Alimentary System Flashcards
1
Q
Mid GI symptoms
A
Abdominal pain, steatorrhea (fatty stool), diarrhoea, distension
2
Q
Upper GI symptoms
A
Haematemes, black/tar like stool, nausea, vomiting, dysphasia, odynophagia, belching, acid reflux
3
Q
Lower GI symptoms
A
Abdominal pain, bleeding, constipation, diarrhoea, incontinence
4
Q
Hepatobiliary symptoms
A
Right-upper quadrant pain, biliary colic, jaundice, dark urine, pale stool, ascites
5
Q
What is the function of the oesophagus?
A
Conduit for food, drink and swallowed secretions from pharynx to stomach
6
Q
Describe the structure of the oesophagus, including type of epithelium.
A
Non-keratinising stratified squamous epithelium Has skeletal muscle at the top and smooth muscle at the bottom. Muscle arrange in circular and longitudinal arrangements.
7
Q
How does the oesophagus move a bolus of food from the mouth to the stomach? (Include process of swallowing)
A
Oesophagus moves food down by peristalsis where the muscle above the bolus contracts and that below relaxes pushing food down. Topically active When swallowing starts message goes to brain leading to opening of upper and lower oesophageal sphincter. Once food passes upper the sphincter closes. Lower remains open until food enters the stomach.
8
Q
What is the function of the stomach? (3 parts)
A
- Break down food into smaller particles (due to acid and pepsin).
- Hold food and release at a controlled, steady rate into the duodenum.
- Kill parasites and certain bacteria
9
Q
What is the function of chief cells? What happens to their product?
A
They secret pepsinogen. Pepsinogen is the inactive form of Pepsin. It is activated when in a low pH environment pepsinogen proteins cleave one another forming the active form
10
Q
What are the function of parietal cells?
A
They secrete HCl
11
Q
What are the three phases involved in acidic control of the stomach? Describe what happens.
A
- Cephalic phase: thoughts, taste, smell of food activate the vagus nerve (parasympathetic). This increase acetylcholine release and so more acid is secreted from parietal cells
- Gastric phase: - stomach distension detected by stretch receptors lead to more acid - local systems (enteric nervous system) play a part - chemoreceptors detect increase in pH and gastrin is secreted
- Intestinal phase - usually inhibitory. When intestine detects acidic chyme sends protein signals via blood to stomach inhibits acid production - can stimulate production if proteins are not sufficiently broken down
12
Q
What is gastrin? What does it do?
A
It’s a protein that is secreted in response to an increase in pH in the stomach. It triggers the parietal cells to release more acid, and histamine release from other cells in the stomach
13
Q
What are the main organs of the digestive system?
A
Stomach, large intestine, small intestine, pancreas, gall bladder, liver, oesophagus
14
Q
What is the function of the small intestine?
A
To absorb nutrients, salt and water
15
Q
What type of epithelial are present in the small intestine and what is their function? How are the cells specialised for their function?
A
Simple columnar - absorption and transport of substances - microvilli making a brush border. On top of brush border a layer of glycocalyx
16
Q
What is glycocalyx made of and what is its function?
A
Carbohydrate later protecting the lumen but allowing absorption. Has digestive enzymes mixed in in the small intestines. (In large intestine it doesn’t)
17
Q
What is the function of goblet cells? How does their abundance change as you pass down the bowel and why?
A
They secret mucus facilitating movement of material through the bowel and also traps bacteria and particulates. There is increasing abundance of goblet cells as you pass down the bowel because the material becomes more solid as water is drawn out so much mucus is needed to move it along.
18
Q
Where are paneth cells found and what is their function?
A
Found in the crypts of small intestine. They contain acidophilic granules containing lysozyme which kills pathogens. Also glycoproteins and zinc secreted which are needed by some enzymes. Help control flora
19
Q
What is the function of enteroendocrine cells? Where are they found? What is the difference in their abundance between the small intestine and large intestine?
A
They are found in lower parts of the crypts and are hormone secreting cells. More in the small intestine than in the large. This is because hormone regulated processes from small intestine are more complex and require more careful control.
20
Q
Describe the rapid turnover of enterocytes in the small intestine and why this is advantageous in some circumstances?
A
The rapid turnover is achieved because the enterocytes have a very short life span. Those at the tips of the villus die quickly and are sloughed off by contents. They are then incorporated into the chyme in the lumen of the small intestine. New enterocytes are formed in the crypts where the stem cells rapidly divide and the cells move up the villus in a manner similar to an escalator. The rapid turnover means that agents interfering with cell function or metabolism have reduced effects and lesions are short lived. E.g. Cholera toxin is survivable so long as the patient remains hydrate because the cells effected die after a few days and the disease is therefore short lived.
