GI - Nutrition and Digestion Flashcards
What are the organs of the GI tract? What body cavities does the GI tract pass through?
Oesophagus - Thoracic cavity
Majority of GI tract - Abdominal cavity
Terminal sigmoid colon, rectum and anus - Pelvic cavity
What are the standard four layers that form the wall of the GI tract?
The wall of the GI tract is formed of 4 layers:
Mucosa - the lining of the GI tract. Itself comprises 3 layers (Epithelium, lamina propia and muscularis mucosae)
Submucosa – connective tissue. This is where blood vessels and nerves lie
Muscularis – Layers of smooth muscle and enteric nervous system
Serosa – this is the visceral layer of the peritoneum
Some parts of the GI tract have modifications to these standard layers
Function of the mouth? What are the different features found here?
Mouth (oral/buccal cavity)
Key for mastication, speech, start digestion (e.g. starch), some absorption (not subjected to first pass metabolism)
Comprises:
- Lips, cheeks, soft and hard palates
- Tongue (skeletal muscle) with taste buds on papillae
- Salivary glands: submandibular, parotid and sublingual (secrete salivary amylase)
- Teeth
Function of the pharynx in the GI tract?
Function - Swallowing and moving food bolus from the buccal cavity to the oesophagus
The pharynx is typically divided into 3:
1. Nasopharynx
2. Oropharynx
3. Laryngopharynx
What is peristalsis?
Peristalsis is the involuntary contraction and relaxation of longitudinal and circular muscles throughout the digestive tract
Allows for the propulsion of contents beginning in the pharynx and ending in the anus
What are the features of the oesophagus?
Oesophagus
First segment of true digestive tract
Lined with stratified SQUAMOUS EPITHELIUM (thick, robust – cope with tears) until last 1cm (entry to stomach) when COLUMNAR EPITHELIUM starts
Muscle are voluntary (striated) in upper third; involuntary (smooth) in lower third and mixed in the middle.
SPHINCTERS
a) Upper oesophageal sphincter – muscular. Primarily cricopharyngeus. Stops air getting into the gut.
2. Lower oeosphageal sphincter – comprises a thickened muscular layer in the lower oesophagus and cardia of the stomach (intrinsic sphincter) and the diaphragm (extrinsic) - prevents acid/food reflux.
What is an hiatal hernia?
A hiatal hernia occurs when the upper part of your stomach bulges through the large muscle separating your abdomen and chest (diaphragm)
What are the characteristics of the stomach?
Stomach
Variable size. Can hold up to 1.5L,
usually collapsed
Divided into cardia/fundus/body/antrum
Oesophagus enters in the cardia
Exit to the small intestine (duodenum) at the pylorus (pyloric sphincter)
Stomach wall: 4 layers but adapted (muscles lie in oblique layers - strong)
The mucosa is folded into RUGAE (folds) and within these are gastric pits.
What are the different secreting cells found in the gastric mucosa?
Glands: secrete mucous which protects the mucosa from the acid environment of the stomach
Chief cells: secrete enzymes
of gastric juice (pepsin)
Parietal Cells: secrete hydrochloric acid and intrinsic factor (imp for b12 absorption)
Endocrine cells: secrete grelin (hormone which promotes appetite) and gastrin (digestive hormone)
What are the functions of the stomach?
Food reservoir: stores food until ready to be digested
Digestion: started by gastric acids and juices and physically broken down by churning
Secretes intrinsic factor: allows B12 absorption
Some absorption: water, alcohol, some drugs
Endocrine: ghrelin and gastrin secretion
How can we define the lower GI tract?
Any GI structure that is beyond the pylorus of the stomach.
What are the three sections of the small intestine?
Features of the duodenum?
Shortest of the 3
25cms long
Split into 4 sections - D1, D2 (release of pancreatic juice and bile) , D3 and D4
Transitions into the jejunum at the DJ flexure (when abruptly turns)
Features of the jejunum and ileum?
Jejunum approx 2.5ms long
Tranisitions seamlessly into ileum 3.5ms long.
Ileum ends at the ileo-caecal valve in the right iliac fossa
Most absorption takes place here
How does the epithelial surface of the small intestine look like?
