GI Flashcards
What are the functions of the stomach?
To store and mix food, dissolve and continue digestion, kill microbes, regulate flow of food, secrete proeases, secrete intrinsic factor, Lubrication.
Where is B12 absorbed?
Terminal ilium
What is chyme?
chewed up food that leaves the stomach.
What are the areas of the stomach?
cardia where the oesophagus joins, fundus at the top, body main top bit, antrum bottom main and pylorus the bit near the sphincter.
What are the key cells of the stomach?
Mucous cells, parietal cells, chief cells and enteroendocrine cells
Where are most of the mucous cells?
On the surface of the wall lining.
What are gastric pits?
The dips in the surface of the stomach. where you get parietal chief and enteroendocrine.
Where are you most likely to find parietal cells?
In the pits of the fundus and body not antrum
Where are you most likely to find chief cells?
In the pits of the antrum
What is Gastric acid?
Hydrochloric acid, about 2 litres a day, more than 150nM H+ concentration
Which cells produce gastric acid?
Parietal cells
How is gastric acid produced?
Chloride diffuses into the stomach passively to keep it electrically neutral by having potassium leaving. To increase H+ there is a hydrogen potassium pump ATP is used here. the comes from water. to replenish hydrogen ions carbonic andydrase converts CO2 into carbonic acid and the bicarbonate is released and the let into the blood by swapping with a chloride
What is an effect of vomiting ?
Low potassium
What is the turning on cephalic phase?
Initiated by the parasympathetic nervous system. this happens when we see smell or taste food. it causes Acetylcholine to be released onto parietal cells and triggers the release of gastrin and histamine which increases acid production
What is the gastric phase turning it on?
Gastric distension and the presence of pepties and amino acids stimulates release of gastrin, and this acts on parietal cells. Gastrin triggers the release of histamine which also acts on parietal cells which increase acid production
Why is histamine important?
It acts directly on parietal cells but also mediates the effects of gastrin and acetylcholine. which make this a good target for drugs
Why does protein in the stomach initiate acid release?
It is a direct stimulus for gastrin release, the protein acts as a buffer increasing pH by absorbing H+ ions, this leads to decreased somatostatin and more parietal cell activity
How is gastric acid secretion reduces in the gastric phase?
Low pH directly inhibits gastrin selection, it indirectly inhibits histamine release via gastrin and stimulates somatostatin release which inhibits parietal cell activity
How is gastric acid secretion turned off in the intestinal phase?
Distension in the duodenum, low luminal pH, hypertonic luminal contents and presenece of amino acids and fatty acids, these lead to enterogastrones being released such as secretin, which inhibits gastrin release and promotes somatostatin, it also releases choecystokinin and reduces ACh release
What type of signalling cells are gastrin, acetylcholine, histamine and somato statin?
Gastrin is a hormone, Histamin and somatostatin are paracrine chemicals, Acetylcholine is a neurotransmitter
How do the chemical act on the parietal cells?
Causes the more of the pumps to be put on the surface of the cells
What are peptic ulcers?
an ulcer is a breach in a mucosal surface.
What are the causes of peptic ulcers?
Helicobacter pylori infection, Drugs-NSAIDS, Chemical irritants alcohol and bile salts, dietary factors and gastrinoma.
What are the mechanisms of peptic ulcers?
Too much acid, or weakened mucosal defence
How is the stomach lining protected from the acid it produces?
Alkaline mucus, tight junctions between epithelial cells, replacement of damaged cells and feedback loops
How can helicobacter pylori cause an ulcer?
They live in the mucus, secreat urease splitting urea into ammonia and this can bind to hydrogen ions and proteases phospholipases and vacuolating cytotoxin A can damage the gastric epithelium and cause an inflamatory response which reduces mucus production
What are NSAIDs responsible for in the stomach?
Mucus secretion is stimulated by prostaglandins and Cyclo-oxygenase 1 needed for the synthesis of this, NSAIDS inhibit cyco-oxygenases and this reduces the mucosal defence
How can bile salts case ulcers?
Duodeno-gastric refux, regurgitated bile strips away mucus layer, reduce mucosal defence
How can Helicobacter pylori induced ulcers be treated?
Proton pump inhibitor for the acids, and two types of antibiotic to reduce numebrs of bateria
How can NSAID ulcers be treated?
Give the a proton pump inhibitor or histamine blocker, give them a prostaglandin analogue
Which cells secrete intrinsic factor?
Parietal cells
Which cells produce pepsin?
None
Which cell produces pepsinogen?
The chief cells
What is a zymogen?
An inactive form of an enzyme
What stimulates chief cells?
Same as for gastric acid
What activates pepsinogen?
Hydrochloric acid and pepsin can make it into pepsin
How is pepsinogen modified into pepsin?
it is cleaved into smaller parts
What allows for protease activation?
Low pH
How can pepsin be inactivated?
By reacting with the HCO3 in the small intestine
How much of protein digestion is the stomach responsible for?
abour 20%
What is the role of pepsin?
Not essential but accelerates protein digestion. Breaks collagen in meat
What is the volume of the stomach?
50mL
What is the maximum volume of the stomach?
1.5L
What is receptive relaxation?
Passive relaxation of the muscularis propria to increase the volume of the stomach
What helps gastric receptive relaxation?
Vagus parasympathetic innervation. NO and seretonin and enteric nerve plexuses
What is peristalsis?
