Digestive Flashcards
1
Q
What are the two different ways of dividing the abdomen?
A
Quadrants: Right upper, left upper, left lower, right lower
9 Squares: Right hypochondrial, epigastric, left hypochondrial, right flank, umbilical region, left flank, right groin, pubic region, left groin
2
Q
What are the layers of the abdominal wall (superficial to deep)?
A
Skin Camper's fascia (fatty) Scarpa's fascia (membranous) External obliques Internal Obliques Transversus abdominis Transversalis fascia Extraperitoneal fascia Parietal peritoneum
3
Q
What are the muscles of the abdomen, their nerve supply and their actions?
A
- Rectus Abdominus: vertical fibre direction. Flex trunk, support abdomen. Supplied by ant. rami of thoracic spinal nerves
- External obliques: Inferomedial fibre direction. Flex trunk when both sides active, or bend trunk to same side when one side activated. Supplied by ant. rami of thoracic spinal nerves
- Internal obliques: Superomedial fibre direction. Flex trunk when both active, bend trunk when one active. Supplied by ant. rami of thoracic and some L1 spinal nerves
- Transversus abdominis: Transverse fibre direction. Support abdominal wall. Supplied by ant. rami of thoracic and some L1 spinal nerves.
4
Q
What is the rectus sheath?
A
In the upper 3/4 of the abdomen, the rectus sheath surrounds rectus abdominis- it comes off the medial sides of the other abdominal muscles
In the lower 1/4 of the abdomen, the rectus sheath only covers the front of the rectus abdominis, with the transversalis fascia and parietal peritoneum beneath.
The rectus sheath’s posterior covering stops around halfway between the umbilicus and the pubic bones, in order to prevent clamping of the inferior epigastric artery.
5
Q
What is the arterial, nervous and venous supply of the abdomen?
A
Arterial:
- Superior epigastric (from int. thoracic) and inf. epigastric (from ext. iliac). These run benath the rectus abdominis muscle on the transverse fascia and within the rectus sheath, to anastomose.
Venous:
Thoracoepigastric veins drain to axillary vein
Superficial epigastric veins drain to femoral vein
Nervous:
Lat. and ant. cutaneous branches of T7-12, as well as the hypogastric nerve from L1
6
Q
What are the dermatomes of the torso?
A
T10 covers the navel
T9/8/7 extend upwards, and T11/12/L1 extend downwards in bands.
7
Q
What is the lymphatic drainage of the abdomen?
A
The two upper quadrants drain superolaterally into the anterior axillary nodes
The two lower quadrands drain inferolaterally into the superior inguinal nodes
The posterior torsos drain into the posterior axillary nodes.
8
Q
What is the peritoneum and mesentery, and how are they sensitive?
A
It resembles a fist in a balloon- visceral covers the fist, with the space between, and then the outer border if the parietal peritoneum. Parietal peritoneum senses pain, touch, temperature and pressure. It is supplied by the somatic nerves, the phrenic nerve and the obturator nerve.
The visceral peritoneum and mesentery are sensitive to to stretch by the ANS.
9
Q
What is the difference between intra- and retro-peritoneal structures?
A
Intraperitoneal structures are completes wrapped in visceral peritoneum and are suspended by mesentery
Retroperitoneal structures are between the peritoneum and the body wall, without a mesentery. (pancreas, kidneys, distal duodenum, asc/desc colon and upper 2/3 of rectum.
10
Q
What is the difference between the greater and lesser sacs?
A
The greater sac is the peritoneal cavity proper, while the lesser sac is located behind the lesser omentum and the stomach, formed due to rotation of the foregut
The omental foramen leads into the lesser sac, as the lesser omentum has a free edge by the liver. The lesser sac is bounded posteriorly by the Inferior vena cava.
11
Q
What are the paracolic gutters?
A
They are sulci lateral to the ascending and descending colon, in front of the parietal peritoneum. They create a pathway for fluid to migrate around the abdomen. The right one is more important as it’s larger and continuous with the lesser sac.
These are clinically significant as they have a role in pain referral depending on where fluid migrates to.
12
Q
What are the structures in the fore, mid and hindgut?
A
Foregut: Pharynx, lower resp. tract, oesophagus, stomach, liver, biliary apparatus, pancreas, proximal half duodenum
Midgut: Distal half duodenum, jejunum, ileum, caecum, appendix, ascending and prox. 2/3 transverse colon
Hindgut: Distal 1/3 transverse colon, descending and sigmoid colon, rectum, 2/3 anal canal.
13
Q
What germ layer does the gut develop from and how does the gut fold to create the tubes?
A
Endoderm.
Lateral and longitudinal folding cause the formation of a gut tube, while the fore and hindgut close off and the midgut remains open to the yolk sac. Eventually the orophangeal and anal membranes rupture and the tube is complete
The lumen of the tube is initially open, but then plugs with epithelilum and is then recanalized
14
Q
What is the arterial supply of the embryonic gut and how does this help in classifying it?