21
Q
What are the differences and/or identifying features of each section of the small intestine (duodenum, jejunum and ileum)?
A
Duodenum has brunner’s gland (secrete alkaline fluid neutralising acid chyme) Jejunum characterise by numerous, large folds in sub-mucosa = plicae ciculares. These are taller, thinner and more frequent than in other sections of the small intestine. Ileum has lots of peyer’s patches to prevent bacteria moving from large intestine into the small intestine
22
Q
How is motility achieved in the small intestine (the different types of movement)?
A
Segmentation: mixes contents and occurs by stationary contraction of circular muscles at intervals.
Non organised Peristalsis: involves sequential contraction of adjacent rings of smooth muscle propelling chyme along around 10cm
23
Q
How does the digestion of proteins occur?
A
Pancreatic proteases are secreted as precursors and activated in the duodenum by enterokinase. Trypsin activates other proteases. Brush border also contains some proteases. Di and tri peptides and single AA absorbed into enterocytes by facilitated diffusion and secondary active transport. Di and tri peptides are broken down by cytoplasmic proteases. Note: pancreas secrets enzymes with a trypsin inhibitor to prevent auto digestion of the bile duct and ensuring enzymes are only activated in the small intestine
24
Q
How are carbohydrates digested and absorbed?
A
Pancreatic amylase digests complex carbohydrates into disaccharides and olgiosaccharides. This are converted into monosaccharides by brush border enzymes such as Maltese, lactase and sucrase. Absorption occurs via facilitated diffusion (e.g. Fructose via carrier glut-5) or secondary active transport (e..g glucose coupled with na+ via SGLT-1).
25
What is the portal triad and in what direction do blood and bile drain?
Portal triad = branch of hepatic portal vein, branch of hepatic artery and bile duct Blood drains from triad to central vein, bile drains towards triad
26
How is bile secreted?
Bile is secreted from the apical surface of hepatocytes and drains via the canalicular network to bile ductiles.
27
How is the blood supplied to the liver? How much of the cardiac output does the liver use?
Dual supply. 20% comes from hepatic artery and 80% from hepatic portal vein. Uses 25 % of cardiac output
28
What is the function of hepatocytes? How are they specialised to fulfil their function?
Perform most major functions of the liver. The apical part is bound to bile canaliculi. - protein synthesis - metabolism of amino acids - carbohydrate metabolism - lipid metabolism - drug metabolism/detoxification
29
What do hepatic stellate cells do?
They are involved in vitamin A storage and reside in the space of disse. In disease they are major pathway for fibrogenesis. They are activated and form fibroblasts.
30
What do kupffer cells do? Where are they found?
They are sinusoid and phagocytose RBC (also use lysosomal activity to break them down)
31
Cholangiocyte function?
Modification of bile: this occurs via coordinated transport of various ions and solutes and water
32
What is the function of the liver?
Digestion, bile posy thesis, energy metabolism, degradation and detoxification
33
Describe the role of the liver in blood glucose metabolism?
Stores glycogen which can be broken down into glucose and used to raise levels.
**_Cori-cycle:_** lactate produced in skeletal muscle travels to liver were it is converted back into pyruvate. The pyruvate returns to skeletal muscle so that it can be used in respiration. Amino acids and deamination forming pyruvate which can form glucose Triglycerides are broken down to form glucose
34
Describe the livers role in protein metabolism?
Synthesis 90% of plasma proteins which carry out important roles in blood clotting, binding/carrier proteins for hormones and help maintain blood osmotic pressure. Metabolism of amino acids results in production of toxic ammonia. This is converted into inert urea which is excreted. Transamination: exchange of amino acid group on one acid with a ketone group on the other acid. For many glutamic acid is an intermediate particularly for those without a suitable precursor. Deamination: conversion of amino acids to corresponding keto acid by removal of amine groups as ammonia and replacing it was ketone group. Occurs primarily on glutamic acid.
35
Describe fat metabolism in the liver.
Excess glucose and amino acids can be converted into fat as storage when the liver glycogen store is full it's converted into fat.
The liver synthesis lipoproteins, cholesterol and phospholipids. The liver convert 2 acetyl-coA into acetoacetic acid for transport to other tissues as a energy supple. Once there it's converted back into acetyl-coA Fatty acid via **beta oxidation** creating acetyl coA which enters the TCA cycle in liver.
Ketone bodies can be made in liver from fatty acids. They can travel in blood and be an energy supply (e.g used by brain) Lipoproteins are formed and cholesterol ester transfer protein shuffles cholesterol from HDL to LDL.
36
Describe formation of bile acids. What are the components?
