatively triglyceride rich, progressively lose TG content as they travel through the blood
How is triglyceride removed from lipoproteins?
Lipoprotein lipase snips off as they travel through the blood (lines blood vessels)
What is the densest lipoprotein and its function?
HDL
Carries cholesterol from the tissues to the liver
What is the formation of lesions mediate by?
Oxidised LDL
What is cholesterol transport from liver to tissues controlled by?
Bouyant lipoproteins like VLDL which after progressive dilapidation become denser IDL, LDL)
What is cholesterol transport from tissues to liver mediated by?
Principally by HDL
What happens when LDL is not effectively cleared?
Accumulates, gets chemically modified (oxidised) and aggregates. This acts as a trigger for macrophages- mediate inflammation and swallow stuff
What does inflammation do to cholesterol transport?
Inhibits reverse cholesterol transport, exacerbating the imbalance and a feedforward or vicious circle of increasing LDL and increasing inflammation
What is a case-control study?
two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute
What is a cohort study?
follows a group of people over time, e.g. with reference to risk factors for a disease
What is a systematic review?
literature review focused on a research question; tries to synthesize all relevant high-quality evidence
What is meta-analysis?
Statistical technique for combining findings from independent studies
What is a randomised clinical trial?
experiment in which trial participants are randomly allocated to treatment under study.
What do statins do?
Lower cholesterol.
Interfere with cholesterol synthesis in the liver cell, which then expresses more LDL receptors in an attempt to get more cholesterol into the cell
What do statins inhibit?
Smooth muscle migration
Foam cell formation
T-cell activation
Adherence and aggregation of platelets
Adherence and entry of leukotrienes
