Alimentary Flashcards
Layers of the gut
Mucosa- epithelium, glands and lamina proper
Submucosa-connective, submucosal plexus
Muscularis-circular and longitudinal
Serosa/Adventita
Oesophagus
Stratified squamous
Upper oesophagus- skeletal muscle
Lower oesophagus- smooth muscle
Oesophageal sphincters
Upper-2 muscles- constrictor pharyngeal medius
-constrictor pharynges inferior- voluntary
Lower- 2 components- internal- circular
External- formed by diaphragm
Change from oesophagus to stomach
Z line
Stratified Squamous to columnar
Swallowing
Originally both spinsters closed
Then both open as food goes to end of pharynx
Then upper sphincter and superior rings contract and inferior rings dilate
Then after food passes through lower sphincter it contracts- pushing it into stomach
Functions of stomach
Digestion
Storage- reservoir until downstream ready
Immunological protection
Stomach wall
Similar structure to rest of GI tract but has extra oblique layer of smooth muscle in circular muscle- aiding grinding motion
Gastric pits
Deep pores in mucosa containing gastric glands that produce HCL, enzyme, zymogens and mucus
Mucous Cells
Produce mucous that protects mucosa from highly acidic substances, since it also contains bicarbonate.
Also protects the layer from enzymatic action
Parietal Cells
Produce HCL, usually in response to gastrin
Causes activation of carbonic anhydrase, in which bicarbonate is exchanged for Cl- and H+ is exchanged for K+ which enters the cell via Na/K pump
Chief Cells
Produce zymogen pepsinogen (prevents breakdown of chief cell)
Which is activated by low pH to pepsin which breaks down dietary proteins
Also produces gastric lipase
G cells
Endocrine cell that produces gastrin in response to vagus innervation, presence of peptides and stomach distention
Travels via blood and causes smooth muscle contraction, acid secretion, pyloric sphincter relaxation
Enterochromaffin like cells
Respond to gastrin and produce histamine which activated HCL production
D cell
Secrete somatostatin which inhibits GI function such as histamine and HCL production
Phases of stomach activity
Cephalic- response to smell and though of food
Vagus causing production of mucus, HCL and pepsin- for short period
Gastric- response to distention of stomach and chemoreceptors
Vagus causing secretions for prolonged periods
Intestinal- response to duodenal stretch and reduced pH in duodenum
I cells- CCK and S- Secretin causing decrease in secretions
But can be stimulated if there’s long peptides in chyme
Sphincters of small intestine
Pyloric sphincter
Ileocaecal valve
Sections of small intestine and function
Duodenum- 0.25m- contians submucosal glands that neutralise acidic chyme
Jejenum- 2.5m- large submucosal folds- plicae circularis- larger than rest of SI folds
Ileum- 3.75m- many peyers patches
Features in small intestine
Villi
Crypts of liebemkuhn
Cells of the small intestine
Enterocytes- tall columnar with microvilli, glycocalyx traps mucus and enzymes
Goblet- used to hydrate contents since a lot is being
absorbed, therefore increase in number further down
Enteroendocrine-G Gastrin,I CCK,S Secretin,D somatostatin
Paneth- immunological cell, near bottom of crypts, contain lysozyme
Motility of small intestine
Peristalsis- aids movement of substances further down GI tract
Segmentation- aids mixing- with enzymes
Migrating motor complex- periodic contractions from stomach to distal end of ileum, during fasted state, in order to cleanse SI of residue food
Digestion and absorption of Carbohydrates
Salivary amylase- breaks down polysaccharides
Pancreatic amylase- also breaks them down to disaccharides
Sucrase, maltase and lactase in small intestine breaks them down to monosaccharides- located one brush border
Glucose and galactose absorbed via secondary active transport by SGLT1 on apical
Fructose absorbed via facilitated diffusion by GLUT5 on apical
All 3 absorbed by facilitated diffusion by GLUT2 on basal
Digestion of Protein
Parietal cells produce HCl which activates pepsin, which breaks down proteins into polypeptides
Pancreas produces Trypsinogen, procarboxypeptidase, chymotrypsinogen. Trypsinogen is activated to trypsin by enterokinase which is produced by duodenal cells. Trypsin further activates the other zymogens to carboxypeptidase and chymotrypsin which breakdown the polypeptides to di/tripeptides
