Gastro Flashcards
The gastric mucsoa is divided into?
1) Columnar epithelium - protective mucus layer
2) Gastric glands - intersperse the mucosa and contain secretory cells
Which cells are included in the gastric secretory cells?
1) Mucus cells - secrete mucus and are situated at the opening of the gastric gland
2) PEPtic/chief cells - found at the basolateral aspect of the gastric glands and secrete PEPsinogen
3) Parietal cells - secrete HCL and IF
4) Neuroendocrine cells - eg) Gastrin
What is the function of the stomach acid?
1) Tissue breakdown
2) Converts Pepsinogen to active Pepsin
3) Forms soluble salts with calcium and iron - aids absorption
4) Acts as an immune defence - killing micro-organisms
How is gastric acid secreted?
Secreted by PARIETAL cells - when activated, deep clefts form in the APICAL membrane
These canaliculi allow acid to be secreted into the stomach
Cl- and H+ pumped from parietal cells (ACTIVE)
by 1) H+/K+/ATPase 2) Cl- pumped by chloride channel and Cl- and K+ co transport system (note k+ cycling)
What is Alkaline tide?
1) Hydroxyl ions from H+ formation are catalysed by carbonic anhydrase produces HCO3-
2) HCO3- is then exchanged for Cl- on the basolateral surface of the cell
3) Secretion of HCO3- acts as a protective mechanism for the mucosa
How does Pepsinogen seretion work?
Peptic cells produce pepsinogen, a proteolytic enzyme that hydrolyses peptide bonds
Pepsinogen is secreted into gastric glands (inactive form).
Acidic environment in stomach activates pepsin (active)
Where is mucus secreted?
Neck of the gastric glands
Forms a protective later, alkaline pH to neutralise the acid
Other than mucus layer, what other ways is stomach lining protected from digestion?
1) Tight epithelial junctions
2) Prostaglandin E secretion has a protective role by increasing the thickness of the mucuss layer, stimulating HCO3- prodcution and increasing blood flow in the mucosa - promoting healing in damaged areas.
What is the the function of Intrinsic factor?
Secreted from parietal cells.
Binds VitB12, then absorbed in complex with the IF via specialised receptors in the ileum.
What are the three phases of Gastric secretion?
1) Cephalic - sensory (sight,smell) thought of food
Impulses from appetite centre in the hypothalamus to the stomach - 30% of gastric secretions
- G cells release gastrin (gastrin also stimulated H2 release)
- Direct impulse (ACh) to strimulate gastric glands
- Release Histamine from mast cells - stimulating parietal cells via H2 receptors
2) Gastric - 60% of secretion
Distension of the stomach and chemical composition lead to release from the vagus.
3) Intestinal - 5%
Stimulated by food in the duodenum, leads to release of gastrin from G cells in duodenal mucosa
What other factors infulence gastric secretion?
1) Secretion of Gastrin is inhibited when the pH falls to around 2-3
2) Somatostatin secreted from D cells inhit gastrin secretion
3) Secretin produced in Duodenal mucosa is released in response to acid in the duodenum
4) Fatty food in duodenum leads to CCK and GIP- inihits gastrin
What factors influence gastric emptying?
1) Gastric volume: increase volume = increase rate of emptying
2) Fatty foods -> CCK and GIP released by SI increase contractility of the pyloric sphicter
3) Proteins: Stimulate Gastrin release - increased contractility of pyloric sphincter
4) Acid: in duodenum –> Secretin release
Secretin inhibits antral contractions and increases contractractility of PS. Also stimulates HCo3- from pancrease
5) Hypertonic chyme delays gastric emptying
How is the vomiting reflex co-ordinated?
Co-ordinated by vomiting centre in Medulla
Stimulation leads to motor impulses passing along cranial nerves 5,7,9,12, intercostals, abdominal muscles and diaphragm
Three choices for medical treatment of peptic ulcer disease?
1) Reduce acid secretion
2) Mucosal protection
3) Antacids
Three groups of drugs for reducing acid secretion?
1) Histamine (H2-receptor) Antagonists
- eg) Ranitidine. Acts by blocking H2 receptors on parietal cells (inhibiting cAMP)
2) Muscarinic antagonists - eg) Pirenzepine no longer used. M1 receptor antagonist for parietal cells
3) PPIs eg) Omeprazole - Acts directly on H+ K+ ATPase - irreversably binds to sulphydryl groups on the proton pump
What are the indications of a surgical management of peptic ulcer disease?
1) Chronic unhealed ulcer
2) Failure to heal after more than two courses of medical treatment
3) ?Malignancy
4) Complications - eg) perf/bleeding
What are Post- gastrectomy syndromes?
1) Malnutrition due to reduced stomach volume
2) Deficiency - Vitamin B12 def (no IF). Incorrect Iron ionic state
3) Early Dumping sydrome - Rapid gastric emptying of a hyperosmolar meal into the small bowel - third space loss, dizziness, weakness and palpitations
4) Late Dumping syndrome - rapid swings in insulin secretion in response to the glucose load in the small bowel - rebound hypoglycaemia
5) Diarrhoea
6) Bilious vomiting - loss of pylorus
7) Infection - TB - no HCL
8) Gastric remanent Malignancy due to increased duodenal refulx
What are the effects of vagotomy?