The mucosa of the SI is folded into villi –> increase surface area for absorption - in coeliac disease villi are attacked
Enterocytes (surface cells) of the villi are covered in microvilli to further increase SA
Gives a carpet like appearance
Each vilius/villi contains blood vessels and lymph vessel
Other cells found here…
1. Mucus secreting goblet cells
2. Enteroendocrine cells
3. Stem cells - found in deep crypts adjacent to villi.
What are the different regions of the large intestine?
Length 1.5m
Divided into sections:
a) Caecum
b) Colon:
- Ascending
- Transverse
- Descending
- Sigmoid
c) Rectum
d) Anal canal
What are the charateristics & function of the rectum?
Last 15-20cms of large bowel
Funciton - Repository for stool & Absorption of water
Ends at the anal canal where there is a transition to squamous mucosa
Anal sphincter – an internal (smooth muscle) and external (striated muscle)
How is the wall of the colon organised? What are the different layers?
Multiple mucus secreting glands - facilitate passage of hard stool
No villi but crypts
Muscles attached to taenia coli forming ring structures called a haustra
What is a possible function of the appendix?
Appendix - Vestigial organ
Thought to be used as a reservoir for the microbiome following infection
What is the peritoneum?
A continuous membrane that covers most abdominal organs
Two layers
Viseral – lines the organs, is their serosa
Parietal – lines the walls of the abdominal cavity
What do the following terms mean - Intraperitoneal, extraperitoneal, retroperitoneal, mesentry and omentum?
Intraperitoneal – lies within the peritoneum
Extraperitoneal – outwith the peritoneum
Retroperitoneal – extraperitoneal and behind the peritoneum. Organs here include pancreas, kidneys, adrenals, urinary tract, parts of duodenum, colon and rectum.
Mesentry - a large fold of parietal peritoneum that is attached to the small intestine and prevents it knotting up (also blood supply)
Omentum – continuation of the serosa of the stomach. ‘Apron’ hangs over the intestines. If perforation/inflammation it can wrap around the segment and seal it off
Location, characteristic and funciton of gall-bladder?
Lies below the liver
Internally mucosa form rugae (like stomach)
Bile duct joins with pancreatic duct - enters duodenum (D2) at the ampulla of vater
Functions:
- Stores bile, which is crucial for fat absorption
- Triggered by gut hormone (CCK) to empty
Location, function and characterisitcs of the pancreas?
Location:
- Head lies within the curve of the duodenum
- Tail touches the spleen
Characteristics:
- Have an acinar (sac-like arrangement) arrangement like the liver
- Complex ductal collecting system that ends at the pancreatic duct which empties into the duodenum
Function:
Endocrine and exocrine function
- Exocrine (majority of tissue) - Secrete pancreatic juice i.e. Digestive enzymes and sodium bicarbonate
- Endocrine - Islands of endocrine cells ‘islet of langerhans’ which has several kinds of cell - secrete hormones systemically - Most important is insulin (from beta cells) and glucagon (from alpha cells)
How would you define the liver and its function?
Large, lobulated exocrine and blood-processing gland, with vessels and ducts entering and leaving at the porta.
What tissues/structure within and surrounding the liver provide support?
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
What are the different arteries, veins and lymphatic vessels that enter/exit the liver?
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.
What is the proportion of blood supply to the liver from the portal vein and hepatic artery?
Hepatic artery 25%
Portal vein 75%
Outline the nerve supply to the liver? Is it important?
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
Outline the macro-organisation of hepatic lobules in the liver.
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.
What are the three main vessels seen in the liver lobules?
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).
Outline the direction of blood and bile flow in the liver lobules.
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.
Outline what the liver acinus model is - organisation of the liver.
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.
How do hepatocytes interact with the plasma present in the sinusoids?
Sinusoids - low pressure vessels
- Are lined by fenestrated endothelial cells, loosely attached (gate of the house), and hold phagocytic Kupffer cells (immune surveillance)
- Fenestrated lining cells are not tightly attached and rest on microvilli of underlying hepatic cells, without a basal lamina intervening.
- 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. - 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
Three functions of the sinusoidal walls?
The sinusoidal wall provides for:
- Blood cleansing, e.g., of gut bacterial toxins;
- Haemopoiesis in the embryo;
- 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
Outline the organisation of the hepatocytes in the liver.
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.
Outline how stellate cells contribute to liver cirrhosis.