Bile salts, cholesterol, bilirubin, HCO3- and water. Cholesterol is converted into colic acid and chenodeoxycholic acid.
They are then carboxylated and hydroxylated to increase water solubility. They are conjugated with tauricholic and glycocholic acid to form bile acids, this forms **primary bile acids**.
Secondary bile acids are de-conjugated and de-hydroxylated primary bile salts. This is done by GI bacteria.
37
Describe how bile salts emulsify fats in the intestine. Describe how bile salts are recycled.
Bile salts emulsify fats into small drops in an aqueous medium. The emulsified fats are broken down from triglycerides into fatty acids by lipases. The glycerol is then wrapped in bile salts to form micelles. The micelles then comes into contact with mucosal wall. Then recycled to move more lipids into enterocytes. Finally the bile salts are actively reabsorbed in terminal ileum. It passes via the hepatic portal vein back to the liver were they can be desecrate again
38
Describe lipid digestion
1. Secretion if bile (bladder) and lipases (pancreas)
2. Emulsification: bile salts suspend fats in lipid droplets (increase surface area for digestion)
3. Enzymatic hydrolysis of ester linkages: triglycerides are converted into 2 fatty acids and monoglycerides.
4. Solubilisation of lipolysis products in bile salt micelles
On entering enterocytes the monoglycerides and free fatty acids are processed in 2 pathways:
1. Monoglyceride acylation (major)
2. Phosphatidic acid pathway (minor)
Triglycerides combine with proteins, cholesterol, phospholipids and trace carbohydrate to form chylomicrons. Chylomicrons pass through basement membranes and enter lacteals.
39
What does the larder function?
Stores fat soluble proteins (A,D,E and K and B12). Also stored ferritin for RBC production. Stores fat and glycogen.
40
How is the liver involved in vitamin D?
Ca2+ metabolism: UV light converts cholesterol to vitamin D precursor. The precursor needs to be hydroxylated twice. The first of which occurs in the liver and the second in the kidney.
41
What is the function of the large intestine?
Reabsorption of electrolytes and water and eliminating of undigested food
42
What are the layers surrounding the lumen (in particular muscle) in the small intestine? What are the differences in the large intestine?
From lumen to the outside: Mucosa (epithelial cells, goblet cells, cells in crypts etc) ➡️ submucosa ➡️ circular muscle ➡️ longitudinal muscle ➡️ serosa In the large intestine the longitudinal muscle is concentrated into 3 bands : taenia coli which are essential for motility and formation of haustra (pouch of intestine)
43
How is the large intestine supplied with blood? Which area is most susceptible to ischaemia?
Proximal transverse colon is supplied by middle colic artery. Transverse colon is perfumed by inferior mesenteric artery Region between the 2 is sensitive to ischaemia.
44
How does the colon absorb water and electrolytes? Overview
Na+ and cl- ions are absorbed by exchange mechanisms and ion channels. The water then follows by osmosis and k+ moves out into the lumen.
45
Describe movements of large intestine.
Colonic contractions is a kneading prices but minimally propulsive. In proximal colon anti-propulsive patterns dominate to retain chyme and try and remove as much water and electrolytes. In transverse and descending: localised segmental contractions of circular muscle causes mixing Short propulsive movements every 30 minutes and more frequently post meal 1-3 days there is a mass movement such as a peristaltic wave. Properly move to around 1/3 to 3/4 of the length of the colon
46
How is the large intestine innervated?
Parasympathetic: innervated ascending colon and most of the transverse colon by vagus nerve. Distal is by pelvic nerves. Sympathetic: innervated via the lower thoracic and upper lumbar spinal cord
47
Describe the process of defecation
Defection is controlled by reflex and voluntary. Reflex opens the internal sphincter but the external is under conscious control. Peristaltic waves move the faeces down and out of the anus. The last bit is called the social rectum and can distinguish between solid, gas and liquid.
48
What functions do the intestinal flora do?
Synthesis and excrete vitamins Prevent colonisation by pathogens through competition Antagonise other bacteria through production of substances that inhibit/kill non-indigenous species. Stimulate cross-reactivity antibodies preventing invasion Help break down some fibre.
49
Describe the endocrine function of the pancreas.
The pancreas has areas called islets that are responsible for its endocrine functions. It is largely involved in blood glucose control Alpha cells = glucagon, beta cells = insulin, delta cells = somatostatin
50
Describe the exocrine function of the pancreas? How are the product secreted. What are the function of the secretions?