Carboxypeptidase, endopeptidase, dipeptidase and aminopeptidase are located in the brush border which digest to amino acids
Absorption of peptides
Single amino acids are absorbed by secondary active transport via AA/Na symporter
Di/tripeptides can also be transported in via this mechanism
AA are them absorbed by facilitated diffusion on basal membrane but peptides cannot and have to be broken down by cytoplasmic peptidase enzymes first
Digestion of lipids
Linguinal and gastric lipase start to digest triglycerides
Churning of stomach starts to emulsify
Bile enters duodenum and emulsifies fats
Pancreatic lipase breakdown TAG to MAG and fatty acids
Absorption of lipid products
Combine with bile salts at brush border- which transport them across aqueous unstirred layer overlying enterocytes
Then lipid products are absorbed, bile salts stay in lumen and get absorbed in terminal ileum
TAG resynthesised via 2 pathways- monoglyceride acylation or phosphatidic
Packaged into chylomicrons- lymphatics- villis lacteals
5 parts of pancreas
Uncinate process, head, neck, body, tail
Pancreas’s ducts enter duodenum at
Join with common bile duct at ampulla of vater
Controlled by sphincter of oddi
Drainage of pancreas
Hepatic portal vein
Cells of the pancreas
Acinar cells- secrete zymogens (if active would degrade tissue), active lipase and amylase in granules. At end of duct, secreting viscous, enzyme rich fluid
Duct cells- line duct cells, secrete watery, dilute bicarbonate into pancreatic fluid
Islet of endocrine tissue- beta (70%), alpha (20%), delta (10%)
Centroacinar cells- function like duct cells
Mechanism of duct cell secretion
Co2 diffuses in allowing production of bicarbonate and H+
Na from interstitum moves paracellularly to the duct lumen which water follows, creating watery secretion
Bicarbonate is secreted into duct lumen via secondary active transport, since Cl- are actively transported out into the lumen then bicarbonate is exchanged with Cl-
There will be accumulation of H+ in the cell which needs to be removed- done via secondary active transport
Na+ is pumped out via Na/K pump, then Na is exchanged for H+, and K+ can move out cell via channel
Duct cells vs Parietal cells
Duct cells pump bicarbonate into lumen and protons into interstitial
Parietal pump H+ into lumen and bicarbonate into interstitial
Control of Trypsin
And when this goes wrong
Inhibitor is also secreted by pancreas
Gallstones blocking can cause a build up of enzymes in pancreas, causing trypsinogen to convert in absence of EK, causing pancreas auto-digestion and pancreatitis
Hormonal Control of bicarbonate
Low pH in duodenal wall, activates S cell to produce Secretin, this goes into the blood to the pancreas
Binds to basolateral receptors on duct cells, increase cAMP and activates Cl- channels on apical causing more bicarbonate being bicarbonate moving into lumen
Hormonal effect on enzymatic secretion
Mixed meal detected in duodenum by I cells which secrete CCK(cholecystokinin) which binds to CCK1 receptor on acinar cells activating PLC causing exocytosis of granules into duct
Nervous stimulation of enzyme secretion
Vagus secretes Ach, causing increased IP3 and Ca2+, causing increased granules exocytosis
Phases of pancreatic secretion
Cephalic and gastric- innervated by vagus nerve
Intestinal phase- hormal main innervator
This has negative feedback loop since hormones cause pH to rise which then stops hormone production
Hormonal signal interaction
CCK no real affect on bile secretion alone
Secretin has an increased affect alone
But together massive amplification- CCK interacts with signals of duct cells
Secretin has no affect on CCK mediated release of acinar cells
Liver functions
Catabolic and metabolic
Bile secretion and removal of waste
Detoxification and immunological
Bile fucntion
Emulsify fast
Cholesterol homeostasis
Toxin excretion (endogenous- bilirubin and exogenous-drugs)
Anatomy and blood supply of liver
Hepatic portal vein and hepatic artery supply
3 Small hepatic veins drain- left, right and middle
2 main lobes, 9 segments (independent)
Hepatic lobule
Made up mainly of hepatocytes
In a hexagonal structure
Portal triad and hepatic acinus
3 hepatic lobules share a branch of the hepatic portal vein, hepatic artery and bile duct
Acinus is the functional part of the liver- is 2 adjacent 1/6th of lobules that share 2 portal triads
