Pancreas, small intestine, iron metabolism and hepatitis Flashcards
What are the 2 forms of cellular iron storage
Ferriting and Haemosiderin
What are the properties of ferritin?
Soluble, stores iron, but readily available from reticuloendothelial system, small amounts in serum used to test overall iron stores
What is haemosiderin?
Insoluble conglomerates of ferritin, iron is only slowly available
In what condition does serum ferritin decrease?
Iron deficiency anemia
When does serum ferritin increases?
In iron overload, and in tissue inflammation as it is acute phase protein
What protein transfers iron in plasma?
Transferrin (Tf)
What type of protein is transferrin?
Glycoprotein with 2 iron binding domains, shaped as Y
Where is transferrin synthesized?
In hepatocytes
What is the normal saturation of transferrin with Fe and how is its concentration controlled?
30% saturated with Fe3+, if iron decreases levels of Tf increase and vice versa
What is the body content of iron?
4 mg
What is the daily iron need and what is the intake on Western diet?
Daily iron need is 1 - 2 mg/d and in Western diet the intake is 15 - 20 mg/d
How much iron is lost per day during menstruation?
1 - 2 mg/d
How does the iron end up stored in RES?
Iron is absorbed and bound to Tf, then used in Myoglobin enzymes and absorbed into RBCs from which it is stored in the RES
How are the bodily levels of iron controlled?
By absorption as there is no excretory mechanism
What types of iron exist and in which foods it can be found?
Haem iron - red meat; Non-haem iron - white meat, green vegetables, cereals
Where is iron absorbed in the GI?
Predominantly in duodenum
What cells absorb iron?
Duodenal enterocytes
How is Haem transported absorbed into the enterocyte?
Diffuses into the cell and is broken down by Haem oxygenase into Fe2+, biliverdin and CO2 and moves into the labile iron pool in the cell
How is non-haem iron absorbed into the enterocyte?
Released from food and must be reduced from the ferric acid to ferrous (Fe2+) by duodenal cytochrome b1 (dCytb1), influenced by Vit C; Fe2+ is than transported by divalent metal transporter 1 (DMT1) and then taken into the labile iron pool
What happens to Fe2+ inside the duodenal enterocyte?
Either binds to Ferritin, moves to mitochondria or is transported out by Ferroportin and Hepcidin
What is Ferroportin?
A transmembrane protein releasing Fe2+ out of the cell during absorption but also from its store in macrophages
What is Hepcidin?
Protein which inhibits iron transport by binding to ferroportin, resulting in breakdown of the transporter - the interaction is the most important regulator of GI iron absorption
What happens to Fe2+ as it is released from the enterocyte?
Oxidized into Fe3+ and binds to Transferrin
How is iron stored in RES?
RES macrophages get iron from effete RBCs, store iron as ferritin or haemosiderin and release it by controlled Ferroportin and Hepcidin
How much iron does RES store?
500 mg of iron
How is Tf-iron taken up into cells and into which ones?
Taken up via Tf receptors on erythroblasts, hepatocytes and others
Where is transferrin synthesised?
In the liver
What is the total amount of iron transported per day?
Up to 50 mg of iron can be transported, although only 4 mg can be bound to Tf at any one time
What produces Haem in the erythroblast?
Mitochondria, first step in the pathway is mediated by ALA-S2
What are the properties of Haem
Able to reversibly bind O2 without undergoing oxidization or reduction
Describe iron metabolism regulation by Hepcidin
‘Low iron’ hormone - reduces levels of iron in plasma by binding ferroportin and thus reducing iron absorption and iron release by macrophages
Where is Hepcidin synthesised
In the liver
What are the results of Hepcidin loss?
Increased GI absorption, increased RES iron release, increased TF% saturation and parenchymal iron overload
What is parenchyma?
The functional tissue of an organ as distinguished from the connective and supporting tissue
What is the most likely cause of iron deficiency anaemia in males and post-menopausal women?
GI blood loss
What is the most likely cause of iron deficiency anaemia in young women?
Menstrual blood loss or pregnancy
What is celiac disease and how does it affect iron absorption?
