DMG PBL Conditions Flashcards
How is pain generated in heartburn?
How is heartburn distinguished from oesophagitis?
How are TLOSR and GORD related?
Afferent nerves in oesophageal wall activated by luminal acid/other gastric components -> generates signal by spinal and (less so) vagal fibres to CNS
Oesophagitis: inflammation of oesophageal mucosa caused by reflux of stomach content damaging mucosa. Heartburn: phenotype when acid refluxes to oesophagus.
Increased TLOSR can lead to GORD
What is the mechanism of alginates in treating GORD?
Name 3 anatomical features that prevent reflux
Form floating raft which separates gastric contents from the gastro-oesophageal junction to prevent mucosal damage. Decreases reflux.
- Angle of His: acute angle between cardia and oesophagus, creates valve that acts as functional sphincter
- Viable LOS: region of higher pressure closes lumen
- Presence of terminal portion of oesophagus in abdominal cavity under diaphragm - helps keep sphincter closed
- The walls of the intra-abdominal section of the oesophagus are compressed when there is a positive intra-abdominal pressure
- The folds of mucosa present aid in occluding the lumen at the gastro-oesophageal junction
What are the muscularis propria layers in the stomach in order from inner to outer?
What is the mechanism behind increase in stomach acid secretion?
What receptors (and the things that bind to them) are found on the parietal cell and affect acid secretion?
Inner oblique, Circular, longitudinal
Under parietal cell apical membrane there are primed vesicles containing H+/K+ ATPase, these are translocated to the membrane of the parietal cell to increase acid secretion.
H2 (histamine), CCKB (gastrin), M3 (ACh), SST2 (somatostatin - inhibitory, from D cells)
What is the alkaline tide?
What is the inflammatory response to H. pylori colonising near the pyloric antrum?
Maintains body alkalinity: after eating a meal, where during the production of HCl by parietal cells in the stomach, the parietal cells secrete bicarbonate ions across their basolateral membranes and into the blood, causing a temporary increase in pH.
Produces urease which breaks down urea in stomach to CO2 and NH3. NH3 is toxic to D cells -> lower level of somatostatin (which usually inhibits acidity of stomach) -> ulceration and poss cancer when lots of acid.
Which vitamin, present in the composition of Prabinex, is given to prevent a specific type of encephalopathy? Considered irreversible, what is the name of this syndrome?
Give 2 reasons why lactulose is an important treatment for liver failure?
Thyamine (B1), Wernicke’s encephalopathy
NH3 -> NH4 = decreases hepatic encephalopathy risk. Decreases ascites by helping remove fluid from gut contents
List the 8 functions of the liver
GBP SALAD
1) Glucose metabolism
2) Bile production
3) Plasma protein synthesis (clotting factors, albumin, CRP, alpha1-antitrypsin…)
4) Storage (vitamins A, D B12, Fe etc.)
5) Amino acid metabolism -> urea cycle
6) Lipid metabolism (prod chol, bile etc.)
7) Alcohol metabolism
8) Detoxification (add OH, make lipid soluble, excrete)
What are the following involved with:
a) B1 thiamine
b) B2 riboflavin
c) B6 pyridoxal 5’-phosphate
d) Vit c ascorbic acid
a) cofactor for several enzymes, particularly thiamine pyrophosphate (cofactor for pyruvate dehydrogenase complex). Deficiency = Wernicke-Korsakoff syndrome.
b) main active form is FAD. Also forms FMN in complex I whcih helps move e- between F:S clusters to reduce UQ
c) cofactor for several enzymes e.g. glycogen phosphorylase
d) cofactor in collagen synthesis, protects against ROS as an antioxidant, required to make carnitine for FA transport into mitochondria for beta oxidation
State 4 metabolic fuels used by exercising skeletal muscle to provie the ATP necessary for contraction.
Why does the exercising muscle send lactate to the liver for GNG rather than pyruvate?
Explain why athletes increase consumption of pasta and B group vitamins shortly beefore a race.
