GI - Nutrition and Digestion Flashcards

Question

What tissues/structure within and surrounding the liver provide support?

Answer 1

Enclosed by a thin Collagen Tissue capsule - provides liver support Liver is mostly covered by the mesothelium - epithelial cells covering the liver surface Collagen tissue of the branching vascular system within the liver provides gross support Fine reticular fibres (supporting mesh) provides support to parenchymal cells in the liver

Answer 2

The internal structure is evolves around the several vessels entering or leaving the organ; a) **Portal vein** bringing food-rich blood from the gut. b) **Hepatic artery** bringing arterial blood. c) **Hepatic veins** taking away processed blood from the liver parenchyma into the vena cava. d) **Lymphatics** taking away some lymph/sewage system e) **Hepatic ducts** removing bile to the gallbladder and gut.

Answer 3

Hepatic artery 25% Portal vein 75%

Answer 4

Nerves supply: sympathetic & parasympathetic supply of perivascular structures (fluid filled space around blood vesselss), but very little at sinusoidal level Interestingly, liver can function fine without a nerve supply - evident from liver transplants

Answer 5

Liver is formed of hepatic lobules, which are repeated throughout the liver and are surrounded by connective tissue. In the corners of these lobules you have the portal triad - branch of portal vein, branch of hepatic artery and bile duct - which drain into the lobule Blood from these channels flow down channels (sinusoidal channels) towards the center of the lobule, which is very you find the central draining vein. As the blood passes through the channels, the hepatocytes/epithelial cells carry out their metbalic functions.

Answer 6

a) **Central vein / terminal hepatic venule** - very thin wall; lies in the centre of a lobule, with sinusoids converging towards and opening into it. b) **Sublobular/intercalated vein** - thicker wall; lies alone at the periphery of the lobule - receives blood from central vein c) **Branch of portal vein** - again at the periphery of the lobule - accompanied by one or more small hepatic arteries/arterioles, one or more bile ducts/ductules, and lymphatics. Note - Portal vein, artery, and bile duct constitute a portal triad; the area in which they lie is a portal area. (The lymphatics are ignored for this naming).

Answer 7

Blood from the branches of the portal vein and hepatic artery flows from the outside of the lobule to the centre. As blood moves through the sinusoids it slows down - allowing for the exchange of molecules with the hepatocytes - upstream hepatocytes have more of a sensing role (e.g. nutrients) and signal to hepatocytes downstream, which play more of a regulatory role. Blood is then collected in central veins, goes to sublobular veins, then to collecting veins, and then hepatic veins leaving the liver. Note - In between cells you also have bile ducts (bile canaliculi) – flows occurs in the opposite direction - moves bile towards the gallbladder.

Answer 8

Rappaport's liver acinus represents a functional unit comprising parts of three or so lobules Takes more of a functional perspective for organisation - categorizing based on functional activity/degrees of toxicity of toxic agents - metabolic zonation The territory of an acinus has, as its axis/centre, a branch of the portal vein, and is subdivided into: 1. Periportal (stem cells located here) 2. Intermediate 3. Perivenous (close to the central vein) zones With the initial periportal zone being roughly spheroid, and isolated from periportal zones of adjacent acini.

Answer 9

Sinusoids - low pressure vessels 1. Are lined by fenestrated endothelial cells, loosely attached (gate of the house), and hold phagocytic Kupffer cells (immune surveillance) 2. Fenestrated lining cells are not tightly attached and rest on microvilli of underlying hepatic cells, without a basal lamina intervening. 3. Plasma can thus pass through the sieve plate, formed by the lining cells, out into the perisinusoidal space of Disse (**front garden**) to interact with the hepatocytes. - Some of this fluid may pass to the periphery of the lobule to be collected as lymph. - Disse's 'space' contains ECM materials, but not a visible basal lamina. 4. Scarce, fat-storing, stellate cells of Ito lie outside the endothelial cells. They store vitamin A. They respond to a variety of insults by making collagen and causing cirrhosis (fibrosis) - they can block fenestrations, increaseing pressure in sinusoids