Rhythmic wave like contractions in the walls of the stomach.
What are the pacemakers of the stomach?
Interstitial cells of khal also in intestines
Describe the contraction of the stomach?
Weak in fundus and body. forces food to pylorus and it closes the sphincter and squeezes food against it.
How is food let out of the stomach?
Small letting out of chyme into duodenum
How frequent is the basic electrical rhythm?
3 times per minute
How are gastricdepolarisations transmitted to other cells?
through gap junctions
How are the pacemakers able to generate action potentials?
ACh stimulus and other hormones to stimulate an action potential gastrin can do it and mechano receptors release gastrin
What duodenal factors decrease gastric motility?
increased duodenal luminal fat duodenal distension, duodenal osmolarity, decreased luminal pH
What is the importance of controlling gastric emptying?
The capacity of the duodenum is less than the capacity of the stomach
What is dumping syndrome?
When too much hypertonic solution goes into the duodenum.
What are the symptoms of dumping syndrome?
Vomiting, bloating, cramps, diarrhoes, dizziness, fatigue, weakness, sweating, dizziness, tachycardia
What is gastroparesis and its causes?
Delayed gastric emptying, no known cause, can be autonomic neuropathies, drugs, abdominal sugeries, parkinsons, MS scleroderma, amyloidosi, Female gender
What drugs can cause gastroparesis?
GI agents H2 antagonists, proton pump inhibitors, Anti cholinergic medications, Dephenhydramine, Opiod analgesics, Tricyclic antidepressants
Others Beta adregenergic agonits, calcium channek blockers, interfereon alpha
What are symptoms of gastroparesis?
Nausea, early satiety, comiting undigested food, GORD, Abdominal pain, Bloating anorexia
What is special about the circulation in the liver?
There is the normal blood supply from the hepatic artery and blood returns to the heart by the hepatic veins and the IVC. Blood also comes from the small intestine via the superior and inferior mesenteric vein.
What are some of the main functions of the liver?
Detoxification- Filters and cleans blood of waste products
Immune functions- fights infections and diseases
Synthesis- of clotting factors proteins enzymes, glycogen and fats
Production of bile- and breakdown of biirubin
Energy storage- glycogen and fat
Regulation of fat metabolism
Ability to regenerate
Describe the metabolic role of the liver
Continuous supply of energy for the body by controlling the metabolism of carbohydrates and fats
What regulates the liver metabolic activity?
Nerves and endocrine glands like the pancreas thyroid and adrenal glands
Where are lipides stored?
in adipocytes in hepatocytes and elsewhere
Which are more fluid saturated or unsaturated fatty acids?
Unsaturaes as they need more space due to their bent shape
What are the functions of lipids?
Part of cell membranes, Energy reserve, Integral to form cells, can be part of inflamatory cascades(arachadonic acid)
Hormone metabolism like sx hormones and vitamin D
Where does energy in the body come from?
The oxidation of lipids or carbohydrates. 30-40 days of lipid energy lipid reserve 100000kcal
Where is the main storage f glycogen?
In the liver
Where do lipids come from to the liver?
The portal vein hepatic artery and lymphatics
In what form are lipids brought into the liver?
As free fatty acids
How can fatty acid storage be increased?
Eat more fatty acids.
How are lipids transported in the body?
As tryglycerides or fatty acids bound to albumin or within lipoproteins. Triglycerides cant pass through membranes by fatty acids can
What are the ways that fatty acids can be taken up by the liver?
Fatty acid binding proteins, Fatty acid translocase and fatty acid transport polypeptide
What is the name of the enzyme that can convert triglycerides into free fatty acids?
Lipoprotein lipase
What enzyme releases fatty acids from adipocytes?
Hormone sensitive lipase
What does insulin do in terms of fat storage?
Fat storage in adipocytes, stimulates lipoprotein lipase to break down TG to release FFA to be stored in the adipocytes. it reduces the activity of HSL so there is reduced export of lipids from the adipocytes
What are the effects of insulin resistance on fats?
Increased lipolysis in adipocytes leading to lots of TG in circulation, Increased offer of fatty acids to the liver so their uptake increases. increased glucose levels in blood mean less demand for lipids so used to store energy.
What is de novo lipogenesis?
Happens in the liver and is the sequential extension of an alkaoic chain starting from Acetyl-CoA via seria decarboxylative condensation reactions.
What is the rate limiting step of de novo lipogenesis?
Aecetyl-CoA to Malonyl-CoA catalysed by Acetyl-CoA carboxylase
What affects the rate of de novo lipogenesis?
Rate is related to Fatty acid sythetase which is activated by insulin and inactivated by catecholamines and glucagon, it has negative feedback on itself
What are lipoproteins?
A core of triglycerides and cholesterol-esters and a surface monolayer of phospholipids colesteral and specific proteins(apoproteins)
What determines the type of lipoprotein?
the ratio of protein to lipid defined by their density LDL HDL VLDL and chylomicrons
What do chylomicrons do?
Carry lipids from the gut to muscle and adipose tissue
What happens to chylomicron remnants?
They are taken up in the liver
What percentage of cholesterol comes from food?
10%
Where is cholesterol processed?
In the liver
How is cholesterol excreted?
Through the bile. it taken by lipoproteins in the circulation to the liver
How is fats and cholesterol exported from the liver?
As bile acids and VLDL
What is the process to export a fatty acid?