Glucose, glycogen, FA, AA, PCr, Ketones, Triglycerides
Regenerate NAD+
Pasta: top up liver glycogen
B vitamins: B1 in TPP (thiamine), B2 riboflavin = FAD precursor, B3 niacin = NAD precursor
Briefly outline the mechanism whereby hypoxia brings about appropriate adaptation to enhance energy metabolism in skeletal muscle.
i) specifically what transcription factor is involved?
ii) how does hypoxia affect its function?
iii) what are the downstream metabolic adaptations within the cells?
i) HIF-1 (hypoxia-inducible factor)
ii) Hypoxia: HIF1 activity enhanced by stabilisation of its alpha subunit. Active HIF1 binds to hypoxia-response elements (HREs) in the promoter regions of ‘metabolic’ genes (e.g. for glycolytic enzymes, VEGF, EPO)
iii) The effect is to up-regulate glycolysis and to suppress mitochondrial activity
How do the levels of insulin and glucagon affect the main pathways of glucose metabolism in someone diabetic in hyperglcaemia?
What is the effect of lack of insulin on lipid metabolism? How does it contribute to ketogenesis?
What is the effect of alcohol on the NAD/NADH ratio in the liver? How does this affect glucose metabolism?
No insulin, so produces glucagon. Promotes glycogenolysis (inhibits glycogenesis), promotes GNG, inhibits glycolysis in liver, induces lipolysis (-> ketone bodies)
No insulin stimualtes lipolysis -> liver frees up FA, which can be used for ketogenesis (normally insulin inhibits HSL)
NADH increases. Inhibits TCA, drives to producing lactate, blocks glycolysis, blocks GNG (b/c inhibits malate dehydrogenase)
Breifly explain the mechanism that normally prevents appearance of glucose in the urine and how is it affected in patients with type 1 diabetes?
Could ketoacids be part of the unmeasured cations or anions? What other acids could also be unmeasured anions?
Glucose filtered and reabsorbed from PCT (most), DCT and CD, normally via basolateral K+ Na+ pump. Type 1: so much glucose that saturates the transporters = glucose not reabsorbed and passes out in urine.
Unmeasured anions. Lactic acid.
What chemical process is measured by HbA1c level? What does HbA1c reflect?
State the mode of action of the drugs Metformin and sitaglitpin. How are they used in management of T2D?
Glycated Hb - A1c cahin of Hb is glycated, reflects BG control over past 2-3m, reflection of poor BG control if increase
Metformin: decreases appetite by controlling leptin secretion. Increases sensitvity to insulin and inhibits hepatic GNG
Sitaglitpin: DPP-4 inhibitor so GLP-1 remains = increases insulin secreation from pancreas
What tissue is the source of a) leptin b) GLP-1? What changes cause an increaese in each of these hormones?
What is a BMI of 28 classed as?
What is a more accurate measurement than BMI and why?
Name 4 hormones triggering satiety.
a) Leptin - adipose tissue, increases if lots of fat in cells
b) L cells of small intestine - inhibits NPY and stimulates POMC, increase if satiated
Overweight
Waist:hip - better correlation with T2D
CCK, Leptin, PYY3, GLP-1, 5-HT, insulin
What are the 2 full names of the hormones secreted by the cuboidal cells of the thyroid gland follicles?
Name 2 consequences of hyperthyroidism on glucose metabolism.
Why is the thyroid gland enlarged in Hashimoto’s thyroiditis, and why is TSH elevated?
thyroxine (T4), triiodothyronine (T3)
Leads to insulin resistance mainly associated with an increase in hepatic GNG
Activation of autoantibodies -> inflammation and increase in size. TSh increase b/c low T3 and T4 which would normally -vely feedback and inhibit futher pituitary TSH release
Name 2 metabolic changes triggered by thyroid hormones at the cellular level.
What treatment would you give for someone with Hashimoto’s thyroiditis?
Change in ATP synthesis via oxidative phosphorylation in mitochondira. Increase in mitrochondria genesis.
HRT for T4 - levothyroxine. Normally start at low dose and gradually increase to reverse SEs of hypo wihtout causing adverse effects esp. cardiac.