1) Reduced gastric acid secretion
2) Delayed gastric emptying
3) Failure of the pylorus to relax prior to gastric peristaltic wave
4) Reduced pancreatic exocrine secretions
5) Diarrhoea secondary to loss of vagal control of the small bowel
6) Increased Large bowel Ca risk due to excessive bile salts reaching the colon
What are the different cell types in the crypts of Lieberkhun (small intestine)?
1) Undifferentiated cells to replace enterocytes
2) D-cells: produce somatostatin
3) S- cells: produce secretin
4) N- cells: produce neurotensin
5) Enterochromaffin cells: 5-hydroxytyptamine
What are the physiological effects of duodenal resection?
Duodenectomy leads to
1) Ulceration of small bowel
2) Malabsorption, impaired fat emulsification
3) Dumping: loss of control over gastric emptying leads to uncontrolled passage of chyme in to the small bowel
What are the physiological effects of terminal ileal resection?
Removal of terminal iluem leads to
1) terminal ileum is the site of bile salt reabroption, loss of this site increases bile salt in colon and increases risk of colonic malignancy.
Due to loss of enterohepatic circulaation, therre is a decrease in bile salt pool, increase risk of cholesterol gallstones
2) Vit B12 deficiency - macrocytic anaemia, degeneration of the spinal cord if not corrected
3) Diarrhoea
How is the pancreatic fluid component maintained?
Epithelial cells that line the ducts form the fluid component of pancreatic juice
1) HCO3- is transported into the lumen in exchange for Cl- and directly via a luminal channel
2) Na+ and K+ are exchanged for H+ (reaction catalysed by carbonic anhydrase)
3) Na+ follows HCO3- to maintain electrochemical neutrality
4) H2O follows osmotic gradient created by the movement of Na+ HCO3-
How are inactive proteolytic enzymes activated?
Key component is activation of trypsinogen to trypsin by enterokinase (duodenum) and alkaline environment
What are the three phases of pancreatic exocrine secretions?
1) Cephalic - Vagal stimulation Ach and VIP and also stimulus from gastrin. Vasodilation, activate acinal and ductal cells
2) Gastric - distension and gastrin - vagal gastropancreatic reflex
3) Intestinal - 60-70% stimulus
- CCK (cholecystokinin) (mainly fatty foods and AAs) release of a fluid rich in exnzymes from acinar cells
- Secretin (Acid) release of bicarbonate-rich fluid
What are the physiological effects of pancreatic resection?
1) Malnutrition: Inadequate digestion of protein and lipids due to loss of proteolytic and lipolytic enzymes. Progressive deficiencies in fat soluble (VIT A,D,E,K)
2) Malabsorption: loss of alkaline pancreatic secretions leads to failure to neutralise gastric chyme and leads to Fe2+, Ca2+ and PO4- malabsorption
3) Diabetes Mellitus - absolute insuline deficieny
Summarise bilirubin metabolism
1) RBCs are broken down in the spleen and release unconjugated bilirubin
2) Unconjugated bilirubin has to be bound to albumin
and transported to the liver
3) Bilirubin is conjugated to glucuronide - water soluble
4) Bilirubin is stored in GB and excreted in Bile
5) Once Bilirubin enters bowel, intestinal bacteria convert to urobilinogen
6) Some excreted in the faeces (stercobilinogen), some excreted in urine
What is prehepatic jaundice and what are the lab findings?
Excessive RBC haemolysis, causing unconjugated bilirubinaemia - Anaemia - Increased LDH - Decreased haptoglobin - Increased urobilinogen in urine Common causes - Hereditary spherocytosis - Sickle cell - G6PD Deficiency - Transfusion reactions - Drugs - Burns
What is Hepatocellular jaundice and what are the lab findings?
Element of cholestasis as hepatocytes swell and obstruct the flow of bile Combination of conjugated and unconjugated - AST+ALT increased - ALP increased Abnormal clotting tests Causes - Viral (Hep a,b,c,e, EBV) - Autoimmune - Cirrhosis - Liver tumours and Metastasis
What is cholestatic jaundice and what are the lab findings?
Intrahepatic cholestasis is similar to helpatocellular jaundice Causes: Hepatitis, drugs, PBC Extrahepatic cholestasis occurs due to obstruction of the large bile ducts distal to the canaliculi - Gallstones - Bilary stricture - Carcinoma - Pancreatitis - Sclerosing cholangitis Lab tests - Bilirubin in the urine - Characteristc dark colour - Increased ALP and Gamma GT - Increased Liver ALT and AST
What are the physiological effects of cholecystectomy?
1) Loss of concentrating action of the gall bladder can lead to increased flow of bile, leading to reflux and bilary gastritis
2) Fat intolerance and malabsoprtion, can produce abdominal pain and diarrhoea