Blunting of villi, villus atrophy, enlarged hyperplastic crypts and increased infiltration of lymphoid cells in the lamina propria and epithelium, results in abnormal absorption
What are the haematinic deficiencies in Coeliac disease in order from the most to least likely
Folate deficiency, iron deficiency, vitamin B12 deficiency
What is Sideroblastic anaemia
Erythroblasts take in iron but do not change it into haem, mitochondria become paralysed around the nucleus
What is Hereditary Haemochromatosis
An autosomal recessive disorder of iron metabolism causing iron overload
What are the causes of Hereditary Haemochromatosis
Abnormalities of the HFE gene, most commonly homozygous C282Y mutation of the HFE gene
What is the relationship between HFE mutation and HH?
Reduce hepsidin production and thus Tf can become 100% saturated while there is free serum iron
What are the laboratory findings in Hereditary haemochromatosis?
Increased Transferrin saturation, increased iron and increased Ferritin
What are the consequences of Hereditary haemochromatosis?
Fibrosis/cirrhosis of the liver, diabetes, arthritis, cardiomyopathy, skin bronzing
What is the treatment of Hereditary Haemochromatosis?
Venesection weekly, than at increased periods; monitoring ferritin and transferrin saturation
What is the estimated total body iron in somebody with HH?
20 mg or more
Define acute hepatitis
Inflammation of the liver,
What would be the clinical findings in acute hepatitis, including LFTS
Raised ALT and AST, jaundice and clotting derangement
What are the causes of acute hepatitis?
Infections: Hep A, B, C, D, E, Malaria, Syphilis
Define chronic hepatitis
Hepatitis virus present for more than 6 months, variable changes in liver function
Outline characteristics of hepatitis A
RNA virus, survives for months in contaminated water, virus is shed via billiary tree into gut, no chronic carriage and good immunity after infection
How is hepatitis A virus transmitted?
Faeco-oral transmission, contaminated water and food, person-person, humans only reservoir
How is hepatitis A diagnosed?
Test blood and stool for IgM or RNA; deranged liver function tests
What is the incubation period of hepatitis A?
30 days
What are the symptoms of hepatitis A?
Fever, abdominal pain, diarrhea, jaundice, itch, muscle pains
What is the severity of hepatitis A and what are its determinants?
Self-limiting illness, age is main determinant of severity - symptoms and mortality rate increases with age, low mortality overall
What is the treatment for hepatitis A?
No specific treatment, maintain hydration and avoid alcohol
Outline the hepatitis A vaccine
Inactivated virus, 95% efficacy, protection for 4 weeks after 1st dose, 2nd dose gives life protection
To whom is hepatitis A vaccine given?
Pre-exposure - travellers, homosexual men, chronic liver disease patients, IVDU
Post exposure - outbreak control
What is hepatitis A immune globulin?
Pooled immunoglobulin giving 3-6 months immunity, given pre-exposure if allergic to vaccine, <4 weeks till travel, or to control outbreak
Describe features of hepatitis E
RNA virus with 4 genotypes, more common than Hep A
What is the incubation period of Hep E?
40 days
How is Hep E transmitted?
Faeco-oral, pork products, minimal person to person transmission
What does Hep A virus look like?
Closely packed colony of rounded viruses
What does Hep E virus look like?
Loosely packed rounded viruses
What are the symptoms of Hep E?
Similar to Hep A plus rare reports of neurological effects
What is the fatality rate of Hep E?
1-3%, higher in pregnant women
What is the treatment for Hep E?
Supportive, no vaccine
What are the neurological manifestations of Hep E?
Guillaine Barre syndrome, encephalitis, ataxia, myopathy
Define encephalitis
Inflammation and swelling of brain
Define ataxia
A neurological sign consisting of lack of voluntary coordination of muscle movements that includes gait abnormality
Define myopathy
A disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness.
Define Guillaine Barre syndrome
A rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system
What is the type causing Hep B?
Hepadnavirus - DNA virus
What is the estimated number of people that die due to Hep B
2 million deaths per year
What are the consequences of Hep B?
Chronic liver inflammation, as the virus constantly replicates it causes liver cirrhosis and failure, upper GI haemorrhages, hepatoma - hepatic cancer
What does Hep B virus looks like?