Portal veins splits into in the liver
Sinusoids, which have no basement membrane, fenestrated, discontinuous endothelium
Making them very leaky
Cells of the liver
Kuppfer cells- adhere to endothelium, sinusoidal macrophages- stellate shapes
Hepatic stellate cell-perisinosoidal cell that stores Vitamin A, activates and populates during disease(acts as fibroblast)
Hepatocyte- cuboidal and receive nutrients from sinusoids-synthesise albumin, bile salts, clotting factors
Cholangiocyte- biliary epithelial, secretes bicarbonate and water- which combine to form bile
Also reabsorb sugars and acids
Biliary Tree
Bile canaliculi next to hepatocytes
Drain to small ductules which go to small bile ducts
Which drain to large bile ducts of each segment
Merge as R and L hepatic duct- common hepatic duct
Primary salts
Cholic acid
Chenodeocycolic acid
95% absorbed in terminal ileum
Secondary salts
Gut bacteria convert salts to
Deoxycholic acid
Lithocholic acid
Enteroheptic Circulation
Cycle between liver and gut, via the hepatic portal vein and the bile duct
Cycle increases half life of drugs
Gluconeogenesis
Deamination of amino acids- alanine- pyruvate- glucose
Breaking down triglycerides- Triglyceride-glycerol- glucose
Cori cycle- use of 6 ATP to convert lactate to glucose
Lactate- delivered to liver from muscles via blood, then converted to glucose which is then transported from hepatocytes via veins
Protein Metabolism in liver
Transamination- switching of amino groups and keto acid
- liver can produce key aa
- Glutamate is a key common intermediate
Deamination- removal of amine group from aa, replaced by keto group to form keto acid
Muscles liberate alanine via transamination
Converted to glutamic acid in the liver- which is deaminated to pyruvate and converted to glucose and transported to muscles
Fat metabolism in liver
When glycerol storages are full- excess aa and sugars converted to fats- stored as triglycerides in adipose tissue
Ketone body synthesis- Acetyl CoA is formed and used to make acetoacetate and 3-hydroxybutyrate which are used by other tissues via thiophorase enzyme (not located in liver)
Lipoprotein Synthesis
Liver synthesises phospholipids, cholesterol and lipoproteins
Lipoproteins carry varying amounts of triglycerides
Other functions of liver
Store lipid soluble vitamins
Protection via kupffer cells
Ca2+ metabolism
Iron stores- ready for erythropoiesis
Embryology of foregut
Days 29-34- liver bud from foregut endoderm
Day 35-39- Pancreas starts developing in 2 places as dorsal and ventral pancreatic bud. Duodenum distinguishable from stomach
Day 40-55- Liver starts to shape, gallbladder and bile duct distinguishable, duodenum starts to twist to move pancreatic ventral bud to dorsal bud
Day 56- Ventral and dorsal buds fuse, and these fuse with bile duct
Calcium absorption
Occurs in duodenum and ileum
Absorbed by ion channel and Intestinal calcium binding protein (IMcal)- facilitated diffusion
Calcium binds to calbindin- since we need to keep intracellular calcium low as it is a signal molecule
It is then removed from the cell via PMCA(plasma membrane Ca ATPase)- high affinity, low capacity
and Na/Ca exchanger- low affinity, high capacity
Why is iron important
Oxygen transport and oxidative phosphorylation
Absorption of iron
Is present in diet as Fe2+, Fe3+ and as heme groups
Heme is absorbed by HCP-1 via receptor endocytosis
Fe2+ then liberated
Fe3+ converted to Fe2+ on brush border via Duodenal cytochrome B
Fe2+ is absorbed by divalent metal transporter 1(DMT-1), H+ symporter
Moved to basolateral membrane and into blood via ferroportin
Hephaestin- converts Fe2+ to Fe 3+- which binds to apotransferin and travels around as transferrin
Importance of Vitamin D
When absorbed, it increases calbindin and PMCA, increasing calcium absorption
Regulation of Iron absoprtion
Hepcidin suppresses ferroportin preventing iron absorption in the blood
In excess iron absoption
Fe2+ binds with apoferritin to form ferritin micelle
Fe2+ is converted to Fe 3+ which crystallises the shell
Vitamin B12 absorption
Liver has a large store of VItB12
In stomach the digestion od peptides releases B12
This binds to R protein formed in the salivary glands and parietal cells to prevents denaturation
R protein digested in the duodenum, Intrinsic Factor secreted in the stomach will bind after R proteins release B12