The pancreatic juices are secreted via the bile ducts. Duct cells secrete high volume, watery solution with a very high bicarbonate concentration. The bicarbonate neutralises the acidic chyme that enters the duodenum. The solution also washes down the enzymatic solution prevent blockages in the ducts. Acinar cells produce zymogen granules (pro-enzymes) which contain enzymes which are involved in digestion. This is a viscous solution.
51
How is bicarbonate produced in the pancreas?
Bicarbonate is formed with carbon dioxide and water is converted into protons and bicarbonate by carbonic anhydride, the bicarbonate is pumped into the lumen via cl-/HCO3- exchange and the protons release into blood via na+/h+ exchange,
52
How is bicarbonate secretions from pancreas controlled ?
When chemoreceptors in the duodenum sense the acidic chyme. The cells secrete secretin which moves via the blood to the pancreas. This stimulates bicarbonate release (increase cAMP in pancreatic cells and bicarbonate moves out). This stops when neutralisation of chyme occurs the stimulus for secretin release is stopped. So bicarbonate release is reduced. The duodenum also secreted CCK which stimulates enzyme release hut it has a potentiating effect for secretin rapidly increasing bicarbonate release. This means neutralisation occurs more quickly and duodenum is not exposed to damaging acidic pH.
53
How is enzyme secretion from the pancreas stimulated and inhibited?
cholecystokinin is secreted by the duodenum in response to fats/proteins/lipids. This stimulated enzyme secretion from the pancreas. When these are digested the stimulus no longer exists and CCK isn't secreted
54
What are the 8 important features important to describing abdominal pain?
SOCRATES Site, onset, character, radiation, associated symptoms, timing, exacerbating/relieving factors, severity
55
What are the 8 important features important to describing abdominal pain?
SOCRATES Site, onset, character, radiation, associated symptoms, timing, exacerbating/relieving factors, severity
56
Describe pancreatitis. Incidence, common causes, symptoms, treatment. What are the 2 main types.
There is an acute and chronic form, but there are other forms as well. 17 new cases per 100,000 Symptoms: varying symptoms but abdominal pain (epigastric radiating back), nausea, committing. The patient may be very unwell and be in shock. Common causes: GET SMASHED Gall stones, ethanol (two most common) Trauma, steroids, mumps, autoimmune, scorpion venom, hyperlipidaemia/hypercalcaemia. ERCP, drugs Treatment: observations and monitoring, nutritional support
57
What are the complications for pancreatitis?
Systemic: hypovolaemia,hypoxia, hypocalcaemia, hyperglycaemia, DIC and multiple organ failure, Localised: pancreatic necrosis, fluid collections, splenic vein thrombosis and chronic pancreatitis.
58
What are the cancer types corresponding with: Squamous epithelial Glandular epithelium Enterochromaffin cells Interstitial cells of Cajal Smooth tissue Adipose tissue
Squamous epithelial = squamous cell carcinoma Glandular epithelium = adenocarcinoma Enterochromaffin cells = carcinoid tumours Interstitial cells of Cajal = GI stromal tumour Smooth tissue = leiomyoma Adipose tissue = lipomas
59
Consider journey from reflux to acid. Describe Barrett's oesophagus and management options.
Reflux ➡️ inflammation ➡️ Barrett metaplasia ➡️ dysplasia ➡️ carcinoma Those with Barrett has a slight increase in oesophageal cancer but not drastically do. However when signs of dysplasia start the increase in risk is more dramatic. Patients with high level dysplasia need to have regular endoscopy and resection of areas is recommended.
60
Colon cancer: symptoms, risk factors.
Many are asymptomatic or have unexplained anaemia. Others may have change in bowel habit, blood in stool or acute intestinal obstruction. Risk factors: family history, specific hereditary conditions, uncontrolled ulcerative colitis, age, previous polyps
61
Pancreatic cancer: symptoms, prognosis and risk factors.
Prognosis: 18% 1 year survival. 2% 5 year survival rate Early symptoms: depression, abdominal pain, glucose intolerance, loss of appetite, weight loss Later symptoms: jaundice, further weight loss, ascities (fluid build up), gall bladder obstruction Risk factors: smoking, drinking, obesity, family
62
what are the 2 types of active transport and give examples?
primary active transport that is linked to cellular metabolism -e.g na+/k+ ATPase secondary active transport uses energy derived from the concentration gradient of another substance e.g. SGLT-1 cotransporter, Na+/H+ counter transporter
63
how is sodium transported into enterocytes in: proximal bowel jejunum ileum colon
proximal bowel: counter-transport exchange with H+ jejunum: co-transport with AA and monosaccharides ileum: co-transport with Cl- colon: restricted movement of ions
64
how is water absorbed in the large intestine?