Rod like shaped single viruses
How is Hep B transmitted?
By blood (transfusion, transplants, contaminated needles. mother to baby), by bodily fluids (sexual intercourse)
What is the incubation period of Hep B?
2-6 months
What are the symptoms of Hep B?
Fever, fatigue, jaundice, myalgia, joint pains
What role does age play in Hep B?
Determines severity of illness and risk of chronic infection
What is the common outcome if a newborn or young child compared to adult is infected with Hep B?
Usually asymptomatic, but this leads to chronic infection, adults are symptomatic but can clear the infection
What are the complications of Hep B?
Weight loss, abdo pain, fever, cachexia, bloody ascites, enlarged liver
What are the problems in chronic Hep B?
Development of chronic liver disease in 25%, cirrhosis, decompensation, Hepatocellular carcinoma, death
What is the natural course of Hep B infection?
After infection HBeAG positive and period of immune tolerance, than ALT increases and HBv DNA decreases this process is associated with liver inflammation and fibrosis - immune clearance, then low replicative state and lastly reactivation, HBeAg negative and further liver damage
How many people with chronic Hep B will be identified by sAg?
more than 6/12
What are the 2 groups that Hep B carrier are divided into?
eAg +ve (early disease) and eAG -ne (late disease)
What are characteristics of eAg +ve Hep B patients?
High viral load, high risk of chronic liver damage and HCC, highly infectious
What are characteristics of eAg -ve Hep B patients?
Low viral load, lower risk of CLD and HCC, less infectious
What is the treatment for acute Hep B?
No treatment
What is the treatment for chronic Hep B?
Treat those with liver inflammation, aim is to suppress viral replication, some with clear sAg spontaneously
What are the 2 types of therapy for chronic Hep B?
Immunological and antiviral drugs
Describe the immunological treatment of chronic Hep B
Pegylated interferon alpha - increased cellular immune response, lots of side-effects
Describe the antiviral drugs in treatment of chronic Hep B
Suppress viral replication
Tenofovir and Entecavir
How is hep B prevented?
Education, screening of pregnant women and doctors, immunisation, protect blood supply and hospital supplies
Describe basic characteristics of Hep D
ssRNA virus, requires HBV to replicate so need to either catch them at the same time or already be infected with D
How is Hep D transmitted?
Same as for Hep B - bodily fluids
How is Hep D treated?
Peg IFN
What does Hep D virus looks like?
Rounded single compartments, RNA with protein coat
Outline Hep C
ss RNA virus, multiple genotypes, no vaccine and no reliable immunity after infection
How is Hep C transmitted?
Injecting drugs, transfusion and transplant, sexual and vertical transmission is rare
What is the incubation period of Hep C?
6 - 7 weeks
How many patients with acute Hep C will be symptomatic?
25%
How many patients infected with Hep C will develop chronic infection?
70%
How many percent of patients with Hep C will develop cirrhosis or hepatocellular carcinoma?
25% cirrhosis, up to 5% HCC
How is Hep C diagnosed?
By screening of high risk groups, anti HCV IgG positive = chronic infection or cleared infection, PCR or antigen positive = current infection/viraemia
How is Hep C treated?
Pegylated interferon alpha and ribavarin; direct acting antiviral (stop replication and assembly of virus, 95% success rate)
What is sAg and what it signify?
Surface antigen - marker of infection, if positive then now infected
What is sAb and what it signify?
Surface antibody - marker of immunity, cleared but have antibody, or vaccinated
What is cAB and what does it signify?
Core antibody - either have the infection or had it in the past
What is eAg and what does it signify?
E antigen - suggests high infectivity, how far into the infection a patient is, more antigen, more infected
What is eAb and what does it signify?
E antibody - suggests low infectivity, more antibody less infected
When is HBV infection diagnosed?
If sAg or DNA are detectable
Where is pancreas located?
Posterior to stomach, extending from duodenum to spleen
What parts of pancreas are peritoneal?
The tail of pancreas, rest is retroperitoneal
Where does the head of pancreas lies?
Within the C shaped space created by duodenum
What is uncinate process and where does it lie?
Projection from the lower part of the head of pancreas, passes posterior to the superior mesenteric vessels
Where does neck of pancreas lie in relation to the superior mesenteric vessels?