Apoprotein B100 is synthesised in the rER the lipid compnent is synthesised in the sER they are atted by TAG proteinsto ApoB. They are sent to the Golgi apparatus where ApoB is glycoosylated and then migrates to the sinusoidal membrane and exocytosed as a VLDL
What affects Fatty acid oxidation?
Periperal fatty acid availablility increased by glucagon and decreased by insulin.
What are the 3 locations for oxidation of fatty acids in the liver?
Peroxysomal Beta oxidation
Mitochondrial beta oxidation and ER omega oxidation CYP4a catalysed
What is mitochondrial beta oxidation?
Multistep progressive reduction in chain length which leads to ketone bodies. It is regulated CPT carnitine palmitosyl transferase and carnitine concentration and malonyla CoA which inhibist CPT. genetic disorders can affect it and alcohol
What is peroxisomal beta oxidation?
Main role is detoxification of
very long chains, 2 methyl branched FA, dicarbolic acid which inhibit mitochondira, prostanoids, C-27 bile acid intermediaroes
It is 4 step and each step can be done by 2 enzymes,. if it goes wrond leats to microvesicular steatosis
What is steatosis?
Fat gathering in the liver cells
What is microsomal omega oxidation?
Important in overload, CYP4A enzyes oxidise saturated and unsaturated fatty acids, hydroxylation in ER folloed by decarboxylation to enter beta oxuadation.
How are Fatty acids able to regulate actions?
Gene expresson by controlling transcription factors. the control metabolic machinary for metabolic machinery for fatty acid metabolism
What are PPAR?
Receptors for lipids, all involved in lipid homeostasis, only gamma is energy storage alpha is gene transcription
What happens in defective metabolism?
Less oxidation(or is overloaded) microsomal oxidation increases causein more dicarboxyl acids which inhibit other pathways ofoxidation and leat to lipotoxicity and steatohepatitis
What are the deaseases reated to fat in the liver?
NAFLD non-alcoholic fattty liver diseas and NASH non-alcoholic steatohepatitis.
What are the stages of liver damage?
Fatty liver (deposits of fat cause enlargement), liver fibrosis (scar tissue forms) and cirrhosis ( growth of connective tissue destroys liver structure .
What causes fatty liver?
Increased TG in plasma from excess diarary intake and caloric intake. Also increased flux of FA increase releae of FA and uptake by hepatocytes. Decreased FA oxidation which decreased demand for lipids and increases storage.
What is steathepatitis?
Too much fat in the liver. Leads to large release of TG and FA overload increase Reactive Oxygen species production, It causes inflamation from kupffercells ad ethanol can activate stellate cells for fibrogeneseis. lipidperoxidation products cause inflamation
How do you manage fatty liver diseas?
Reduce calories, increase demant for consumption. usually will burn the fat off
How does alcohol cause fatty liver?
The high calorific values cause fat storage.
How does alcochol get procesed?
Increases loads PPAR aloha is inhibited and so is fat oxidation and FAS increases lipogenesis. causes dammge to organells and causes fibrosis
Which of the layers in the trilamina disk form the mid and hind gut?
Endoderm forms the mucosa of the bowl some layers are from mesoderm
What types of folding happens in the embryo?
Lateral the mesoderm and endoderm come round to make boweltube and is surrunded by the mesoderm to form the mesentry and peritoneal membrane
What deos the endoderm give rise to in the GI tract?
The endothelium of the bowel the hepatocytes of the liver and exo and endocrine pancreas
What does the visceral mesoderm give rise to?
The muscular wall connective tissue and cisceral peritonium
What is interesting about innervation of perietial peritonium?
It is the same as the overlying skin
What is interesting about innervation of visceral peritoneum?
It is supplied by separate nerves the greater for foregut lesser for mid and least for hind and causes refered pain
Where do the lungs develop from?
The foregut
Where is the boundary of the foregut and midgut?
Where the pancreatic duct joins the bowel.
What is the first stage of the GI developmen?
There is a forward looping supplied by the superior mesenteric artery
Where is refered pain for the heart and lungs?
T1-T5 inside of forarm and upper arm and on chest
Where is referred pain for the Foregut?
T5-T9 below nipples and umbilicus
Where is referred pain for the midgut?
T10-T11 the umbilicus
Where is referred pain for the Hindgut?
T12 just above hair bearing area
Describe the stages of the tube?
Elongation, physiological herniation, rotation, retraction and fixation
What happens in elongation and herniation?
it elongates and then most of midgut loop passes through the umbilicus. elongates in the cephalic limb close to the head. it has rapid growth while the liver and pancreas grows in week 6
Describe the rotation of the tube?
the caecum rotates infront of the bowl clockwise from above to put it in the right lower part.
Describe retraction?
the abdominal area is big enough the mesentry facilitates this as it doesnt extend/ the transverse colon and the duodenum comes in first.
Where is the appendix?
In a variable position which leads to variable presentation of diseases.
What is the fixation stage?
on organs that are retroperitoneal the two layers fuse together and fix it to the wall
Which parts of the GI tract are fixed?
The duodenum apart from very first part. Ascending colon and descending and rectum
Where is the mesentry for the transverse colon passing?
Above the duodenum and across.
Where is the small intestine mesentry running from?
The duodena jejunal flecture to the illio cecal valve.
How can you look at the bowel?
Barium ennema and pump air in to xray it.
