Biochemistry: Application 1+2 Flashcards
what does insulin signal and pathways does it switch on
fed state and metabolic pathways involved in using or laying down ingested fuels
what does insulin stop (5)
- proteolysis
- glucogenesis
- glycgenolysis
- lipolysis
- ketogenesis
what does insulin start (5)
- glucose uptake in muscle and adipose tissue
- glycolysis
- glycogen synthesis
- protein synthesis
- ion uptake
what pathways does insulin switch off
those involved in mobilising fuel stores
describe the consequences of decreased cellular glucose uptake in an insulin-deficient/resistant patient
leads to hyperglycaemia (glucose not used) -> glycosuria -> osmotic diuresis (lots of peeing lots of glucose) -> dehydration -> hypotension and shock
describe the consequences of increased lipolysis in an insulin-deficient/resistant patient
this is an attempt to source glucose leading to
increased ketones in blood -> acidosis -> vomiting -> dehydration -> hypotension and shock
what is the result of hypotension and shock from insulin deficiency/resistance
anti-insulin factors are released exacerbating the cycle
anti-insulin factors
- cortisol
- growth hormone
- AVP
- catecholamine
what is the main reason for insuline resistance and why
- obesity
- too much fuel is stored as fat so the body becomes resistant to laying down more
role of hormone sensitive lipase in lipolysis and when this occurs
- releases free fatty acids and glycerol
- when energy is needed
where are ketone bodies formed
liver mitochondria
what happens to the bicarbonate equilibrium when there is excess ketones in the blood
a R shift due to excess H+ being mopped up by H2CO3
why is the bicarbonate equilibrium never reached in a right shift
CO2 is blown off and therefore backwards reaction cant occur
what is acidotic breathing
deep breathing
can dipsticks detect ketones in urine
no
what are the fates of glucose on the liver
- glycogen stores
- triglyceride stores
when are glycogen and triglyceride stores used
when quick energy is needed - sprinting
what other sources can glucose be made from
- amino acids
- glycerol
- lactate
what is glycogenolysis
breakdown of glycogen to form glucose
what is gluconeogenesis
synthesis of glucose from alternate sources
what IC enzymes appear in plasma due to normal cell turnover (MSK and Liver)
- MSK - CK and AST
- liver - ALT, AST. ALK Phos, Gamma GT
what what IC enzymes appear in plasma due to tissue damage (blood, bone, heart, pancreas)
- blood - AST and LDH
- heart - AST, CK, troponin, LDH
- bone - ALK Phos
- pancreas - amylase, lipase
what IC enzymes are good diagnostic indicators
heart, blood, bone, pancreas, MSK, liver
- heart - troponin
- blood - LDH and AST
- bone - ALK Phos
- pancreas - amylase
- liver - ALK Phos, ALT, Gamma GT
- MSK - CK
how is lactate recycled to glucose when body is stuck for energy and where
lactate -> pyruvate -> glucose (+6-P)
- liver
cholesterol role in:
- cell membrane
- cell signalling
- helps maintain fluidity and structure
- forms lipid rafts between receptors and secondary messengers
what is cholesterol a precursor for (3)
bile/bile acids, vit D and fat-soluble hormones
what type of storage are triglycerides
high conc. energy store
role if triglycerides in cell membrane
similar to cholesterol, structure and fluidity
what carries lipids around the body
lipoproteins
what is the triglyceride composition of lipoproteins leaving the liver and what happens as they travel around the body
TG rich, progressively lose TGs as they circulate and become more dense
what enzymes snips off triglycerides in the endothelium of blood vessels
lipoprotein lipase
role of HDL
carries TG from tissues to liver
earliest changes of atherosclerosis in blood vessels
- increased endothelium permeability to lipoproteins and plasma consituents
- upregulation of WBCs and endothelium adhesion molecules
- WBC migration
what mediates atheroscleorsis formation
oxidised LDL
earliest visible signs of atherosclerosis
later joined by what
fatty streaks, SM cells
describe the process of atherosclerosis formation
- SM cell migration
- T-cell activation
- foam cell formation
- platelet aggregation and adherence
what are foam cells
macrophages laden with lipids
when is a fibrous cap formed
when the fatty streaks progress to intermediate and advanced lesions
what do fibrotic caps do and what do they form as a result of
cap off the lesion in a healing/fibrous response to injury
what do fibrous caps cover
WBCs, lipids, debris
what forms a necrotic core in a fibrous caps
debris
why do necrotic cores form in fibrous caps
result of apoptosis, necrosis, increased proteolytic activit and lipid accumulation
how do atherosclerotic lesions expand at the edges
continues WBC adhesion and entry
how do thrombus form and where does this usually occur
- rupture or ulceration of fibrotic plaques
- sites of fibrous cap thinning
how do fibrotic caps thin
result of continues influx and activation of macrophages that release proteolytic enzymes degrading the matrix
what do labs measure in terms of cholesterol and why
- cholesterol, total cholesterol, HDL, total HDL, triglycerides
- estimate CV risks
what is the lipid hypothesis
decreased cholesterol and saturated fats, decreases atherosclerosis and risk of CV disease
case-control study
two groups with a different outcome identified and compared on a basis of a suspected casual factors
cohort study
follow a group of people over time with reference to disease risk factors
systematic review
lit review focused on a research question - high quality evidence
meta-analysis
stat technique for combining results of different studies
randomised clinical trial
experiment where trial pateints are randomly assigned treatment under study
statin MoA
inhibit cholesterol formation from acetate in the liver
how do lipoproteins become acetate
via liver LDL receptors
whilst lowering cholesterol what else do statins do
inibit processes involving cholesterol and inflammation i.e. SM migration, T cell activation
what happens to atherosclerotic plaques as a result of statins
- dont form as much
- existing ones become more stable
