Metabolism Flashcards
What does sweet smelling breath indicate?
Ketones
What are the two cycles of gluconeogenesis and what hormone stimulates these?
Cori cycle - lactate to pyruvate
Alanine cycle - alanine to pyruvate
All done by glucagon
How do muscles breakdown glycogen compared to the liver?
The muscles cannot impact glucose homeostasis in the blood, their glycogen is therefore not turned into glucose but turned only into Glucose-6-phosphate (G6P) to go straight into the Krebs cycle.
Why does blood become acidic in T1D?
Ketones are acidic
Why might T1D cause an AKI?
Glucose in the urine will cause water to follow, leading to hypovolemia and AKI.
Why is insulin a dangerous medicine?
it is essentially limitless, it can easily cause hypoglyceamia. Need to treat with food or glucagon.
What are the 3 P’s of diabetes?
Polyuria, Polydypsia, Polyphagia
Which molecule makes you hungry?
Ghrelin
What tissues make lectin, what does it do?
Lectin is made by adipocytes, it sends satiety signals.
What does a displaced apex beat indicate?
LV hypertrophy
What is the goal HbA1c of diabetes?
Under 7
What is key to treating diabetes aside from direct anti-diabetic drugs?
Treating risk factors - lipids, HTN etc.
Describe the steps in glucose mediated insulin release
Glucose enters cell via insulin independant GLUT channel
Membrane depolarisation
Calcium influx
Pre-made insulin granule release
Describe the action of insulin
Insulin binds to receptors on cells and causes trans-autophosphoylation of molecules like IRS, which eventually causes movement of pre-made GLUT4 molecules to the cell surface to take in more glucose.
What is the earliest factor of T2D?
Insulin resistance
How does obesity lead to insulin resistance?
It’s all IRS - obesity causes serine phosphorylation of IRS instead of desired tyrosine. Inflammation due to adiposity fucks with IRS. Excess fats fuck with IRS. Enlarged adipocytes fuck with IRS.
What are the stages of type 2 Diabetes?
- Hyper insulin, normal blood glucose
- Hyper insulin, high blood glucose
- Low insulin, high blood glucose
What are the microvascular and macrovascular long term impacts of T2D?
Micro: Eyes, Kidneys, Nerves
Macro: Stroke, HTN, Vascular disease
Where are GLUT 2, 3, and 4 and how active are they?
GLUT 2 - Liver - only at high glucose
GLUT 3 - Brain- always active
GLUT 4 - virtually everywhere, active under insulin.
What are the enzymes that make and break glycogen?
make - glycogen synthase
break - glycogen phosphorylase
Which ‘shuttles’ are needed to recycle NAD in aerobic respiration?
glycerol and malate pathways
How does metformin work?
It inhibits the glycerol shuttle of the Cori Cycle, preventing gluconeogenesis in the liver.
Increases glucose sensitivity elsewhere.
What impact does cortisol have on blood sugar?
It raises it by causing gluconeogenesis.
What causes the microvascular impacts of T2D?
Hyaline arteriosclerosis, likely due to glycated end products of diabetes.
What does diabetes do to the kidneys?
SCARRING
Glomerulosclerosis, tubular sclerosis, arteriosclerosis.
Exercise builds what type of adipose tissue?
Beige. Want to avoid white.
What is the double burden of malnutrition?
Obesity alongside nutrient deficiencies
List the drug classes for T2D? How do each work?
Sulphonylureas - inhibit K+ ATP channels - force the membrane depolarisation causing insulin release. (Mimic insulin independant path)
Biguanides (Metformin) - reduce liver gluconeogenesis, increase peripheral insulin sensitivity, reduce LDLs.
Incretin mimetics - newer, modulate insulin.
Glucose reabsorption modulator (glifozins) - fuck with sodium/glucose transporter in kidney (SGLT).
Glucose absorption modulators - impedes absorption of starches in gut
List the classes of obesity drugs? How does each work?
Phentermine - amphetamine - increases NA - reduce appetite.
Topirimate - for epilepsy and migraines - mechanism unknown, weird tastes common.
Orlistat (orlishat) - inhibits gastric and pancreatic liapses - only one that doesn’t cause suppressed appetite.
Liraglutide - GLP1 receptor agonist - great for weight loss and T2D !!!
Side effect of orlistat?
Shit yourself, fatty stools, ADEK deficiency.
Who is contraindicated for phentermine?
CVD and SSRI users
How do Type III hypersensitivities progress?
IgG or IgM with antigen form complexes but are not big enough to be picked up by C3b yet so they move around the body and build up until C3b picks them up and causes inflam.
Why do people with allergic reactions need to be watched carefully for 24 hrs after an attack?
Late phase reaction due to non-histamine molecules like PGE, leukotrienes etc.
What are the findings of a agglutination assay using streptolysin?
If someone has had strep, they will have antibodies to streptolysin. So their blood will inactivate streptolysin, causing the blood to form in a button in the well. If the well is all red, streptolysin is working and not inhibited therefore the person has no Ig.
What type of hypersensitivity is Rheumatic fever/heart disease?
Type 2 - cytotoxic
Which two antibody types are made in coeliac and how can we get these two from the one T cell reaction?
Tissue transglutaminase IgA and deaminated gliadin IgG.
Done by epitope spreading - a T cell will activate all of the epitopes targeted by a B cell not just the one used to interact with the T cell itself.
I.e - if the B cell takes in 3 antigens and only 1 is a peptide, sharing the 1 peptide one with the T cell and getting its help will lead to proliferation of antibodies against all 3 antigens, not just the peptide.
What organism are picked up on a DCA plate and what colour are they?
Black = salmonella
beige = shigella
Describe the hookworm life cycle.
Chew up foot
Chew into lungs
Swallowed
Eggs in feces
Describe the Ascaris lifecycle and their eggs
Ascaris (roundworm) eggs sort of have bumps all over.
Egg in feces.
EGG EATEN - makes it different.
larvae hatch in jujunum, travel to lungs.
Coughed up.
GIT - eggs in feces.
Describe the strongyloides lifecycle.
worm burrows into feet.
chews to lungs.
cough up into GIT.
EGGS HATCH IN GIT - different.
larvae exit in stool but can easily cause autoinfection.–. SEPSIS due to worms bringing gut bacteria with them.
Where can S. typhi hide forever in the body?
Gall bladder
What will be the first test to pickup salmonella typhi infecrtion?
Blood test
What are the two cycles of the malaria lifecycle in the human?
Liver cycle then erythrocytic cycle.
P. vivax can shed for a year.
How does diabetes lead to nephropathy?
- chronic hyperglycaemia
- glycation of tissues
- glycation and thickening of basement membrane
- glomerular hypertrophy
- glomerulosclerosis
- low GFR
-glifozin drugs act in what way and what side effect can they cause?
SGLT2 inhibitors - will lead to lots of glucose in the urine which can cause infections and frequency.
Which weight loss drug should not be taken with opiods?
Contrave
What are the 5 components of metabolic syndrome?
low HDL, HTN, central adiposity, high triglycerides, high glucose
How does Liraglutide work?
It is a GLP-1 agonist - GLP acts on incretin receptors to force insulin production.
What GLUT do cancers upregulate?
GLUT1