What embryological faults can happen?
retraction- part of bowl in the umbilical cord or can rupture the cord.
rotation- caecum not in right place
What is the function of saliva?
Lubricant for mastication, swallowing and speech
Oral hygiene to wash the mouth buffer the acidity, and offer immune defence
Adds digestive enzyme and aids taste and without it can lead to infection and pain
What is the flow rate of saliva?
0.3-7ml per minute arount 1-1.5L over a day
What is the pH of saliva?
6.2-7.4
What is in the saliva?
Water serous secretion of amylase alpha and mucus secretion other enzymes such as water etc
Which salivary gland only produces serous secretions?
Parotid gland
What factors affect the composition of the saliva?
Flow rate, circadian rhythm, type and size of gland, duration and type of stimulus, diet, drugs, age ,gender
What defenses are there in the mouth?
The mucous provides a physical barrier. the palatie tonsils that have lymohocutes and dendritic cells, salivary glands wash away food and bacteria
Which glands continuously produce saliva?
Submandibular, sublingual and minor glands are continuously producing
Which gland only produces secretions when stimulated?
The parotid
What is the balance between mucous and serous secretions?
Unstimulates is mixed
stimulated is mainly serous
What is whole saliva?
Saivary gland secretions, blood, oral tissue, microorganisms and food reminants
What are Exosomes?
Cell specific lipid microvesicles, can migrate through the vasculature. reside in a number of biofluids eg urin blood breast milk and saliva and we don’t yet know their function but could be to do with immune response and contain DNA
What could the saliva be used for?
Diagnostic or prognostic tests
What are the structure of the salivary glands?
They have two distinct epithelial layers. Acinar cells which surround ducts which form a large duct enterig the mouth. There are many channels and transporters in the apical and basolateral mebranes enabling transport of fluid and electrolytes.
What are the two types of acinus?
Serous and mucous.
Describe the two types of acinar cells histologically
serous are dark staining nucleus in basal third and small central ducts secrete water and alpha amylase. mucous are pale staining nucleus at the base large central duct and secrete water and glycoproteins.
What are the types of ducts in the glands?
Intralobular ducts and main excretory
What are the two divisions of intralobular ducts?
Intercalated short and narrow segments with cuboidal cells that connect acini to striated ducts. And striated ducts are major site for sodium chloride reabsorption
What is the appearace of striated ducts histologically?
Look striated basal membrane has many microbilli for transport many mitochondria for transport
Other than conduction what are the fuctnios of the ducts?
Primary saliver has lots of NaCL and is isotonic but it becomes hypotonic and NaCl also have secretions of potassium and HCO3
Which glands are the major salivary glands?
Parotid submandibular and sublingual.
Where are the parotid glands?
just in fron of the ear it has a capusule
What structures pass through the parotid gland?
The external carotid and termial branches, retromandibular vein, facial nerve.
Where is the outlet of the duct for the parotid?
above top of the molar on top
Where is the submandibular gland?
under the manduble bone there are two lobes.
What is wharton’s duct?
it secretes the saliva from the submandibular and sublingual glands into the mouth. It is positioned in the sublingual papillae
Where are the sublingual gland?
Between mylohyoid muscle and oral mucosa
What does sublingual gland secrete??
mixed but mainly mucous
What are some of the minor glands?
around Buccal labial palatal and lingual regions. at base of tounge von ebner glands that secrete serous. all other minor are mucous producers
Which nerve innervates parotid?
the 9th cranial nerve does parasympathetic
What is Xerostomia?
Dry mouth
What are the main causes form dry mouth?
Radio treatment of cancer, CF sjogrens syndrome and often medications
What are other problems with glands?
Obstructed glands with stones, infections with them from mumps and parotid has the capsules which causes pain
Degenerative from radiotherapy.
What is Sjogren’s syndrome?
Manly post-menopausal females, affects eyes, could be linked to arthritis
What is the effects of salivary gland dysfunction?
Low lubrication poor hygiene accumulation of plaque and caries gingivitis and periodontal disease and opportunistic infections
What is the effects of salivary gland dysfunction?
Low lubrication poor hygiene accumulation of plaque and caries gingivitis and periodontal disease and opportunistic infections
What is the function of bile?
Lipid emulsification and absorption, Cholesterol homeostasis, excretion of lipid soluble xenobiotics drug metabolites and heavy metals
What is bile?
A complex lipid-rich micellar solution containing water inorganic electrolytes, organic solutes, bile acids, phospholipids, cholesterol, bile pigments)
How much bile is produced a day?
500-600ml
How much of bile acids are lost each time?
5%
What makes up most of bile?
Bile acids then phospholipids cholestrol and protein small bilirubin
What are the types of bile acid?
Primary, Cholic and Chenodeoxycholic and Secondary such as deoxycholic and lithocholic acids
What produces secondary bile acids?
Bacterial conversion
What produces bile acids?
Cholesterol is used to produce it
What is the purpose of bile acid prodction?
the primary bile acids are water soluble unlike cholesterol
What happens the bile acids before the are secreted?
They are conjugated to make them less reabsorbed through the coduction to the small intestine
What is amphipathic?
Like water and fat to reduce surface tension and aid emulsification
what is the function of emulsofication?
gives a large SA for lipolysis enzymes
What is colipase?
an enzyme that facilitates binding of lipase to the droplet
How do the fatty acids and monoglycerides get into the enterocyte?
They form micells with bile acids
What happens in an enterocyte to the fats?