Anteriorly
What are the parts of the pancreas?
Uncinate process, head, neck, body and tail
Where does the tail of pancreas lie?
Between layers of the splenorenal ligament
What is the covering of pancreas?
Thin collagenous capsule which extends as a delicate septa between lobules; contains vasculature, lymphatic vessels, nerves and excretory ducts
Describe the course of the pancreatic duct
Begins in the tail, enters the head and turns inferiorly, in the lower part of the head joins the bile duct and forms the hepatopancreatic ampulla (ampulla of Vater) which enters the duodenum at the major duodenal papilla
Where does the Accessory pancreatic duct empty?
At the Lesser duodenal papilla
What is the blood supply of pancreas?
Gastroduodenal artery, anterior and posterior superior pancreaticoduodenal artery, dorsal pancreatic artery, anterior and posterior inferior pancreaticoduodenal artery
Which arteries that supply the pancreas have common origin in Celiac trunk?
Gastroduodenal which gives rise also to ant.+post. superior pancreaticoduodenal arteries, dorsal pancreatic artery and great pancreatic artery
Which artery supplying the pancreas originates in the superior mesenteric artery?
Anterior and posterior inferior pancreaticoduodenal artery
Which vein drains the pancreas?
Splenic vein
What nerves supply the pancreas?
Vagus nerve and thoracic splanchnic nerve fibres from the superior mesenteric and celiac plexuses
Name the 2 functional components of the pancreas
Exocrine and endocrine components
Outline the structure of the exocrine component
Closely packed secretory acini that drain into a highly branched duct system
How is the stucture of exocrine component of the pancreas suported?
By interlobular ducts and their supporting tissue
What is each acinus made up of?
An irregular cluster of pyramid shaped secretory cells
Describe the coure of exocrine ducts
Begins as a central lumen surrounded by accinus, this continues as intercalated ducts which drain into intralobular ducts and then interlobular ducts in the septa of the gland
What epithelium can found in the pancreatic ducts of the exocrine component?
Simple cuboidal epithelium which becomes stratified cuboidal epithelium in the larger ducts
Is the acinar vascular system connected with the endocrine system?
No, it is independet
Describe acinar cells
Typical protein secreting cells, triangular shape with apices projected into the central lumen, have loads of rough ER and eosinophilic secretory vesicles, produce zymogen granules which are released by exocytosis
Describe centroacinar cells
Pale nuclei, terminal lining cells of intercalated ducts, secrete water, Na+ and bicarbonate ions
What maintains the secretion of bicarbonate by the centroacinar cells?
Cystic fibrosis transmembrane conductance regulator that also provides Cl-
What are the cells of the exocrine component of pancreas?
Acinar cells, Centroacinar cells, goblet cells, enteroendocrine cells, myoepithelial cells and serous cells
Describe the endocrine component of the pancreas
Composed of Islets of Langerhans and Insuloacinar portal system; mainly to regulate glucose metabolism
Describe the insuloacinar system of the endocrine component of the pancreas
Each islet is supplied by different arteriole forming a capillary network, leaving venules supply blood to the acini and thus locally control the exocrine component
How much volume has each component of the pancreas?
Endocrine - 2% and exorcine 98%
Name the beginning and end point of the small intestine
Pyloric orifice and ileocecal fold
How long is the small intestine?
3 - 7 m
How long is the duodenum?
26 cm
How long is the jejunum?
3.5 m
How long is the Ileum
1.5 m
How does the diameter changes across the small intestine?
Narrows
What is the shape of duodenum?
C-shaped
Where is duodenum located?
Above the level of umbilicus, retroperitoneal
By which ligament is the duodenum connected to the liver?
Hepatoduodenal ligament
How is the duodenum divided and what vertebral level are they on?
Superior - L1, descending - L3, inferior - L3 and ascending - L2 part; also D1 to D4
Describe the superior part of the duodenum
From pyloric orifice to the neck of the gallbladder, passes anteriorly to the bile duct, gastroduodenal artery, portal vein and inferior vena cava, common place for duodenal ulcer
Describe the descending part of duodenum
From the neck of the gallbladder to the lower border of the vertebra L3, anterior surface is crossed by the transverse colon, contains the major and minor duodenal papilla
Where is the junction of midgut and foregut?