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)…
- Activation of Kupffer cells
- Retrieves White blood cells
- Activates stellate cells which convert to fibroblast that produce collagen
- Collagen seals the fenestrations
- Increase blood pressure in the sinusoids followed by the portal vein – start of liver cirrhosis
Outline the organisaiton and flow of bile ducts/bile in the liver?
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
Outline the formation and movement of lymph in the liver.
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.
Outline the role of the liver in glucose metabolism.
- 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.
- Fasting state - plasma glucose levels are low - pancreas releases glucagon from alpha cells - decreases glucose uptake/storage, increases glycogenolysis and increases gluceoneogenesis.
Outline the role of the liver in bilirubin metabolism.
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.
Does the liver play an important role in the detoxification of toxins/drugs?
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
What are 6 things that are measured in a liver function test? What do they tell us?
Simple tests to see how healthy the liver is
- Bilirubin – high levels – likely some sort of blockage in the bile ducts – spilling over in the circulation – jaundice
- Aminotransferases - ALT and AST – enzymes within the hepatocytes – when the hepatocytes are dying, they are released into the bloodstream
- 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
- 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
What digestive substances are secreted in the stomach and which cells are responsible for their secretion?
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
What are some causes of B12 deficiency?
If you only remember 3:
*Pernicious anaemia (antibodies to
parietal cells)
*Poor dietary intake
*Small bowel Crohn’s disease/post- surgery
Describe what the following flow diagram is trying to communicate.
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
What is ATP? What is it used for?
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
What is NADPH? What is it used for?
NADPH – electron carrier - used in Redox reactions
Provides the reducing power for anabolic reactions and redox balance
Nicotinamide - reducing moiety
Provide an overview of some enzymes released by each organ in the picture.
note - oesophagus is referring to the mouth
Outline the digestion/break-down of starch in glucose (amylose and amylopectin).
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
Outline the breakdown of sucrose and lactose into glucose.
Sucrose and lactose – not targeted by amylase
Rather they are broken down in the small intestine by sucrase and lactase
Outline how glucose is used to make ATP.
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
What are the consituent parts of lipids?
Triacylglycerol/triglyceride - glycerol and fatty acids
Outline the metabolism of dietary fats - from absorption, transport and use in the body.
- TAG broken down to MAG (Mono-acylglycerol) and fatty acids), which are then absorbed.
- 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
What are chylomicrons?
TAG and acyl-cholesterol surrounded a core of phospholipids and cholesterol
Also contain the fat soluble vitamins
Why is maintaining protein uptake important?
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.
How are ingested proteins broken down?
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
Outline the basics of nitrogen metabolism (urea excretion).
- Tissue amino acids undergo transamination - transfer of amino group to form glutamate and carbon skeleton (oxidzed for energy)
- Glutamate is either converted to alaine and transproted to the liver or transported as glutamine straight to the kidney
- Liver - glutamate re-foremd from alanine - enters the urea cycle to form urea
- Kidney - Urea excreted or glutamine amino group cleaved and secreted as ammonium.
How can the different amino acids be classified?
Essential vs. non-essential
Arg and His – partially essential
Glucogenic or ketogenic – yield glucose or ketones
Where do fats, carbs and protein feed into ATP synthesis (pathway entrance into glycolysis or TCA)?
What are the different energy stores in the body? Outline what they are used for + advantages/disadvantages.
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
What energy stores are used in a fasted state?
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
Where does glucose, ketogenic aminocaids, glucogenic amino acids, fatty acids and ethanol enter glycolysis/TCA cycle?
Note -
What does the following graph display?
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)
What effect does insulin have on the liver, muscle and adipose tissue?
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
What are the characteristics of type I and type II diabetes? How does it present? What health conditions is it associated with?
How do type I and type II diabetes differ in terms of their effect of glucose and lipid metabolism?
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?
What is metformin? How is it used to treat type II D?
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
Can increasing levels of obesity solely be attributable to environmental factors?
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.
What links exist between obesity and the microbiome?
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
Outline the roles of ghrelin, cholecystekinin, gastric inhibitory peptide and Peptide YY, in controlling hunger and insulin secretion.
Outline the roles of ghrelin, cholecystekinin, gastric inhibitory peptide and Peptide YY, in controlling hunger and insulin secretion.