Answer 10

The sinusoidal wall provides for: 1. Blood cleansing, e.g., of gut bacterial toxins; 2. Haemopoiesis in the embryo; 3. Bringing plasma into intimate contact with the hepatic cell for its many metabolic functions.... storage, transformations, syntheses, regulation of plasma concentrations, detoxifications, the production of bile, and assisting defence by producing acute-phase proteins

Answer 11

Hepatocytes are the main functional cells of the liver and perform an astonishing number of functions - 80% of liver mass - high metabolic activity In three dimensions, hepatocytes are arranged in plates that anastomose with one another. The cells are polygonal in shape and their sides are in contact either with sinusoids (sinusoidal face) or neighbouring hepatocytes (lateral faces). Microvilli are present abundantly on the sinusoidal face and project sparsely into bile canaliculi. A portion of the lateral faces of hepatocytes is modified to form bile canaliculi. Hepatocyte nuclei are distinctly round, with one or two prominent nucleoli. A majority of cells have a single nucleus, but binucleate cells are common.

Answer 12

Liver Cirrhosis – characterised by disorganized liver structure, which leads to the hepatocytes no longer receiving the nutrients and oxygen – replace by collagen Stellate cell – can exert good or bad effects on the liver – depending on activity If there are high levels toxins/inflammation (Alcohol – most common cause of liver disease)... 1. Activation of Kupffer cells 2. Retrieves White blood cells 3. Activates stellate cells which convert to fibroblast that produce collagen 4. Collagen seals the fenestrations 5. Increase blood pressure in the sinusoids followed by the portal vein – start of liver cirrhosis

Answer 13

System of canaliculi (need EM to see) between the hepatic cells leads to Canals of Hering/cholangioles - these canals have both hepatocytes and bile duct cells in their walls Canals of hering drain into the bile ductules in the portal areas (small, cuboidal cells, firmly held by membrane interdigitations and junctional complexes, small number of microvilli) Ductules drain into Bile ducts' - epithelium changes to columnar mucous cells and, extrahepatically, the ducts acquire smooth muscle as well as Collagen tissue. Note - Bile flows in opposite direction into the bile duct

Answer 14

Lymph is formed by filtration of plasma into the spaces of Disse as blood flows through the sinusoids. Then lymph percolates between the space of Disse and portal tracts - eventually lymphatics are formed that run along portal vessels and biliary ducts. The exact anatomical correlation between lymphatics and the rest of liver microanatomy is not entirely clear.

Answer 15

1. Glucose metabolism 2. Bilirubin metabolism

Answer 16

1. After feeding - plasma glucose level rise - pancreas responds by producing Insulin from beta cells - signals to the liver to increase glucose uptake, increase glycogenesis and inhibit gluconeogenesis. 2. Fasting state - plasma glucose levels are low - pancreas releases glucagon from alpha cells - decreases glucose uptake/storage, increases glycogenolysis and increases gluceoneogenesis.

Answer 17

Red-blood cell breakdown - heme is processed within macrophages and oxidized to form biliverdin and iron - Biliverdin is reduced to form unconjugated bilirubin, which is released into the bloodstream. Unconjugated bilirubin is bound to albumin in the blood and then taken up by hepatocytes In hepatocytes unconjugated bilirubin is conjugated, in turn making it water soluble. Conjugated bilirubin is excreted into the biliary system In the intestines conjugated bilirubin is converted to urobilinogen by bacterial proteases a) 90% is excreted b) 10% is absorbed and enters the portal circulation and ultimately gets excreted by the kidneys.

