Describe the enzymes required for the digestion of carbohydrates and their location.
- Salivary Amylase
- Duodenum – Pancreatic Amylase
- Brush Border Oligosaccharidases
- Examples of these oligosaccharidases are:
- alpha-dextrinase (isomaltase)
- lactase, sucrase, maltase & trehalase
- Final oligosaccharides:
- alpha-dextrins, maltotriose, maltose, trehalose, lactose, sucrose are metabolized to one of the hexoses (monosaccharides-galactose, fructose or glucose)
- Bold to pass
Please describe how carbohydrates are absorbed from the gastrointestinal tract.
- Two phases: first into intestinal mucosal cell and second into interstitial fluid (ECF) and thus into capillaries & portal blood
- Glucose/Galactose “secondary active transport” with sodium – low concentration of Na inhibits transport (co-transporters: SGLT-1 & SGLT-2 – sodium-dependent glucose transporter)
- Glucose/Galactose – “facilitated diffusion” into ICF by GLUT-2
- Fructose – “facilitated diffusion” from intestinal lumen by GLUT-5, thence GLUT-2 into ICF
- Ribose/Deoxyribose Diffusion
Describe the enzymes required for the digestion of proteins and their location.
- Stomach – pepsinogens activated by gastric hydrochloric acid (pH 1.6-3.2) to pepsins result in polypeptides
- Small intestine lumen (pH 6.5) – proteolytic enzymes of the pancreas & intestinal mucosa
- Examples: endopeptidases (trypsin, chymotrypsin & elastase) & exopeptidases to amino acids
- Brush border: (amino, carboxy, endo & di) peptidases to amino acids
- Cytoplasm of mucosal cells: after absorption by active transport
- 3 out of 5 to pass
Describe how proteins are absorbed from the gastrointestinal tract.
- Two phases: first into intestinal mucosal cell and second into interstitial fluid (ICF) and thus into capillaries & portal blood
- Into enterocytes: seven different transport systems for amino acids (sodium dependent and independent)
- Out of enterocytes: five different transport systems
- 2 out of 3 to pass
Describe the enzymes required for the digestion of lipids and their location.
- Lingual lipase (Ebner’s Gland) – active in the stomach on triglycerides
- Pancreatic lipase – requires colipase for maximal activity (triglycerides)
- Pancreatic bile-salt activated lipase (not only triglycerides but also cholesterol esters, some vitamins & phospholipids)
- Cholesteryl ester hydrolase (cholesterol)
- 2 out of 4 to pass
What other process is involved in the digestion of lipids?
- Micelles – formed from bile salts, lecithin and monoglycerides surrounding fatty acids, monoglycerides & cholesterol
- Transport lipids thru “unstirred layer” to brush border of mucosal cells
Please describe how lipids are absorbed from the gastrointestinal tract.
- Two phases: first into intestinal mucosal cell and second into interstitial fluid (ECF) and thus into capillaries & portal blood (FFA – free fatty acids) or into lymphatics (chylomicrons)
- Into enterocytes: passive diffusion & carriers
- Out of enterocytes: depending on size (< 10-12 carbons – directly into portal blood (FFA’s) OR > 10-12 carbons – reesterified to triglycerides or cholesteryl esters & packaged in chylomicrons (coating of protein, cholesterol & phospholipids)
Describe the characteristics of nerve fibers responsible for transmission of 'fast pain'?
- Myelinated A delta fibers
- 2-5 um diameter
- Conduction rates 12-30 m/s
- End in dorsal horn (lamina 1 and 5)
- Neurotransmitter is glutamate
- Pass = myelinated PLUS 2 out of 4
What differences are there between these nerve fibers and those responsible for transmission of “slow” or second pain?
- unmyelinated C fibers
- smaller 0.4 – 1.2 um diameter
- Also dorsal horn but lamina 1 and 2
- Neurotransmitter is substance P
- Different sensation – dull / intense / diffuse
- Different locations as less A delta fibers in deeper structures
- Bold PLUS 1 other
What do you understand by the term referred pain?