Na+ is actively transported into intercellular spaces by Na+/K+APTase and replaced in enterocytes by absorption from lumen. HCO3- and Cl- are transported out due to electrical potential created by movement of sodium. Intercellular space becomes HYPERTONIC so water flows into the space via osmosis through transcellular and paracellular pathways. Water distends intercellular channels increasing hydrostatic pressure resulting in water and ions being pushed into blood vessels.
65
Where in the GI tract is calcium absorbed and how?
Duodenum and ileum Calcium crosses membrane via interstital calcium binding proteim (IMcal). In cytoplasm it binds to calbindin. Calcium is pumped across basolateral membrane by plasma membrane calcium ATPase (PMCA) and Na+/Ca2+ exchanger
66
why is calbindin important in calcium absorption?
it prevents Ca2+ acting as a messenger
67
Where is iron absorbed and describe the process.
duodenum heme is internalised by heme carrier protein 1 (HCP-1). Fe2+ is liberated by heme oxygenase.
* Fe3+ in lumen is converted to Fe2+ by duodenal cytochrome B.
* Fe2+ enters cells by divalent metal transporter 1 (DMT-1). Fe2+ binds to unknown factors and leaves cell by ferroportin ion channel. it may be converted to FE3+ in blood by hephaestin.
* Fe3+ then binds to apotransferrin and travels in this form around the blood. to reduce the about being absorbed and prevent toxic effects the Fe2+ in the cell may be converted into Fe3+ which binds to cytosol apoferritin which group to form a ferritin micelle. The iron is lost when the cell dies and sheds into lumen and is excreted.
68
how is vitamin B12 absorbed and in what part of the intestine? where is B12 Stored?
Ileum. stored in liver B12 binds to R proteins made by parietal cells in the stomach to prevent digestion and move into small intestine. There the R proteins are removed and intrinsic factors (IF) bind to B12. IF also made by parietal cells. B12/IF complex travels to distal ileum where cubilin receptors on enterocytes bind to the complex. complex enters cell and the IF is removed by the mitochondria. Transcoblalmin II (TCII) is added to B12 and the new complex leaves cell and enters blood in an unknown mechanism. travels in blood till the liver which has TCII receptors. the complex binds and enters the liver. Here TCII is removed and B12 is stored.
69
Describe all the organs food passes through in the GI tract before waste is expelled.
Mouth, oesophagus, stomach, small intestine compromising of duodenum ➡️ jejunum ➡️ ileum, passing into large intestine compromising of caecum ➡️ ascending colon ➡️ transverse colon ➡️ descending colon ➡️ sigmoid colon
70
How can microbes interact with the host (2 mechanism)?
Either through direct interaction with host cells or via metabolites and proteins they produces
71
What are the 3 major classes of bacteria found in the human GI tract?
Firmicutes Bacteroidetes Actinobacteria
72
In what ways might microbiota be an asset?
Defence (bacterial antagonist) Priming mucosal immunity Peristalsis Metabolism of dietary carcinogens Synthesis of B and K vitamins Epithelial nutrients (e.g. Small chan fatty acids - butyrate) Conversion of products Utilisation of indigestible carbohydrates
73
No what ways might microbiota be a liability?
Pro carcinogens converted into carcinogens Overgrowth syndromes Opportunistic infections Essential for IBD Utilising indigestible carbohydrates may contribute to obesity Role in insulting resistance and non-alcoholic fatty liver disease
74
Describe normal bilirubin formation and metabolism.
FORMATION: haem (from RBC mainly) is broken down in the spleen to biliverdin by haem oxidase. Biliverdin ➡️ bilirubin by bilirubin reductase. This is UNCONJUGATED BILIRUBIN. It binds to albumin and travels to the liver via blood. The hepatocytes take up bilirubin (extracting it from albumin) via organic anion transporters. Bilirubin binds to ligandins. Bilirubin is conjugated forming bilirubin diglucuronide ( makes up most of it) and bilirubin monoglucuronide by UGT (bilirubin-diphosphotase glucuronosyl transferase). The conjugated bilirubin is transported into canaliculi by cMOAT. Bilrubin conjugate is water soluble so is not absorbed In small intestine. In large intestine bacterial beta-glucoronides hydrolyse the conjugated bilirubin forming non-polar urobilinogen. This is absorbed in very small quantities in the large intestine, the rest is secreted. What is absorbed is re-excreted by the liver and kidneys.
75
What are the identifying features of pre-hepatic jaundice? What may cause pre-hepatic jaundice?
Higher unconjugated bilirubin, total bilirubin elevated, normal alkaline phosphatase and ALT. inherited disorders of bilirubin metabolism - Gilbert's Increased haemolysis Massive transfusion Haemorrhage reabsorption Inefficient erythropoiesis
76
What characterises hepatic jaundice? What are common causes?