Answer 18

Yes, the liver has a wide range of tools available to detoxify and remove any harmful drugs/toxins, in turn allowing them to be excreted in the urine (water soluble products) Relies on the livers cytochrome P450 family System is divided into... 1. Phase 1 metabolism - modification 2. Phase 2 metabolism - conjugation

Answer 19

Simple tests to see how healthy the liver is 1. **Bilirubin** – high levels – likely some sort of blockage in the bile ducts – spilling over in the circulation – jaundice 2. **Aminotransferases** - ALT and AST – enzymes within the hepatocytes – when the hepatocytes are dying, they are released into the bloodstream 3. **GGT and alkaline phosphatase** – damage of bile duct/liver – these are released into circulation - used to see if there is liver/bile duct disease + differentiate this from bone disease (ALP also released in bone disease) - presence of both GGT+ALP indicates liver disease 4. **Albumin + clotting factors** – liver responsible for their production – Low albumin levels or if prothrombin time decrease (marker of clotting), this indicates that the liver isn’t function properly

Answer 20

Yellowing of the skin and eyes - caused by elevated levels of bilirubin in the bloodstream Jaundice might result from increased bilirubin production (prehepatic), diseases that impair hepatocyte function (hepatocellular), or obstruction of the biliary system (cholestatic).

Answer 21

Choletasis - release of bile from the liver is blocked Can be caused by... 1. Gallstones 2. Tumours at the head of pancreas 3. Ampullary lesions All of which then results in jaundice because this causes an elevation in the level of serum bilirubin.

Answer 22

Stomach secretes - pepsinogen, HCL, mucus, gastrin, somatostatin, etc. - Parietal cells - secrete HCL (pH = 2) - important for polypeptide breakdown - PPIs block the proton pump (H+/K+-ATPase) - Neuroendocrine cells a) Enterochromaffin Cells - Histamine b) G cells - Gastrin - drives HCL c) D cells - Somatostatin - inhibits HCL - Other cells: a) Mucus cells - produces mucus barrier b) Chief cells - produce pepsinogen

Answer 23

1. **Amylase** - digestion of carbohydrates - hydrolysis of starch - produced by the mouth and pancreas - product glucose is absorbed in stomach and small intestine 2. **Proteases** - digest proteins a) Pepsinogen converted into pepsin by gastric acid - chief cells in stomach b) Trypsinogen converted into trypsin with the help of enteropeptidases - pancreas c) Chymotrypsinogen converted into chymotrypsin with the help of trypsin - pancreas - Absorption by the small intestine 3. **Lipase** - required for fat digestion - Pancreatic lipase and pancreatic lipase related protein 2 - Bile salts emulsify fats and allow lipases to act

Answer 24

1. B12 absorption 2. Folate absorption 3. Iron absorption

Answer 25

B12 - cobalamin 1. Liberated from protein binding by the action of acid and pepsin in stomach 2. Binds to R factors (cobalamin-binding proteins = haptocorrin, which is secreted by saliva, in bile and by the pancreas) 3. Pancreatic proteases release this complex in duodenum where it is then bound to intrinsic factor (produced by gastric parietal cells) 4. IF-B12 complex absorbed in terminal ileum

Answer 26

If you only remember 3: *Pernicious anaemia (antibodies to parietal cells) *Poor dietary intake *Small bowel Crohn’s disease/post- surgery

Answer 27

Folate - Vitamin B9 - Contained in animal products and leafy green vegetables in polyglutamate form - Cleaved to monoglutamate form in jejunum by folate reductase, which is where it is then abosrbed - Folate/folic acid is not per se biologically active, but is converted into dihydrofolate (by the enzyme dihydrofolate synthetase) in the liver and into tetrahydrofolate by dihydrofolate reductase - Key role in DNA synthesis and repair - Increased use in pregnancy

Answer 28

Causes of deficiency: * Poor dietary intake * Small bowel diseases – coeliac, Crohn’s, resection * Drugs – methotrexate (inhibits dihydrofolate reductase), trimethoprim, phenytoin Deficiency can result in... aneamia, diarrhea and fatal neural tube/brain defects.