Packaged into the lipoproteins for transport.
What are the functions of bile acids?
Induce bile flow through osmotic effect. they are involved in digestion of dietary fats, facilitates protein absorption by accelerating hydrolysis, involved in cholesterol homeostasis, it is antimicrobial can induce genes and prevents calcium gallstones and renal stones
describe the movement of cholesterol from the liver
It passes into the duodenum and 50% of all cholesterol including dietary is reabsorbed
What do statins do?
THey inhibit HMG CoA reductase to prevent cholesterol being formed
What does Exetimibe do?
Block protein mediated transport of cholesterol across the membrane of the small intestine
What is the enterohepatic circulation like in the fasted state?
Bile acids go down the billary tract to gall bladder and get concentrated to 10x
What is the enterohepatic circulation like in the FED state?
CCK is released from duodenal mucosa which causes the sphincter of oddi to open and contract the gall bladder
What happens to bile acids in the small intestine
They stay intraluminal, they are reabsorbed in the terminal illium via the apical sodium bile acid transporter. and re enter the liver via portal circulation
How often does the circulation happen per meal?
2-3 times
What is the feedback mechanism for bile acid?
bile acids inhibit cholesterol 7 aloha hydroxylase
What is farnacoid X receptor?
Bile acids are ligands for it. this causes synthesis of Endocrine polypeptide hormen FGF19 to inhibit CYP71
what can go wrong in the circulation?
Inherited defects, deconjugation of bile acids from small bowel bacterial overgrowth, cholecystectomy can cause diarrhoea as it is just stored in duodenum.
Ileal resection where absorbed bile acids ebter colon where they inhibit water absorption/ induce secretion resulting in bile salt diarrhoea
What happens in biliary obstruction?
A stone blocks it, pancreatic carcinoma can cause malabsorption of fat soluble vitamins and fat resulting in steatorrhoea
What happens in biliary obstruction?
A stone blocks it, pancreatic carcinoma can cause malabsorption of fat soluble vitamins and fat resulting in steatorrhoea
What is the function of the colon?
Production of vitamins, absorption of water and electrolytes and excretion.
What makes faeces brown?
Urobilinogen
What are the layers of the colonic wall?
Mucosa submucosa, muscularis mucosae and muscularis propria and serosae which encapsulatied
What is the muscular layer like?
continuous circular muscle, 3 stripes of longditudinal muscle taeniae coli
What are haustrations?
bumps in and out of the surface
What is the epithelium in the bowel?
Columnar epithelium with goblet cells crypts of leibercoum
What is absorbed?
Water by osmosis, sodium is actively transported out of it
How are vitamins produced in the colon?
By bacteria produce them
What is the intrinsic nerve supply in the colon?
Meissners and Auerbach’s plexus this contraction continues on its own and is stimulated by faecal matter in the tube.
What is the extrinsic innervation?
Parasympatetic is from the vagus and the sympathetic is from the sympathetic flow
sacral parasympathetic outflow S234 keeps the poo off the floor
What is the gastro-colic reflex?
The stomach stretching and food in the jejunum leading to mass movement of the colon.
What is the structure of the anal sphincter?
There are many muscles such as levator ani internal and external anal sphincter. The internal is smooth muscle. the external anal sphincter is skeletal muscle, there are two layers of hemorrhoid veins
What happens when the rectum is empty?
both sphincters are contracted puborectalis (a sling that keeps the angle of the rectum acute) muscle is contracted
What happens when the rectum fills?
the external sphincter is relaxed, puborectalis relaxes, rectum contracts and do a valsalva maneuver (increases abdominal pressure by closing glottis and squeezing muscles
How do we know when we need to daefacate?
Pressure sensors in the rectum relax the anal sphincter, it is a sampling reflex
What could lead to constipation defaecation?
Consistency of stool, Bowel motility, physical blockage to the bowel, pelvic floor disorders
How can constipation be cured?
Drink more water, more dietary fibre, exercise, way sit on the toilet
Medical- Laxative,
What can cause diarrhoea?
Consistency of stool or frequency of movements, diseased bowel mucosa, reduced rectal capacity, pelvic floor disorder
What diseases are associated with metabilic problems?
Diabetes, obesity, high cholesterol, aorexia.
What can happen to proteins in the body?
The enter the nitrogen pool and can become tissue protein, enter the urea cycle then citric acid cycle or excreted, or can be put into pyruvate and into the TCA cycle
What can happen to carbohydrates?
glycolysis to Pyruvate or acetyl CoA and then TCA cycle.
What happens to lipds in the body?
They undergo beta oxidation to enter TCA cycle
What comes from carbohydrates?
Glucose
What are proteins brokendown into?
Amino acids
What does fat become?
triglycerides
Where is glucose absorbed?
The intestines
Where glucose used?
Muscles, Brain, RBC and adipocytes to be stored
What happens to glucose in the liver?
Insulin promotes the uptake of glucose into cells, here it can be stored as glycogen. or it can be Acetyl CoA for energy production. With excess can be converted into triglycerides can be exported by LDL
What happens to glucose in the muscle?
Stored as glycogen, or used for respiration
How is glucose used in the brain?
It is used directly for energy
How is glucose used in RBCs?
Glucose is converted into pyruvate in glycolysis and then to lactate as cant do aerobic respiration
What happens in adipicytes to glucose?
Stored as triglycerides in the cells mediated by glucose
What happens to amino acids in the bloodstream?