Elevated bilirubin and ALR, minor changes in alkaline phosphatase Hepatitis, metabolic liver disease Defection uptake, conjugation or excretion of bilirubin
77
Post hepatic jaundice causes and risk?
Risk of sepsis and occurs due to defective transport of BR to duct system e.g. Stones in the ducts
78
What is liver failure? What are the different subtypes? Causes of liver failure by type?
Insufficient hepatocytes function to maintain normal homeostasis. Acute: hyperactive, acute, subacute - paracetamol overdose, viral hepatitis, pregnancy, vascular disease, metabolic causes Chronic - hep B and C, alcoholic liver disease, autoimmune, non-alcoholic fatty liver disease
79
A patient has recently been diagnosed with lower-oesophageal cancer. They have a long standing history of gastrooesophageal reflux disease. What type of tumour would most likely have been confirmed by biopsy?
Adenocarcinoma
80
What pathophysiology is the splenic flexure of the colon particularly susceptible to?
Ischaemia
81
Following a serious bout of ulcerative colitis, a patient is given a full colectomy (removal of colon from caecum to anus). How will this affect the reabsorption of bile salts?
5 % reduction
82
What type of bacterial phylum is most abundant in the gut?
Bacteriodetes
83
What do alpha cells secrete? What is the role of secretion?
Glucagon
It converts glycogen to glucose
84
What do beta cells secrete? What is the role of secretion?
Insulin
Insulin triggers the conversion of glucose to glycogen
85
What do delta cells secrete? What is the role of secretion?
Somatostatin
Various functions that down regulate the GI tract
86
What do acinar cells secrete? What is the role of secretion?
Trypsinogen, chymotrypsinogen, procarboxypeptidase
Function of trypsinogen, chymotrypsinogen and procarboxypeptidase: protease precursor
Pancreatic lipase
* fat digestion
Pancreatic amylase
* carbohydrate digestion
87
What do duct and centroacinar cells secrete? What is the role of secretion?
Bicarbonate
* neutralises acidic chyme in small intestine
Sodium:
* facilitates H2O secretion by creatgin an osmotic gradient
Water:
* solution for enzyme secretions preventing blockage
88
What non-immune mechanisms of defence are present in the gut?
* **chemical barriers**: gastric acid and proteases
* **normal oral and gut flora**: compete with potentially pathogenic bacteria
* **anatomical barriers**: enterocyte membrane, peristalsis and muscus
* **paneth cells**: they produce defensins and lysozymes
89
What are some of the most common causative agents of traveller's diarrhoea?
Bacteria: e. coli, shigella, salmonella, cholera
Virus: rotavirus, norovirus
Protazoa: giardia
90
What part of the GI tract has a high abundance of MALT (mucosa associated lymphoid tissue)
Oral cavity - inparticular tonsils
91
What are the 2 types of GALT (gut associated lymphoid tissue) and where are they found/what do they involve?
NOT ORGANISED:
* intra-epithelial lymphocytes
* lamina propria lymphocytes
ORGANISED:
* cryptopatches
* peyer's patch
* isolated lymphoid follicles
* mesenteric lymph nodes
92
What does GALT secrete?
IgA (secretory and intersitial), IgG, IgM and involved in cell mediated immunity.
93
Where is Peyer's patch most commonly found and what membrane covers it?
distal ileum has highest abundance but found throughout small intestine quite commonly.
covered by follicle associated epithelium
94
How does the peyer's patch lead to an immune response?
M cells in the follicle associated epithelium sample antigents. Antigens can then be endocytosed and move to sup-epithelial dome which contains dendritic cells. Dendritic cells process the antigens and present them to the naive B and T calls in the Peyer's patch
Lymphoctyes may travel to lymph nodes to proliferate
95
What is the role of IgA in the GI tract?
The dimeric structure helps it to bind to luminal antigens and therefore prevent invasion and adhesion of bacteria.
96
How does gut homing work?
Lymphocutes proliferate in mesenteric lymph nodes before enetering general circulation. These lymphcytes express receptors for chemokines and integrin expressed by gut tissue - this give it some gut homing characteristic.
Addistionally cells in GALT have a higher affinity for lymphocytes with these characteristics.
combined this helps the lymphocytes return to the gut
97
How is tolerance achieved in the gut?
Suppresion of antigen response is achieved by:
* deletion of responding lymphocytes
* T cell anergy
* treg cell function
98
What is oral tolerance?
this has 2 parts.
Firstly if you repeatedly eat an antigen leading to exposure to high doses anergy occurs (irreversible)
exposure to low doses of antigens can lead to tolerance (reversible)
99
Describe the 2 pathogenesis for coeliac disease, common symptoms and treatments.