Answer 29

Heme iron: * Complexed to heme * Found in meats * In ferrous (2+) form - Well absorbed Non-heme iron: * Vegetables, cereals etc. * Typically in ferric (3+) form - Not well absorbed

Answer 30

Oral iron poorly absorbed (10- 15%) - unabsorbed iron leads to side effects Why is absorption so inefficient? * Because of hepcidin (degrades ferroportin - iron transporter from cells to blood) * High circulating iron is toxic so the body limits increase in plasma iron * High plasma iron - high hepcidin - impairs further iron absorption (up to 48h) Note - hepcidin is the hormone that regulates iron levels

Answer 31

Gastric acid releases Fe3+ complexes, reduces to Fe2+ form and promotes formation of chelates Support by people with achlorhydria (lack of HCL) as they have low levels of Fe3+ absorption - think about the people on PPIs Vitamin C can be used to help reduce Fe3+ to Fe2+ promoting absorption

Answer 32

Simplified concept of metabolism Broken down (catabolic) to produce intermediates that can be used as well as used to produce ATP (energy) and NADPH. Intermediates, ATP and NADPH are then used to produce larger macromolecules (anabolic), which are then brought together to form cell structures

Answer 33

Adenosine Triphophate - energy currency in living organisms High energy phosphate bond is cleaved to release energy to power reactions in the body Note - Effective free energy is lower than actual – due to heat loss

Answer 34

NADPH – electron carrier - used in Redox reactions Provides the reducing power for anabolic reactions and redox balance Nicotinamide - reducing moiety

Answer 35

Starch has two forms – amylose (straight chain) and amylopectin (branching) Amylase breaks both of them down into isomaltose and maltose – which are then broken down to glucose by glucoamylase and isomaltase

Answer 36

Sucrose and lactose – not targeted by amylase Rather they are broken down in the small intestine by sucrase and lactase

Answer 37

Glucose can enter the cell with the help of a transproter or in the case of muscle/liver it can also be obtained locally by breaking down glycogen Glucose-6-P enters glycolysis - producing pyruvate and 2 ATP molecules per glucose - anaerobic Pyruvate enters the mitochondria where it feeds into the TCA cycle and oxidative phosphorylation to produce 30 ATP molecules per glucose - aerobic

Answer 38

Triacylglycerol/triglyceride - glycerol and fatty acids

Answer 39

1. TAG broken down to MAG (Mono-acylglycerol) and fatty acids), which are then absorbed. 2. In the intestinal mucosa TAG is packaged into chylomicrons and transported to adipose tissue, muscle or liver - Adipose tissue - fatty acids are stored/can be released back into circulation - Muscle - can be stored or burnt for energy - Liver - storage/metabolism Key enzyme involved - lipoprotein lipase breaks down chylomicrons - releasing fatty acid and glycerol

Answer 40

TAG and acyl-cholesterol surrounded a core of phospholipids and cholesterol Also contain the fat soluble vitamins

Answer 41

Body has a pool of amino acids and total body protein - which gets depleted as amino acids are used in biosynthetic pathways, energy production and excreted Hence, making protein uptake important to maintain body protein/amino acid pool Also there are numerous essential amino acids that can't be synthesized and thus need to be taken up.

Answer 42

Polypeptides are broken down by proteinases - secreted by the pancreas and small intestine Proteinases show specificity for specific amino acid - cleavage at specific sites. Note proteases are produced and released as zymogens (inactive) - prevents activity inside cells prior to excretion

Answer 43

1. Tissue amino acids undergo transamination - transfer of amino group to form glutamate and carbon skeleton (oxidzed for energy) 2. Glutamate is either converted to alaine and transproted to the liver or transported as glutamine straight to the kidney 3. Liver - glutamate re-foremd from alanine - enters the urea cycle to form urea 4. Kidney - Urea excreted or glutamine amino group cleaved and secreted as ammonium.