B12-IF complex resistant to digestion, complex binds to cubilin receptor and is taken up in distal ileum(possibly receptor endocytosis)
Complex broken down in mitochondria and B12 binds to transcobalamin II(TCII)- then secreted into blood and absorbed by liver by TCII receptor, and then TCII is broken down by proteolysis
Nervous innervation of the gut
Myenteric plexus- located between circular and longitudinal muscle, control of motility
Submucosal Plexus- afferent senses lumen environment- chemo, mechano and Osmoreceptors
Efferent- fine tunes blood flow and secretions
Function of Enteric innervation
Absorption
Secretion
Perfusion
Motility
Sympathetic innervation
Splanchnic Nerves arising from thoracic and lumbar regions
Thoracic- foregut, midgut and other associated organs
Lumbar- Hindgut
Inhibits GI activity
Direct effect of blood flow
Parasymphathetic innervation
Vagus nerve (CNX) innervates most of the GI tact and pelvic splanchnic nerve innervates the hindgut
Activates GI activity
Neurotransmitters of autonomic nervous system to GI tract
Symp- NA
Para- Ach
Pathway and response for GI tract
Chemo and mechanoreceptors detect change- this has a local afferent to enteric plexus
But also has splanchnic and vagus afferent effect to CNS which can then have an efferent effect and fine tune enteric NS
Paracrine regulation in GI tract
Somatostatin produced by d cells (type of enteroendocrine cell) inhibits HCl secretion by parietal cells
Histamine produced by Enterochromoffin like cells stimulate parietal cells to produce acid
Endocrine regulation in GI tract
Somatostatin- inhibits histamine, gastrin production and gut motility
Secretin- S cells stimulated by low pH in duodenum, and causes bicarbonate production. High levels inhibit HCl and gastric emptying
Cholecystkinin- I cells detect small peptides and lipids and increases pancreatic enzyme release, reduces gastric emptying, reduces appetite and gall bladder contraction
Gastrin-stimulated by peptide presence, vagal innervation and gastric distention- causes HCl release
Gastric Inhibitory Polypeptide- secreted by K cells in duodenum and jejenum- upregulates insulin and at high level inhibits stomach functions
Appetite-neural pathway
Hypothalamus controls appetite(incomplete blood brain barrier)- contains arcuate nucleus and paraventricular nucleus
Arcuate nucleus has 2 nuclei- Agrp/NPY and POMC
NPY/Agrp neurones secrete Agrp to paraventricular nucleus which inhibit MC4R and stimulate food intake behaviour
POMC secretes alphaMSH to paraventricular nucleus and activates MC4R which inhibits food intake behaviours
Leptin mechanism
Made in adipose white tissue
Amount in circulation proportional to amount of fat you have
Acts on hypothalamus to reduce food intake
However obese people are probably resistant to it due to such high amounts
Other hormones regulating appetite
Peptide YY
Ghrelin
Peptide YY mechanism
After eating, it is released from the small intestines
Amount released proportional to calorie intake
Inhibits NPY release and sitmulates POMC release
Causing a decrease in appetite
36aa
Ghrelin Mechanism
Structure- fatty acid bound to peptide- released from the stomach
Increases before meal
Directly modulates neurones in arcuate nuclei
Stimuates NPY/Agrp neurones and inhibits POMC
Increases appetite
Levels decrease after a meal
Control of hydration
Osmoreceptors have their cell bodies located outside the blood brain barrier detect change and send signal to hypothalamus
Increased firing increases vasopressin produced and released in the posterior pituitary gland and cause water reabsorption
Control of thirst
Presence of water in GI tratc can suppress thirst for short period of time due to receptors in upper GI tract
Thirst only goes away once change has been accounted for
Hormonal control involves ANGII, aldosterone and ADH
Parts of the large intestine
Caecum, appendix, ascending colon, transverse colon, descending colon, sigmoid colon, rectum and anal canal
Blood supple of large intestine
Superior mesenteric- right, middle and ileocolic artery
Inferior mesenteric- left, sigmoidal, superior rectal
Large intestine function
Water and electrolyte absorption, bacteria environment and elimination of waster
Has capacity to absorb 4500ml/day, over this results in diarrhoea
Features of large intestine
Appendices epiploicae