Pathogenesis 1: inappropriate immune response to gliadin in wheat. Gliadin is modified by TGG enzyme. Modified compound binds with high affinity to MHC class II leading to a T cell response
Pathogenesis 2: the modified compound remains bound to TGG enzyme and the complex is recognised by B cells leading to a response
symptoms: bloating, fatigue, weight loss, vomiting, oedema
treatment is to remove gluten from diet
100
What 2 conditions are under the umbrella term of inflammatory bowel disease?
Crohn's disease and ulcerative colitis
101
What type of energy balance leads to obesity?
positive energy balance where an individual eats more than their energy expenditure
102
What 3 measurements can be used to classify obesity? Which is the most commonly used? Identify any problems with any of the methods.
BMI. \>30 is obese, between 25-30 is overweight
- this is most commonly used because it is easy to calculate and measure, however does not take into accound a person's ethnicity or their tissue type (i.e. muscle weighs more than fat)
waist-to-hip circumference.
females \>0.85, males \> 1.0.
Body fat percentage.
103
What causes obesity?
* energy intake vs expenditure
* over the years we have increased amount of calories from fat and decreased those from carbohydrates (carbs → satiety) and we have become less active so decreased expenditure
* genes
* common obesity is a complex genetics, however amount and site of weight gain has some genetic components
* some monogenic forms of obesity e.g. prader willi
* brain and endocrinology
* white adipose secretes leptin which signals to hypothalamus that there is enough stored and satiety
* rare cases there may be a leptin defiency leading to obesity
* leptin, grehlin and PYY all contribute to satiety so are a good target for weight loss medication
* behaviour and culture
* e.g. more people in lower classes are obese because they can't afford good quality foo
* greater inactivity e.g. sitting all day or driving instead of walking
104
How does obesity effect an individuals morbidity and mortality?
increases it.
it also increases risk of other disease that can effect major organ systems
105
What are some medical problems associated with obesity?
* sleep apnoea
* lung disease: astham and pulmonary blood clots
* stroke
* liver: fatty liver, cirrhosis
* gallstones
* cancer: uterus, breast, prostate, colon, oesophagus, pancreas, kidney
* heart: abnormal lipid profile, high BP
* diabetes
* pancreatitis
* women: infertility & irregular periods
* inflamed veins and blood clots
* gout
106
What is the front line treatment for obesity?
lifestyle changes
- improving quality and decreasing quanitity of food while also increasing exercise
- surgical: these aim to increase satiety and include gastric bypass, gastric sleeve and gastric balloon
- phamacological: orlistate which inhibits pancreatic lipase so more fat is excreted
107
Where is the myenteric plexus located and what does it control?
It is located between the circular and longitundinal muscle layers of the intestine and controls gut motor function
108
Where is the submucosal plexus found and what is its function?
It is found in the submucosa and is involved in sensing the environment within the gut lumen allowing it to co-ordinate blood flow, epithelial and endocrine function.
109
What sympathetic nerves innervate the digestive system?
The greater splanchic and the lesser splanchic form the coeliac ganglion and superior mesenteric ganglion.
The inferior mesenteric ganglion innervates the lower part of the digetive system
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What does the coeliac ganglion innervate?
oesophagus, stomach, abdominal blood vessels, liver, bile duct, small intestine, pancreas and adrenal gland
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What does the superior mesenteric ganglion supply?
Large intestine
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What does the inferior mesenteric ganglion supply?
rectum, kidney, bladder and gonads
113
What are the functions of the GI endocrine system?
* regulation of mechanical process of digestion
* regulation of chemical and enzymatic processes of digestion
* control of post absorptive processes involed in assimilation of digested food and CNS feedback regulating intake
* Effects on the growth and development of the GI tract
114
What is gastrin function? What stimulates and inhibits release?
FUNCTION: gastrin has a role in control of gastric acid secretioon
STIMULI: amino acids and peptides in stomach, gastric distension and vagus nerve stimulation
INHIBIT: when stomach pH falls below 3
115
What is the function of cholecystokinin? What stimulates release?
FUNCTION: a small intestine hormone that stimulates the secretion of pancreatic enzymes and biles
- stimulates pancreatic enzyme release, delays gastric emptying, stimulates gall bladder contraction
STIMULI: fat and peptides in the upper small intestine
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What is the role of secretin? What stimulates it's release? What occurs at high levels?
Secretin is a hormone that stimulates the secretion of bicarbonate rich fluids from the pancreas and liver
STIMULI: prescence of acid in the duodenum (pH less than 4.5)
- in high concentrations it can inhbit gastric emptying and gastric acid secretion
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What cells secrete somatostatin? What does somatosatin inhibit?