A
Foregut: celiac trunk
Midgut: Superior mesenteric artery
Hindgut: Inferior mesenteric artery
15
Q
How does the oesophagus form?
A
Initially is is one tube with the trachea, but it partitions and rapidly elongates. However, there can be fistula (connection) and atresia (blockage) between them if part of the esophagus partitions and a lower part forms a fistula with the trachea.
There can also be hiatal hernia, where the esophagus fails to lengthen and pulls the stomach into the thorax
16
Q
How does the stomach form? 3 stages. What are some possible malformations/
A
- Foregut tube starts to dilate
- Continues to dilate, rotation 90 degrees clockwise (long axis). Anterior mesogastrium moves right, post. to left. Note that the posterior mesogastrium begins to hang down under gravity, and the two borders fuse to form the greater omentum
- Continues to dilate. Rotates 90 degrees coronally, so that the right boundry makes the lesser curvature and the left boundary becomes the greater curvature.
Hypertrophic pyloric stenosis can occur when the pylorus is much thicker than usual, blocking chyme’s exit into the duodenum, resulting in bile-less vomit.
17
Q
How does the liver, bile duct and pancreas form?
A
Hepatic diverticulum divides into 2: Larger sup. structure becomes liver, smaller inf. structure becomes biliary apparatus.
The bile duct is attached to the vent. duodenum,, although it moves posteriorly as the duodenum rotates.
The pancreas develops between both mesogastric layers- initially there is a bud on the dorsal and ventral mesogastrium. As the biliary tree rotates dorsally, the ventral fuses with the dorsal and they both anastomose with one pancreatic duct remaining (sometimes an accessory duct remains betwen the original dorsal pancreas and the duodenum)
The liver is then attached to the ventral parietal peritoneum by the falciform ligament. The lesser omentum connects liver and stomach, the gastrolienal ligament connects stomach and spleen, and the lienorenal ligament connects sleep with kidney.
18
Q
How does the midgut form? What are some possible congenital malformations?
A
Initially it is U shaped, with crainial and caudal limbs either side of the SMA. It then herniates into the umbilical cord as it grows, before the midgut loop rotates counterclockwise through to 270 degrees. Eventually the herniation retracts and the cecum and appendix drop into lower abdomen.
It is possible for the gut to remain herniated into the the place the umbilical cord used to be if the cord doesn’t close properly
There can also be meckel’s diverticulum, where the navel is open to the gut tube.
19
Q
How does the hindgut form? What are some possible malformations?
A
- Initially there is the cloaca, which connects the anal and urinary canals. Eventually a urorectal septum extens between the two, separating them
The upper 2/3 of the anal canal is hindgut, receiving blood supply from IMA, whereas the lower 1/3 comes from proctoderm. - Can have hirschprung’s disease, where some colon is dilated and cannot relax for peristalsis.
- Can have imperforated anus
- Can have rectal atresia- blockage between the anal canal and rectum, with possible fistulas to urethra, bladder or vagina
20
Q
How does nutrition affect health?
A
- Affects health outcomes very strongly- impacts progression and treatment of chronic disease.
21
Q
What factors influence our nutrition choices?
A
Components of our environment- food production, distribution, preparation, labels, our own perception of meals
The person themselves- our genetics, physiology, lifestyle and needs
We are also affected by our food due to the carbs, proteins, fats, vitamins and minerals we receive.
22
Q
What is the difference between nutrition for a population and nutrition for a person?
A
Nutrition goals for a population are based on disease statistics, average current diets, as well as widely acceptable guidelines (one size fits all)
Nutritional goals for a person will differ as everybody’s lifestyle, metabolism and genes are different.
There are differences for everyone in age, stage and physiology.
23
Q
What is a DALY?
A
Daly = Disability adjusted life year.
It is calculated as years of life lost + years of life with a disability.
24
Q
What are the main 4 suggestions of the MoH food and nutrition guidelines?
A
- Enjoy a variety of nutritious foods every day: Plenty of fruit & vege. Plenty of breads and cereals (wholegrain). Some milk and milk products, low and reduced fat. Some legumes, nuts, seeds, eggs, poultry, red meat with fat removed.
- Choose and prepare foods and drinks with minimal added (sat) fat, low in salt (iodised salt preferable) and with little added sugar
- Make plain water your first choice
- If you drink alcohol, keep intake low.
25
Why is the recommendation to eat a variety of nutritious foods in place?
- Veges and fruit provide vit. C, A, K, phytochemicals, minerals, fibre
- Wholegrains contain fibre, vit. B, E, minerals, carbs, protein, phytochemicals, protect against cancers, obesity, CVD
- Dairy protects against osteoporosis
- Legumes contain protein, minerals, vit. A, E, fatty acids- protect against cancer, diabetes, CVD
26
Why is the recommendation to prepare your own food/drink or to choose carefully in place?
- Difference in energy density of preprepared foods- more easy to overeat
- NaCl is bad for hearts, kidneys, blood vessels
27
What are the branches of the celiac artery?