They enter cells and are used to construct proteins, they can makehormones or they can feed into the krebs cycle
What happens to triglycerides in the body?
can be joined to proteins to be transported to the other parts of the body chylomicrons travel in the lymphatics
What happens in the fed state?
Fuels are oxidesed to energy. excess is stored as triglycerides in adipose tissue, glycogen in the liver and muscle
What happens in the body during fasting short term?
Energy stores are broken down to produce glucose. glycogen is broken down from the liver glucagon promotes this. the glucose goes to the brain and muscles and RBCs. this is called glycogenolysis
What happens in a longer fast initially?
All glycogen is used up in stores, amino acids are used preferentially by muscle protein. lactate from RBCs and glycerol can be released from adipocytes. this is all sent to the liver where these molecules produce glucose. Gluconeogenesis
What happens in a longer fast to the fats?
Triglycerides are split into glycerol that goes to the liver for conversion to glucose, Fatty acids can be used by the kidney and muscle as a source of energy. the fatty acids can produce ketones in an emergency. this is lipolysis and is driven by glucagon
What happens in prolonged fasting?
cant break down all of the muscles as can’t move. so after a while it preserves muscles. this is when fatty acids are used and ketogenesis often takes place.
Which substances can be measured in the blood?
Glucose, ketones, insulin, lactate and triglycerides
Which hormones that regulate fuel metabolism?
Insulin and glucagon, cortisol, Adrenaline and noradrenaline, thyroxine, growth hormone and somatostatin
What does insulin do?
It is anabolic it promotes glycogen storage, fat storage and protein synthesie?
What does glucagon do?
It is catabolic it promotes glycogenolysis, gluconeogenesis and ketogenesis
What is the effect of cortisol?
Lipolysis, protein breakdown, gluconeogenesis and glycogen storage it is a preparation for a stress response
What are the effects of adrenaline?
Glycogenolysis, gluconeogenesis and lipolysis it is fight or flight hormone
What does thyroxine do?
It controls glycolysis, cholesterol synthesis, glucose uptake, protein synthesis and sensitises cells to adrenaline
What does growth hormone do?
Gluconeogenesis glycoge syntheis lipolysis, protein synthesis, decreased glucose use
What is Diet induced thermogensis?
The heat energy produced from the breakdown of food into its constituent nutrients
How is appetite controlled?
Ghrelin increases appetite and Leptin decreases hunger. high lipids gives high leptin but in obesity the body becomes desensitised
What are the foregut derivatives?
oesophagus stomach first half of duodenum pancreas liver, biliary system and dorsal and ventral mesentery ommentum
What is the dorsal mesentery?
the greater omentum
what is the ventral mesentry?
the lesser omentum
Which artery supplies the foregut?
The coealiac axis
What is the falciform ligamaent?
The free edge of the lesser ommentum that contains the ligamentum teres
Which mesentery does the liver grow in?
the lesser omentum/ventral
What are the outgrowths of the duodenum?
Two into the ventral mesentery( one pancreas the other liver) and one into the dorsal mesentery
describe the liver out pouching?
The bile ducts grow then some separate to form the liver in the ventral mesntery.it develops to the right of the midline and has overlapping mesentery and there is a bare area.
What is the portal triad like?
Has peritoneum surrounding it all they are at the edge of the lesser omentum
What is the rotation of the pancreas?
The dorsal rotates90 degrees to the left side. the ventral rotates to the same position bringing the bile ductwith it to the other pancrease.
What is the uncinate process?
the ventral pancreas is much smaller
Whar happen to the superior mesenteric artery and vein?
They get sandwiched between the two pancreases
Where is the head of the pancreas?
right by the duodenum
Where is the neck of the pancrease?
the bit that overlies the blood vessels
Where does the spleen develop?
The dorsal mesentry
Describe the rotation of the stomach
I rotates anticlockwise so the right surface becomes ventral
where is the lesser sac?
The lesser omentum and greater omentum, posteria of it is the pancreas
When does the omentum grow the most?
In puberty
When does the omentum grow the most?
In puberty
What happens in iron metabolism?
comes in to duodenum put into transferrin and can be made into blood cells muscles or in the liver. it is stored in the liver cells and reticuloendothelal macrophages
What is ferritin?
Large spherical protein with 24 units, it can contain 50000 atoms of iron an is in the cytoplasm and in the serum, the amout in the serum tells us how much iron in the body.
What is ferritin excess?
excess iron storage disorder, hereditary haemochromatosis, haemolytic anaemia, multiple blood transfusions, iron suppliments. can be non-iron overload like liver disease
What acuses ferriting deficeincy?
Not enough iron
What are vitamins used for?
Gene activators, free-radical scavengers, coenzymes or cofactors in metabolic reactions
Which vitamins are fat soluble?
ADEK
Which vitamins are water soluble?
B and C
How long do water soluble vitamin stores last?
Not long as easily washed out of body
What is vitamin A used for?
Used for help in eye function, comes from carrots and meat. it forms rhodopsin in rods of the eye and for spermatogenesis for growth and membranes.
What is a defficiency in vitamin A?
Rare in affluent countries can lead to blindness night blindness can happen in fat malabsorption.
What happens with excess vitamin A?
Not very very bad but can lead to nausea vomiting headaches, can get yellowing of the skin
What is vitamin D used for?
increased intestinal absorption of calcium, resorption and formation of bone, reduced renal excretion of calcium.