Taenia Coli- 3 bands of longitudinal muscle
Circular muscle is segmentally thickened and is irregularly intervened by taenia coli
Haustra- pouches formed by Taenia coli being shorter than the intestine
Anal Sphincters
Internal anal sphincter- smooth muscle under self control
External anal sphincter- striated muscle under voluntary control by pudendal nerves
Cells of large intestine
Enterocytes- short irregular microvilli
Goblet cells- dominate crypts and hydrate contents
Many invagination with stem cells in the pits which move up and replace
Glycocalyx present but no digestive enzymes in brush border
Motility in large intestine
Basic contraction- kneading process that moves the content 15cm/hr, allowing chyme to stay in colon for a long time. In transverse and descending, there is haustral contractions (of circular muscle) moving content
Mass movement-1-3 times a day, propels contents majority of colon. Fibre(indigestible carbs) promote this
Large peristaltic movements
Defaecation
Usually after mass movement faeces store in the rectum on the shelves. The distention causes contraction of descending sigmoid colon and rectum, and inhibit the internal anal sphincters. But conscious control is needed to relax the external
Function of gut bacteria
Synthesis and exertion of vitamin K
Prevent pathological bacteria colonising
Stimulate production of cross reactive antibodies
Stimulate certain tissue growth
GI mucosa protection
Physical barrier- tight junctions, mucous
Chemical- acid, bacteriacidal enzymes from paneth cells
Bacteria
Immunological- GALT (Organised: Peyer’s patch, mesenteric lymph nodes, Disorganised: lymphocytes in lamina propria and interstitial space) and MALT- oral cavity
M cells
Follicle associated epithelium- overlies PP
Form tight junctions
Reduced glyocalyx
Lacks lysosomes so doesn’t alter antigenic properties
MHC II
Immunological structures
Follicle associated epithelium
Sub epithelial dome underlying- contains B cells DC, T cells and macrophages
M cells pass antigens to SED
Peyers patch underneath
Antibody response
IgA main AB produced at mucosa surface- stimulated by m cells
Dimer secreted to basal end on epithelium and then binds to PolyIg receptor and is endocytose
It then combines with secretory component to become secretory IgA
Lymphocyte circulation
Axticated in PP, travel to mesenteric lymph node and then circulation
Endothlial express adhesion molecules and allow lymphocyte homing
Area of inflammation will secrete MADCAM-1 on its HEV which binds to L selectin
Immunological disorder of gut
Coeliac disease
Irritable bowel syndrome
Crohns disease
Ulcerative colitis
Irritable bowel syndrome and treatment
Recurrent abdominal pain
Abnormal bowel motility - constapation and diarrhoea
Visceral hypersensitivity
Treatment- simple carbs
- fibre for constapation
Coeliac disease
Autoimmune disorder where gluten causes attacks on own cells in small intestine
Gladin in gluten causes the attack
Symptoms in children- abdominal distention, diarrhoea
In adults- chronic diarrhoea, bloating
Eat gluten free
Crohn’s Disease and treatment
Causes inflammation anywhere along GI tract
Uncrontrolled immune response damaging GI tract
Symptoms- diarrhoea, blood in stools, pain and if SI affected malabsorption
Treatment: Antibiotics- underlying bacteria cause e.g Listeria Anti-inflammatory Immunosuppresants Surgical removal - doesn't cure
Ulcerative colitis and treatment
Restricted to colon
Causes ulcer formation(tissue erodes- open sore)
Autoimmune
High productive sulphide producing bacteria
Symotoms- diarrhoea and blood in stool and pain
Treatment- anti-inflammatory
Immunosuppresants
Colectomy- cures
Gut infections
Cholera- watery diarrhoea
Rotavirus
Norovirus- acute gastroenteritis
Campylobacter- food poisoning
E. coli- ETEC diarrhoea and EHEC- kidney failure
Clostridium Difficile- high reoccurrence rate
Malnutrition
Over nutrition and under nutrition
25Kcal/Kg
Vitamin C roles and deficiency
Converts Fe3+ to Fe2+
Important in collagen formation
Deficiency can result in scurvy
What confounds body weight monitoring
Fluid contents
In cases of malnutrition body weight can confound due to peripheral oedema
Mechanism in undernutrition
Ketones supply the brain
Amino acids from muscle convert to glucose
Body starts to undergo energy conserving measures
Signs of undernutrition