Answer 44

Essential vs. non-essential Arg and His – partially essential Glucogenic or ketogenic – yield glucose or ketones

Answer 45

Notes - Two important pools of glycogen – liver and muscle – highly hydrated – not an efficient way to store energy - Muscle – glycogen store used by muscle, rapidly mobilized and anaerobic ATP supply - Triacylglycerol – big energy store/not hydrated but requires O2 for metabolism and NEFA can't be used by brain - Breaking down protein in the body – compromising bodily functions

Answer 46

Glycogen and amino acids converted to glucose – used by body – mainly brain Fat broken down to ketone bodies which can be used by the brain Muscles takes up glucose, ketones and fatty acids, which it uses for energy

Answer 47

Changes in glucose glycogen and gluconeogenesis following a meal - Glucose spikes following a meal - Glycogen stores are topped up - continue to decline if not further added to - liver stores last roughly 1 day (muscle tends to use it's own glycogen stores and not release) - Eventually stores run and the body has to rely on gluconeogenesis to create glucose (glucogenic amino acids and fatty acids) and ketones (ketogneic amino acids and fatty acids)

Answer 48

Summary - Insulin released in resposne to high glucose - drive uptake, storage and usage of glucose, while preventing further release into circualtion Liver – increase glycogen synthesis, decrease glycogen breakdown and inhibits glucose creation Muscle – Increase glucose uptake, glycogen synthesis and protein synthesis and decrease glycogen breakdown Adipose – increase in glucose uptake and TAG synthesis and decrease in fat break down

Answer 49

Type I - Insulin production is low - decreased protein synthesis, increase in lipolysis, decreased TAG synthesis - resulting in weight loss Type II - Insulin is present but tissues are not responding - elevated TAG synthesis and decrease lipolysis resulting in weight gain – explanation: adipose tissue very sensitive to insulin - responding to hyperglycaemia?

Answer 50

Metformin, a drug used in the treatment of Diabetes Mellitus type 2 Effects: 1. Inhibits gluconeogenesis 2. Activates AMP-activated protein kinase - effects shown on image. 3. Acts on intestine – affects microbiome - more effect when ingested, indicating interaction with microbiome

Answer 51

Metabolic syndrome is the medical term for a combination of diabetes, high blood pressure (hypertension) and obesity. Affects 20 – 30 % of population, males > females Characterised by... 1. Increased abdominal fat 2. Dyslipidaemia 3. Insulin resistance – pre-diabetic 4. Impaired glucose tolerance 5. High blood-pressure 6. Cardiovascular disease

Answer 52

No, if it were solely environmental factors then the distribution would shift upwards (proportion of people with a specific BMI) However, a change in the shape of the distriubtion is actually observed, indicating that people are responding differently to the environmental changes - indicating their is a genetic element to the equation.

Answer 53

Microbiome - plays an important role - highly diverse + play a role in fermenting carbohydrates to produce SCFA, account for 6-10% of energy Evidence 1. Mouse studies: correlation of microbiome with obesity 2. Humans: early-life use of antibiotics correlated with obesity later in life 3. Human-to-mouse faecal transfers: effects on obesity depends on source - transfer from obese human to lean mouse - obese phenotype Other elements of health - Metabolic health correlated with diversity of gut bacteria - Other microbiome-derived metabolites may also affect health... e.g. trimethylamine N-oxide - cardiovascular disease, atherosclerosis e.g. elevated plasma [proline] - depression

Answer 54

Peptide hormone (167 aminoacids) Released by adipocytes Circulating levels correlate with body’s fat content - increase adiposity = increase leptin Circulating leptin correlates with BMI Leptin receptors in the brain, including hypothalamus - drive suppression of food intake by... 1. Reducing motivation to feed 2. Reduces rewards for feeding 3. Promotes satiety 4. Increased metabolic rate

Answer 55

97 single nucleotide polymorphisms were identified to be associated with BMI Body weight was found to be ~70% heritable