Below the major duodenal papilla
Describe the inferior part of the duodenum
Longest, crosses the inferior vena cava, the aorta and the vertebral column, crossed anteriorly by the mesenteric vessels
Describe the ascending part of the duodenum
Goes up and terminates at the duodenojejunal flexure, passes to the left of aorta
Describe the duodenojejunal flexure
Surrounded by a fold of peritoneum containing muscle fibres called suspensory muscle ligament of duodenum
Name the arteries that supply duodenum
Branches from the gastroduodenal artery:
supraduodenal artery;
duodenal branches of ant, and post. superior pancreaticoduodenal a.,
duodenal branches of the ant. and post. inferior pancreaticoduodenal a.,
first jejunal branch from the superior mesenteric artery
What are the characteristics of jejunum?
Larger and thicker walls then ileum, prominent folds that circle the lumen = plicae circulates; less promiment arterial arcades and longer vasa recta
Where is jejunum located?
In the left upper quadrant - left hypochondrium
What is the blood supply of jejunum?
Jejunal arteries - from superior mesenteric artery
Where is Ileum located?
In the right iliac region
What are the characteristics of ileum
Thinner walls, fewer less prominent plicae circulares, shorter vasa recta, more mesenteric fat and arterial arcades, Peyer’s patches
Where does the ileum open to?
To the large intestine where cecum and ascending colon join together
Describe the ileocecal folds
Surround the iliac opening, 2 flaps projecting into the lumen, come together at the ends to form ridges, musculature continues into the flap to make a sphincter, controls reflux and regulates passage into the cecum
Describe the blood supply of ileum
Ileal arteries from the superior mesenteric artery, ileal branch from the ileocolic artery
Describe the microstructure of small intestine
Mucosa and submucosa are arranged into plicae circulares/valves of Kerckring, mucosal surface is made up of villi and the surface of columnar enterocytesis covered with microvilli
Where does the muscularis mucosae lie in the small intestine?
Beneath the mucosal crytps, separating mucosa from submucosa
How is the muscle organised within the muscularis of the small intestine?
Inner circular layer and outer longitudinal layer
What covers the peritoneal aspect of the muscularis of small intestine?
Loose collagenous serosa which is lined by mesothelium
What are Peyer’s patches and where they are found?
Lymphoid aggregations within the lamina propria, mostly in ileum
What are Brunner’s glands and where they are found?
Occupy entire submucosa and some in lamina propria mainly in duodenum, secrete alkaline mucins into the lumen of the small into the base of mucosal crypts
What is the epithelium of the small intestine
Villi lined by simple columnar epithelium continuous with the epithelium of the crypts
What are the cell types found in the small intestine?
Enterocytes, goblet cells, paneth cells, neuroendorine cells, stem cells, Intraepithelial lymphocytes, plasma cells
Describe enterocytes of the small intestine
Tall columnar cells, most numerous and main absorptive cells, have surface microvilli making up the brush border, contain large no of free ribosomes and mitochondria; 3-5 days lifespan
Describe the goblet cells within the small intestine
Scattered among enterocytes, produce mucins for lubrication and protection, 3-5 days lifespan
Describe the Paneth cells of the small intestine
At the base of the crypts, distinguished by their prominent eosinophilic apical granules, defensive function, contain antimicrobial peptides and protective enzymes like lysozyme and phospholipase A, weeks life span
Describe the neuroendocrine cells of the small intestine
Produce locally acting hormones that regulate gastrointestinal motility and secretion, different type for different hormone: secretin, somatostatin, serotonin
Describe the stem cells of the small intestine
At the base of the crypts, can differentiate into all of the cell types
Describe the intraepithelial lymphocytes of the small intestine
Mostly T cells, defense against invasive organisms
Describe the plasma cells of the small intestine
In the villous core, secrete IgA into the intestinal lumen by transcytosis
What is transcytosis?
Endocytosis with transfer to the extracellular fluid at the base of the cell
What is contained within the lamina propria of the small intestine
At core of each villus, contains rich vascular and lymphatic network - lacteal
What covers the surface of the microvilli?