What is the problem with vitamin D deficiency?
Rickets in children osteomalacia in adults
What is the role of sunlight in vitamin D?
sunlight converts it from 7dehydrocholesterol, into cholecalciferol, can come from others and its stored as 25 hydroxyvitamin D then converted to 1,25 dihydroxy to be used
What is vitamin E used for?
In antioxidants
How is vitamin E stored?
In adipose as fixed pool, and in licer and plasma as a labile store
What is defficiency and excess of vitamin E like?
Caused by fat malabsorption CF, premature infants, get haemolytic anaemia, myopathy, retinopathy ataxia and neuropathy in excess its not too harmful
What is vitamin K used for?
It is stored in licer but then given to LDL. it is used for clotting factors 2,7,9,10 it activates some.
What does a defficincy in vitamin K
Haemorragic disease of the nowborn not usually a problem in adults.
What happens in excess vitamin K?
K1 is safe, synthetic forms are more toxic, oxidative damage and red cell fragility
What is the use of vitamin C?
Collagen synthesis, antioxidant and iron absorption
What happens in vitamin C deficiency?
Scurvy easy bruising and bleeding teath and gum disease hair loss, quick treatment
What happens in excess?
Can cause GI side effects
What is vitamin B12 deffiecinecy?
caused by Pernicious anaemia, autoimmune destruction of IF producing cells in stomach.
malabsorption by lack of acid pancreatic disease or veganism
causes macrocytic anaemia and peripheral neuropathy in prolongued deficiency
What are the forms of B12?
methylcobalamin and 5-deoxyadenosylcobalamin
How is B12 absorbed?
Binds to R protein to protect from acid, then binds to intrinsic factor to be absorbed in the terminal ilium
What is folate?
Found in lots of fortified foods involved in coenzymes for DNA synthesis
What is the folate deficiency like?
malabsorption taking drugs can cause it, symptoms are high homocystine levels macrocytic anaemia and foetal abnormalites
What are the two clotting pathways?
intrinsic which is activated by contact, the extrinsic pathway activated by CF7 touching tissue factor.
What do the clotting pathways lead to?
Common pathway of thrombin turning fibrinogin into fibrin clot
What is prothrombin time?
The clotting time via extrinsic pathway
What is the activated partial thromoplastin time?
measures intrinsic pathway measurement
What does prolongues PT mean?
Prolongued PT may be deficiency in the synthetic capacity of the liver
What are the two phase of biotransformations of waste products?
Add or expose functional groups to the molecules such as OH SH NH2 or COOH to try and increase hydrophilicity slightly
Phase 2 i biosynthetic where the molecules are conjugated with endogenous molecules like glucoronic acids. it forms covalent bnds and increases hydrophilicity
What is glucuronidies?
Hydrophilic there are a ring with lots of OH
what is the purpose of the drugs being detoxified
to make it more hydrophilic so it can be excreted
What is Cytochrome P450?
There are 10 moan groups encoded by about 60 genes they all are present in sER hence microsomal enzymes, the oxidise substrates and reduce water. they use NADPH they are indicible and can be modified by drigs and generate fre radicals
Why is Cytochrom P450 important?
It is involved in lots of drug drug reactions one durg can eaffect metabolism of another. they can also be inhibited by food. this can cause overdose
What can affect clozapine?
Barbituates rafamoicin and smoking can induce it and ciproflaxin are known to inhibit the cytochrome enzyme.
What are the clinical uses of this proses of biotransformation?
Some drugs are converted into inactive forms quickly, others are changed to another chemical with the same effect, some got from inactive drugs to active drugs, others could cause toxic products during breakdown
How are opiates being metabolised?
Codine molecule is morphone with OH replaced by methyl, so better distributed around the drug, this is then changed to morphine a useful product also
What happens to paracetamol?
Paracetamol is glucuronidated or sulohonated to make it more easily excreted but alternatively, some is excreted as NAPQI which can build up in overdose
What are some phase two reactions?
Glucoronidation sulphation, Glutatione, Methylation, Acylation, Phosphate conjucation
What is special about ethanol?
It doesnt fit phase one or phase 2, it is reduced to acetaldehyde, which can be harmful. this can be done from microsomal systems as well this is worse in frequent drinkers. it is concerted to acetate in the liver but with the liver is overwhelmed it causes a bulid up of acetaldehyde thsi buildup causes damage
What are the parts of an amino acid?
Amino group NH2 acid group COOH and a sidechain
What is the difference between dipeptides, polypeptides, proteins?
Dipeptide is two AA polypeptide is less than 50AA protein is more than 50AA
How is nitrogen excreted in the kidney?
Not as protein but as urea
When might you have a negatice nitrogen balance?
Protein malnutrition, severe illness or sepsis, corticosteroids, cancer or deficiency
What is Kwashiorkor?
Protein-energy malnutrition
What happens to amino acid in the fed state?
Dietary protein is absorbed as amino acids in the gut. it is take to the liver where it can be conerted into proteins which travel to cells or go as lipoproteins or amino acids in the blood stream.can be converted to glucose
How is amino acid absorbed?
co transport with sodium and amino acids
What are essential amino acids?
Ones that the body cannot synthesis on its own
What are conditionally essential amino acids?
alanine is used to produce tyrosine. so can be produced but only in the presence of others
Non essential amino acids?