- Same embryonic segment or dermatome
What are the major factors determining the plasma glucose level?
- Concept: Balance between glucose entering the bloodstream and glucose leaving the bloodstream.
- Dietary intake
- Cellular uptake (partic muscle/fat/ hepatic)
- Hepatic glucostat / glycogenisis, glycogenolysis, gluconeogenisis
- Renal freely filtered but PT reabsorbed to Tmax
- Hormonal effects on these (particularly 1, 3,4)
List the hormones which effect plasma glucose levels?
- Decreased BSL – Insulin (),Ins like GF 1and 2- (NSILA)
- Insulin via glucose uptake (al tissues), glycogenogenesis, Liver -gluc to fat, – IGF- similar but much
- Increased BSL Catecholamines (Nor / Epi partic) (>),Glucagon (>), GH>, Cortisol>, Thyroid
- Catechol –b receptor > cAMP- glycogenolysis/ gluconeogenesis
- Glucagon- cAMP direct- as catecholamines
- TFTs- > absorption + increased glycogenolysiss (liver partic) + ins bkdown increased
- Cortisol- permissive to Glucagon/Catechols + some glucgenesis, prot to gluc liver- < uptake
- GH- > gluc liver, insulin block, <tissue uptake
- 3 hormones + correct
What are the principal functions of the Liver?
- Bile formation (500 mls a day) – Excretion, elimination, digestion
- Synthesis– protein/ coag/ biding prot/alb
- Inactivation/ detox –drugs/toxins/ active circ substances
- Nutrient vitamin absorption, metabolism/ control (e.g. glucostat) AAs, lipids, fat sol vits etc
- Immunity (partic gut orgs)- Kupffer/ Macrophages in sinusoid endothelium
- 3/5 named functions
Describe bilirubins path from production to excretion.
- Most formed by breakdown of Heme /Hb.
- Bilirubin bound to albumin *
- In liver actively transported (OATP) as dissociates –binds to cytoplasmic proteins.
- Conjugated by gluc-transferase (*in ER) with glucoronic acid to H20 sol bil-digluc
- Bil di gluc active transport (MDRP2) against gdt to bile canaliculi – to gut. (<5% bil/bdg reflux to blood)
- Intestinal mucosae relatively impermeable
- Gut bacteria act / convert most to urobilinogens*
- Some bile pigments/ urobilinogens/unconj bil reabsorbed in portal circn –most resecreted– entero hepatic circulation.
- Small amounts urobil in blood excreted in urine – urobilinogen and faeces – stercobil
- 4 elements in proper order/ prompt if stuck on excessive detail e.g. just a general overview of production to excretion. Pass does not require this detail!
What factors control blood glucose levels?
- Dietary intake
- Rate of entry into cells
- Glucostatic activity of the liver (storage of glycogen, breakdown of glycogen, gluconeogenesis)
What are the potential pathways for glucose metabolism in the body?
Physiologically what are the acute consequences of insulin deficiency.
- Intracellular glucose deficiency; extracellular excess; protein and fat catabolism
Describe the biosynthesis of insulin.
- B cells as a precursor hormone; insulin released rom the cell with C peptide.
Describe the structure of the insulin receptor.
- 2 alpha and 2 beta glvconrotein subunits.
Name the principal pancreatic enzymes and the substances upon which they act.
- Trypsin — proteins, polypeptides
- Chymotrypsin — proteins, polypeptides
- Elastase — elastin and some other proteins
- Carboxypeptidase A & B — proteins, polypeptides
- Colipase — fat droplets
- Pancreatic lipase — triglycerides
- Bile salt-acid lipase — cholesterol esters
- Pancreatic a-amylase — starch
- Ribonuclease — RNA
- Deoxyribonuclease — DNA
- Phospholipase A2 — Phospholipids
Pass: Must be able to give trypsin, lipase, amylase plus 1 other & their appropriate substrate group (protein, fat, carbohydrate)
Describe the regulation of pancreatic juice secretion.
Prompt: Do you know any hormones involved in secretion of pancreatic juice?