Thick glycocalyx to aid absorption of pancreatic digestine enzymes and mucous layer
What type of cytoskeleton supports the microvilli?
Microfilament cytoskeleton
What is the basal lamina densa of an enterocyte like?
Discontinuous
What is found in the crypts of Lieberkuhn?
Mostly stem cells
What is the function of endocrine pancreas?
To secrete glucagon, insulin, somatostatin and pancreatic polypeptide
Name and describe the cells that produce glucagon
Alpha cells, 20% of each islet; low blood glucose stimulates release of glucagon
What cells produce insulin and what percentage of the islet do they make?
Beta cells, 75%
Describe characteristics of delta cells
4% of the islet, secrete somatostatin (also released by hypothalamus, stomach and intestine)
What is the role of somatostatin?
Inhibiting hormone - pancreatic somatostatin inhibits the release of both glucagon and insulin
Describe the characteristics of a PP cell
1% of islet cells, secretes pancreatic polypeptide hormone, role in appetite and regulation of pancreatic secretions
Describe the secretion s of acinar pancreatic cells
Secrete the inactive forms of the enzymes trypsin, chymotrypsin and carboxylpeptidases; active amylase, lipase, cholesterol esterase and phospholipase; trypsin inhibitor
What does the epithelial cells of the intercalated duct secrete?
Water and bicarbonate
What is a zymogen?
Inactive version of an enzyme
What triggers release of pancreatic enzymes?
Vagal stimulation (Ach release onto the acinar cells), Acidic gastric chyme which stimulates release of secreting and cholecystokinin - these then act on acinar cells and intercalated duct cells
What stimulates the pancreas to release bicarbonate ions and water?
Secretin
Name the enzymes that aid digestion of carbohydrates
Pancreatic and salivary amylase, lactase, sucrase, maltase, alpha-dextrinase
What is the role of pancreatic amylase
More powerful than salivary amylase, converts all carbohydrates to maltose and/or other small glucose polymers within 15 to 30 minutes
What are the common features of the intestinal epithelial enzymes?
Hydrolysis of disaccharides and polymers to monosaccharides, on the microvilli of enterocytes make up the brush border
What are the properties of lactase?
Splits lactose into glucose and galactose
What are the properties of sucrase?
Splits sucrose into fructose and glucose
What are the properties of maltase?
Splits maltose and glucose polymers to glucose
What are the properties of alpha-dextrinase?
Splits maltose and glucose polymers into glucose
How are glucose and galactose absorbed into the portal blood?
By sodium co-transport mechanism; Na+ is actively transported out of the enterocyte to blood which depletes the enterocyte of Na+ and the cell activates the secondary active transport, Na+ combines with transport protein at the lumen and once it also combines with glucose it is transported into the enterocyte, facilitated diffusion gets glucose from the cell to blood
How is fructose absorbed into the portal blood?
By facilitated diffusion and after entering the cell becomes phosphorylated and converted to glucose
Where does digestion of proteins occur?
Mostly in duodenum and jejunum, but begins in the stomach
What are the major pancreatic proteolytic enzymes?
Trypsin, chymotripsin, carboxypolypeptidase, elastase
What is the role of peptidases?
Aminopolypeptidases and dipeptidases on the brush border broke proteins further down
Describe the absorption of protein in the small intestine
Only aa, di and tripeptides are transported by sodium co-transporter, some amino acids are transported by faciliated diffusion
How do proteins move from enterocyte to blood?
Have to be broken down by specific peptidases into amino acids which than diffuse into the blood stream
Outline the digestion of fats in the small intestine
Emulsification by bile acids and lecithin, triglyceride digestion by pancreatic and enteric lipase, micelles formation by bile salts
What are the enzymes that digest cholesterol and phospholipids?
Cholester ester hydrolase, phospholipase A2
How are fats absorbed?
Micelles move to the brush border where they dissolve and its components dissolve across the plasma membrane, inside the cell the lipids are taken up by smooth endoplasmic reticulum and converted to new triglycerides, released as chylomicrons
How is water absorbed?
By osmosis between tight junctions and through the cells and creates flow of fluid
How is sodium absorbed in the small intestine?