It is secreted from endocrine D cells of the gastric and duodenal mucosa as well as the pancrease.
STIMULI: mixed meal
INHIBITS; gastric secretion, motility, intestinal and pancreatic secretions, release of gut hormone, intestinal nutrient and electrolye transport, growth and proliferation
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What is GIP? What effects does it have physiologically?
GIP is secreted by mucosal cells following an ingested meal.
EFFECTS: stimulates insulin secretion
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What cells secrete PYY? What are the effects? How does PYY influence appetite?
secreted from mucosa cells in the **duodenum and jejunum**.
EFFECTS: reduce motility, gallbladder contraction and pancreatic exocrine secretion, it also inhibits intestinal fluid and electrolyte secretion and good intake
PYY inhibits **NPR/Agrp neurones** and **stimulates POMC neurones** therefore **decreasing appetite**. leads to a reduced food intake. lowest before a meal and rises.
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Where is the arcuate nucleus found and what does it do?
found in the hypothalamus it is key to appetite regulation. Receives signals from the brain stem, peiphery and circulating factors (has an incomplete blood-brain barrier allowing exposure to these circulating factors)
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What are the 2 main arcuate neuronal populations involved in appetite control?
**_POMC neurones_**: these contain enzymes that cleave POMC to form α **- MSH** which acts on **MC4 receptor (MC4R)** in the paraventricular nucleus. This leads to ***decreased appetite*** and reduced food intake.
**_NPY/Agrp neurones_**: when these neurones are stimulated they secrete NPY and Agrp (both increase appetite, but focus on Agrp). **Agrp** binds to **MC4R** leadgint to suppression of the "decrease appetited" signal. As a result **appetite increase *(i.e. hunger)*** and eventual food intake occurs.
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What mechanism does leptin have an important role in?
The **adipostat mechanism** whereby the brain can sense the proportion of body mass which is made up of white adipose tissue. This can be achieved using leptin which is secreted from white adipose tissue *in concentrations proportional to fat mass*. It acts on appetite to **reduce appetite**.
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What are some of the physical effects of excessive alcohol intake?
* **CNS:** wenicke-karsakoff syndrome, cerebral atrophy, optic atrophy, peropheral neuropathy (most due to deficiences in nutrients)
* **CVS**: hypertension, alcoholic cardiomyopathy, stroke
* **GI tract**: gastritis, acute pancreatitis, cancer, cirrhosis, alcoholic hepatitis
* **kidneys**: renal failure
* **limbs:** gout, fractures, myopathy
* **endocrine and reproductive**: psuedocushings, infertility, breast cancer, foetal alcohol syndrome
* **psychological**: some patients will develop psychiatric disorders as a result of drinking (e.g psychosis, depression), others will have pre-existing disorders but turn to alcohol as a negative coping mechanism
124
Describe the stages of alchol related liver disease. At what point is the damage irreversible?
chronic alcohol missure → steatosis → hepatic fibrosis → cirrhosis →liver cancer
* steatosis may alternatively develop into steatohepatitis
* irreversible damage caused at cirrhosis
* risk factors for developing **cirrhosis**: female, hemochromatosis, binge drinking, viral hepatitis, HIV, obesity, insuling resistance, smoking
125
What are the associated complicatinons and mortality associated with:
a) 10% loss of lean body mass
b) 20% loss of lean body mass
c) 30% of lean body mass
d) 40% of lean body mass
a) impaired immunity, increased infection - 10% mortality
b) decreased healing, weakness, infection - 30% mortality
c) too weak to sit, pressure sores, pneumonia, no healing - 50% mortality
d) death, usually from pneumonia - 100% mortality
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What are some signs of undernutrition?
* weight loss
* loss of subcutaneous fat
* muscle wasting
* peripheral oedema
* hair loss
* chronic infections
* listless, apathetic
* poor wound healing, pressure sores
* recurrent respiratory infections
127
What passive response occur to a negative energy balance?
Decreasing insulin, decreased thyroxine, glucagon release, growth hormone release, mobilisation of free fatty acids and amino acids
128
What active response occurs to a negative energy balance?
decreases SNS activity, increased catecholamine production, decreased metabolic flux and energy expenditure
129
What causes **beriberi**? What are the symptoms and possible complications?
**deficiency of thiamine (B12 derivative)** needed for release of energy from food and nerve function.
SYMPTOMS: sever lethargy and fever
COMPLICATIONS: affect CVS, nervous, muscular and GI system
130
What causes Pellagra?
**deficiency of naicin (B3 derivative)** which is important for the formatin of co-enzymes such as NAD and NADP