- Primarily under hormonal control
- Secretin acts on the duct to cause production of copious amounts of very alkaline pancreatic juice poor in enzymes.
- As flow of pancreatic juice increases it becomes more alkaline because exchange of HCO3 for Cl in the dista duct is inversely proportional to flow
- CCK acts on acinar cells to cause of release of zymogen granules and pancreatic juice rich in enzymes
- Acetylcholine also stimulates release of zymogen granules (minor effect basis of vagally-mediated pancreatic juice secretion in response to sight/smell of food).
Pass: Must give Secretin and CCK and know that secretin causes mainly alkaline fluid and CCK mainly enzymes.
Describe the metabolism of bilirubin.
Breakdown of haemoglobin leads to bilirubin which is bound to albumin in the circulation. In the liver it dissociates and free bilirubin enters the hepatic cell where it is conjugated by glucuronyl transferase with 2 molecules of uridine diphosphoglucuronic acid (UDPGA) to form bilirubin diglucuronide and UDP. The diglucuronide is more water soluble than free bilirubin.
Pass: Must be able to identify metabolism in the liver by glucuronidisation to a more soluble form which is then mostly excreted via bile.
How is bilirubin excreted?
It is mostly passed into the bile ducts and excreted via the intestines. A small amount enters the blood and is measurable as conjugated bilirubin in the blood.
What factors regulate gastric secretion?
Neural and hormonal OR
Cephalic, Gastric and intestinal
Cephalic; food in mouth -> vagus,
psychologic states eg anger hostility -> hypersecretion
Gastric: food in stomach, local receptors eg to amino acid and protein digestions -> post ganglionic neurons -> parietal cells -> acid secretion
Intestinal: fats, carbohydrates, and acid in duodenum inhibit gastric acid secretion and pepsin secretion as well as motility by neural and hormonal mechanisms Eg peptide YY
Neural: Vagal increases gastrin secretion in G cells by GRP. Gastrin stimulates gastric acid and pepsin secretion as well as motility.
Hypoglycaemia via vagus to stimulate acid and pepsin secretion
Also alcohol and caffeine stimulate gastric secretion
Pass: Need to name both and give an example of each (vagus, hormonal eg: gastrin)
Describe the composition of pancreatic juice.
Composition: cations, anions, HCO3-, Digestive enzymes — Proenzyme trypsinogen converted to trypsin by enteropeptidase (enterokinase) from brush border. Trypsin converts chymotrypsinogens, proelastase, procarboxypeptidases to active enzymes. Digestive enzymes in zymogen granules in acinar cells in alveolar glands, discharged by exocytosis into pancreatic ducts.
Describe the regulation of secretion of pancreatic juice.
Secretin — HCO3-, 1500m1/day; bile secretion. CCK — releases zymogen granules (also vagal acetylcholine)
List the principal functions of the liver.
- Bile formation (500mL/day)
- Synthesis – protein, coagulation factors, albumin
- Inactivation/detoxicification – drugs, toxins, active circulating substances
- Nutrient vitamin absorption, metabolism/control (e.g. glucostat), amino acids, lipids, fat soluble vitamins
- Immunity (especially gut organisms) – Kupffer/macrophages in sinusoid endothelium
- 3/5 bold + example to pass
Describe the metabolism of bilirubin.
- Formed by breakdown of haeme, Hb
- Bound to albumin
- In liver – actively transported (OATP) as dissociates – binds to cytoplasmic proteins
- Conjugated by gluc-transferase in endoplasmic reticulum with glucuronic acid to H2O sol bi-digluc
- Bil di gluc active transport (MDRP2) against gdt to bile cnaaliculi – to gut (<5% bil/bdg reflux to blood)
- Intestinal mucosa relatively impermeable
- Gut bacteria act/convert most to urobilinogens
- Some bile pigments/urobilinogens/unconjugated bilirubin reabsorbed in portal circulation – most resecreted = enterohepatic circulation
- Small amoutns urobilinogen in blood excreted in urine – urobilinogen and faeces – stercobil
- Bold to pass