By active transport (sodium-glucose co-transporter, sodium-amino acid co-transporter, sodium-hydrogen exchanger), then actively exported out of the cell, chloride ions are passively drag with sodium
What is aldosterone enhancement in the small intestine?
In response to dehydration released, acts to enhance enzymes and transporters to increase absorption of sodium, and thus also water and minerals
What are the 2 ways by which chloride ions can be absorbed?
Diffusion with Na+ and by membrane chloride-bicarbonate exchanger, exits the cell through chloride channels
How is bicarbonate absorbed in the small intestine?
Bicarbonate combines with H+ to form carbonic acid and then H20 and CO2, CO2 diffuses into the cell and into the blood, CO2 from blood is taken back in and converted to H+ and HCO3-
How are potassium, magnesium and phosphate absorbed?
Active transport, easier for monovalent than bivalent ions
How is calcium absorbed?
By Calcium-stimulated ATPase and Calcium-binding protein (calbindin) - controlled by PTH and vit D
List at least 5 causes of chronic pancreatitis
Alcohol, Chronic kidney disease, recurrent acute pancreatitis, hypercalcaemia, autoimmune, obstructive, tropical, hereditary: cystic fibrosis, trypsinogen and inhibitory protein defects
What type of pain is typical in chronic pancreatitis?
Epigastric pain radiating towards the back, episodic pattern, short periods of severe pain or chronic pain, increased after alcohol or fatty meal consumption
What are the signs and symptoms of chronic pancreatitis?
Pain, anorexia, weight loss, diabetes, exocrine insufficiency, jaundice
Define chronic pancreatitis
Long standing inflammation of the pancrea
List the initial investigations for chronic pancreatitis
Transabdominal ultrasound
List the further assessments for chronic pancreatits
Contrast-enhanced CT scanning (can see pancreatic calcification and dilated ducts) MRI with MRCP Serum amylase and lipase Serum IgM levels Faecal elastase Gene mutation analysis Endoscopic ultrasound
Describe the pathogenesis of chronic pancreatitis
Increase in activated trypsin within the pancreas, this leads to precipitation of proteins and plug formation; the plug is a nidus for calcification and causes ductal obstruction; leading to ductal hypertension and further damage
What are the 2 possible ways of increase in activated trypsin in pancreas during chronic pancreatitis?
- increased/premature activation of trypsinogen to trypsin
2. impaired inactivation/clearance of the activated enzyme from the pancreas
What are the main histological changes in chronic pancreatitis?
Loss of acini and replacement by fibrosis, Islets of Langerhans may or may not be destroyed
Name genes that can be related to chronic pancreatitis
PRS1 gene (encodes trypsinogen) Calcium-sensing receptor (role in trypsinogen activation, alcohol interaction) SPINK-1 (serine protease inhibitor) Cystic fibrosis transmembrane conductance regulator - CTFR (bicarbonate secretions which flush activated trypsin to duodenum)
Describe type 1 autoimmune chronic pancreatitis
Middle-aged men, associated with raised serum and tissue levels of IgG4, may be independent from trypsin pathways; other organs involved: billiary tree, thyroid, salivary gland and renal tissues
Describe type 2 autoimmune chronic pancreatitis
Early in mid-life, equal sex distribution, no autoimmune IgG4-positive cells, 30% of cases associated with inflammatory bowel disease
Describe the management of chronic pancreatitis
No treatment mostly symptom management:
Abdominal pain - NSAIDs and an opiate (tramadol), tricyclic antidepressants (amitriptyline), pregabalin; extracorporeal shock wave lithotripsy to fragment stones
What are the surgical treatments for chronic pancreatitis?
Duct drainage and partial resection of the pancreas
How do you manage malabsorption in chronic pancreatitis?
Pancreatic enzyme supplements in the form of microspheres, plus and acid suppressor like H2 receptor antagonist of proton pump inhibitor
How do you manage autoimmune chronic pancreatitis?
Glucocorticoid therapy and azathioprine for relapses
How should the diet be modified in chronic pancreatitis?
Abstain from alcohol, smoking and greasy/fried foods; drink plenty of fluids and eat high vitamin low fat diet