They are substances that are very easily produced by the body
What are glucogenic amino acids?
Carbon backbone can be used to produce glucose
What is a ketogenic amino acid?
is one that the backbone can be used for acetyl CoA
What are the two ketogenic amino acids?
Leucine and lysine
What is the way amino acids can be joined with the respitation?
They can enter at many stages, becoming pyruvate or CoA
What is transamination?
conversion of an amino acid and an alpa ketoacid into a different alphaketo acid and producing another amino acid. swappin the amino goup
What is the clinical use of transamination?
It is a good identifier of liver function
What is transamination of alanine?
Alanine+ alphaketoglutarate—> pyruvate+ glutamate
What is the use of transamination of alanine?
it is a shuttle for ammonia to the liver where it can be processed
How is ammonia excreted?
it is bound with bicarbonate to carbamyl phosphate which enters the urea cycle.
What happens to amino acids in the fasting state?
protein is broken into AA in the muscle and then put into TCA cycle and sent out to the other organs to be used.
Where can the urea cycle happen?
In
Where can the urea cycle happen?
In the liver only
Why do some proteins have bigger lifetimes?
Degredation factors: faulty ageing or obsolete, signal transduction, flexible system to meet protein/ energy requirements of environment.
What are the two main means of protein breakdown?
Proteasomes(ubiquitin) and lysosomes
What is ubiquitin?
A small protein that marks proteins for destructions it uses lysine residues. there are three enzymes that are used.
What is a proteasome?
Reacts to ubiquiting and contains proteolytic enzymes
What is the N-terminal rules?
The group at the end of the protein chane determins if it is destroyed. eg PEST or cyclin destruction box
What is the alanine glucose cycle?
Glucose can be sent to the cells and there it turns into pyruvate that can accept amine group from then the alanine can go to the liver and be turned back into glucose alphaketo-glutamate is made from glutamate
What is the aim of the urea cycle?
To turn ammonia to urea
What is the ornithine cycle?
Ammonia is added to citrulline to produce arginine and urea then ornithing has ammonia and CO2 to make citrulline
What can the urea cycle be linked to ?
the aspartate argininocuccinate shunt of the citric acid cycle
Where does the urea cycle take place?
Ornithine and citruline parts in the mitochondrion. the rest in the cytoplasm.
How can you test for inherited metabolic disease?
test for bulidup of things in the cycle.
What happens to carbamoyl phosphate when it is not removed?
It prodcues oratate that can be picked up in urine of patiens with ornithine transcarbamalase problems
What is a good test for liver problems?
Ammonia testing
What is the role of the epithelial cells in the GI tract?
To absorb water and ions and secrete them
How long is the small intestine?
6m aprox
What increases the surface area of the small bowel?
The vili and the crypts
What is the function of the crypts?
they secret substances mainly
how is the trans cellular process facilitated?
The sodium potassium pump pumps sodium into the blood and potassium into the cell. Sodium moves from the intestinal lumen into the cell bringing other substances with it
What facilitates secretion in the intestine?
Chloride secretion coming into the cell it infuences cAMP which influences the chloride into the lumen and secretion of water.
What are the symptoms of digestive systems?
Diarrhoea, weight loss and failure to thrive
What happens in coelia disease?
the villi become dammaged?
What is prevalence in UK?
1 in 100
What is gluten?
protein is in wheat barley and rye
Why are rehydration drinks very salty?
The salts are absorbed and draw water into the body
Where is carbohydrates broken down first?
In the mouth
What breaks starch into sugar?
amylase to maltose then maltase to glucose
What is sucrose made of?
Glucose and fructose
What is lactose made of?
Glucose and galactose
How is glucose absorbed?
secondary active transport
How is fructose absorbed?
Facilitated diffusion
What molecules are broken down in the mouth?
carbohydrates and fats
How are amino acids absorbed?
They are absorbed by facilitated diffusion.
How do fats get absorbed?
As free fatty acids through the membrane
What enzumes are present in the stomach?
Pepsin and Lipase
What enzymes are released by the pancreas?
Amylase, lipase and colipate, phospholipase, trypsin and chymotrypsin
What enzymes are in the small intestine?
Disaccaridases enterokinase(activates trypsin) peptidases
What do chief cells do?
gastric lipases and pepsinogen
What are the pancreatic fuctions?
Endocrine (insulin glucagon)
Exocrine- bicarbonate and enzymes
What is a pancreatic islet?
Alpha cells and beta cells and the acini what secrete enzymes into the pancreatic duct.
What happens at the parts of the duct?
End produces enzumes, closer does HCO3- secretion, HCO3-.Cl- exchange for pH
Where is CF involved in the pancreas?
It is responsible for chloride and bicarbonate secretion protein
What chemicals stimulate the pancreas?
Secretin and cholecystokinin
Where is CCK produced?
In the duodenum and jejunum by the I cells
Why is bicarbonate secreted?
It buffers the acid from the stomach.
What helps activation/production of trypsin?
Trypsin and enterokinase
What activates chymotripsin?
Trypsin
How can you divide diseases of the panceas?
Intrinsic problems CF Cancer Autoimmune, Not linked directly could be under stimulation of pancreas, post surgical gastric resection whipple’s
How do you image it?
MRI and CT as ultrasound doesn’t work well externally? Ultrasound through the stomach
How can pancreatic insufficiency be treated?
Enzyme replacement, bone health assessment stop smoking treat underlying cause