Weight loss Muscle wasting Peripheral oedema Chronic infections Hair loss Glossitis- cracking at mouth
Types of malnutritions
Kwashiorkor- protein deficiency causing periphery oedema, growth failure
Maramus- prolonged starvation, growth failure, no oedema
Beri Beri disease- deficiency of thiamine (VitB1) , required on nerve cells membrane, resting in lethargy
Pellagra disease- deficiency in niacin (VitB3) which is required in NAD and NADP, resulting in diarrhoea and inflamed skin
Bilirubin Pathway
Mainly made in spleen as a result of haemoglobin breakdown
It is then secreted into the blood where it bounds to albumin
Dissociates in the liver and and free bilirubin enters- binds to 2 UDPGA(glucoronic acid) to form conjugated bilirubin (digulcoronide bilirubin) - more soluble than free
This is then excreted in bile ( some passes to general circulation)
GIT bacteria convert BR to urobilinogens
GI mucosa is permeable to unconjugated BR and urobilinogens but not conjugated BR
Some urobilinogens reabsorbed and enter enterohepatic cycle and some are then excreted in kidney
Urobilinogens not reabsorbed can be converted to stercobilinogens which are passed in the stools
Problems arising from bile flow
Cholestasis- cessation of bile flow
Jaundice- excess bilirubin in the blood
Causes of jaundice
Pre-hepatic- increased bilirubin production, haemolysis, ineffective erythropoiesis, massive transfusion- so more in blood
Hepatic- hepatocytes not working and struggle to conjugate- doesn’t enter bile as quick and accumulates in blood
Post hepatic- physical problems in bile duct- more passes in circulation and body tries to excrete as much bilirubin in urine, but pale stool
Gilberts Syndrome- reduced activity of UDPGT, so less conjugated bilirubin forms and more accumulates in the blood
Liver failure consequences
Hypoglycaemia
Coagulation and bleeding
Increased susceptibility to infection
No detoxification- encephalopathy and cerebral oedema
Cause and treatment of acute liver failure
Common cause- paracetamol overdose, and chronic alcoholics
Treatment- transplant
Oesophageal cancer
Squamous- upper 2/3
Adenocarcinoma- metaplasia- columnar cells (baretts precursor), lower 1/3
Symptoms of colon cancer
Usually asymptomatic
But can cause change in bowel habits and blood in stools
Best investigation of colon cancer
Colonoscopy – safe, quick, sensitive, you can obtain tissue but requires bowel prep (dehydration risk)
CT virtual colonoscopy – quick, easy, reduced bowel prep, as good as colonoscopy – but no tissue
Pancreatic cancer
Usually asymptomatic
But can cause- weight loss, anorexia and pain
Early symptoms: abdominal pain, depression, glucose intolerance.
Later symptoms: weight loss, jaundice, ascites, obstructed gall bladder.
Poor outcome- 1 yr survival 18%, 5 year 2%
Acute Pancreatitis and signs
An acute inflammatory process that leads to necrosis of the pancreatic parenchyma
Signs and symptoms include severe abdominal pain, nausea, vomiting, diarrhoea, fever, and shock
Diagnosing pancreatitis
BLOOD TESTS COMPLEX BLOOD TEST SIMPLE IMAGING CROSS SECTIONAL IMAGING INVASIVE TEST
Complications of pancreatitis
Local- necrosis, fluid accumulation, chronic pancreatitis
Systemic- hypovolaemia , hypoxia, hypoclacemia, hyperglycaemia
Chronic pancreatitis
A progressive fibroinflammatory process of the pancreas that results in permanent structural damage, which leads to impairment of exocrine and endocrine function.
Chronic pancreatitis symptoms
Malabsorption
Loss of 90% exocrine function
Fat soluble vitamin (A, D, E and K) malabsorption
Steatorrhea
Chronic pancreatitis management
Stop drinking and smking
Small meals with low fat
Pancreatic supplements and proton pump inhibitors
Obesity and its risks
BMI>30
Obesity is associated with many comorbidities including depression, ischaemic heart disease, gallstones, cancers, infertility, stroke, sleep apnoea, hypertension, diabetes, osteoarthritis, gout.
Risk of diabetes from body structure
If stores more body fat around waist for a given BMi, increased risk of diabetes
How has diet changed
Food has become cheap
Energy density of food increased
Increased processing of food
NICE guidelines to obesity
Diet, exercise, behavioural therapy, drug treatment, surge
Gall bladder epithelium modify bile when stored
Reabsorb electrolytes and water, concentrate the acids
This generates a more concentrated bile