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Left Gastric (runs superiorly)
Common Hepatic (runs right)
Splenic (runs left)
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28
Where do the main abdominal arteries branch from the aorta?
Celiac- upper border of L1
SMA- L1
IMA- L3
29
What is the arterial, nervous, venous, and lymphatic supply of the foregut?
Artery- coeliac axis
Veins- Portal vein
Lymph- Pre-aortic nodes at T12 (pre-aortic)
Nervous- Coeliac plexus (T12)
30
What is the overall anatomy of the stomach? What is its blood supply?
The fundus of the stomach is located at aprox. rib 5/6, with the oesophagus coming in at the edges of costal cartilage 7 & 8. The distal end lies at the L1 vertebral level.
The stomach has multiple layers of muscle- outer longitudinal, middle circular, and inner oblique layers.
The lesser curvature is supplied by left and right gastric arteries, with the greater curvature supplied by left and right gastro-omental arteries, from the splenic and ch arteries respectively
The fundus is supplied by the short gastric artery, a banch of the splenic artery.
31
What is the anatomy of the duodenum, and what is its blood, lymph, venous and nerve supply?
It is divided into 4 parts:
1: superior (trans-pyloric)
2: Descending
3: Inferior
4: Ascending to duodenojejunal flexure.
part 1 is intraperitoneal, part 2-4 are retroperitoneal.
Arterial supply: Part coeliac, part SMA- sup half- superior pancreaticoduodenal artery. inferior half: Inferior pancreaticoduodenal artery.
Nervous: Sup: Coeliac plexus (T12) Inf: SMPlexus, L1
Venous: Sup: Portal vein. Inf: SMVein (then portal)
Lymph: Sup: Pre-aortic coeliac nodes (T12) Inf: Pre-aortic SMNodes (L1)
32
What is the neurovascular and lymph supply of the midgut? How is it divided, identified and how does it sit?
Supplied by SMA, SMV, SMP (L1) and SMN (L1)
Divided into Jejunum (identifiable by 1-2 arcades with long branches) and ileum (identifiable by multiple arcades with short branches)
Suspended by mesentery to allow ingress/egress of neurovascular structures.
33
What is the NV/lymph supply of the midgut small intestine?
- Jejunal and ileal arteries
- SMPlexus
- SMVein
- SMNodes
34
What is the meaning of the flexures in the large intestine? Where is the transition from midgut to hindgut?
- Hepatic flexure is related to the liver (RHS)
- Splenic flexure is related to the spleen (LHS)
- Transition occurs 2/3 along the transverse colon
35
What is the structure and function of the large intestine?
```
Has haustrae (sacculations of wall), appendices epiploicae (fatty tags), teniae coli (long. muscles continuous with small intestine muscles) and an appendix.
Function is to absorb water and electrolytes, and store undigested material before its expulsion.
The large intestine is found in almost all 9 parts of the abdomen (except the umbilical)
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36
What are the different arterial supplies of the large intestine?
- Caecum and appendix- caecal and appendicular arteries
- Ascending colon- right colic artery
- Proximal 2/3 trans. colon- middle colic & marginal artery
- Distal 1/3 trans colon- marginal and left colic arteries
- Descending colon- left colic artery
- Sigmoid colon- sigmoid artery
NB marginal artery is anastomotic point between mid and hindgut- arteries after this come from L3 and so do veins, lymph etc.
37
What is the structure, function and supply of the rectum?
- Rectum pierces pelvic diaphragm to become anal canal. It is best sectioned into 3 parts:
- Sup. 1/3 is intraperitoneal, supplied by sup. rectal artery (IMA), drained by sup. rectal vein, supplied by IMPlexus and IMNodes.
- Mid 1/3 is retroperitoneal & supplied by middle rectal branch of internal iliac artery & drained by mid. rectal vein (goes to common iliac and IVC)
- Inf. 1/3 is infraperitoneal & supplied by inferior rectal branch of internal pudendal artery, drained by inf. rectal vein (goes to common iliac and IVC)
Both are supplied by inf/sup hypogastric nerve plexus and have lymph to internal iliac nodes
38
What is the portal system?
The Splenic and SM veins drain into the portal vein, going to the liver. The IMV joins the splenic vein beforehand, to prevent it being squished. The portal vein is formed at level L1 in the trans-pyloric plane.
39
What is the nervous supply of the gut?
- Parasymp- vagus nerve, pelvic splanchnic nerves (S2-4)
- Sympathetic- ganglion chain using thoracic, lumbar and sacral splanchnic nerves- but only exiting the chain from levels T5-L2.
40
What is the autonomic supply of the gut regions?
F: Greater splanchnic nerve (T5-9), Vagus nerve
M: Lesser Splanchnic nerve (T10-11), Vagus nerve
H: Lumbar/Sacral splanchnic nerve (L1-2), Pelvic splanchnic nerve (S2-4)
41
Why is abdominal pain referred and where do the different regions refer pain to?
Pain is referred, as the visceral afferents return to the plexus and chain before being sent up the spinal cord. The brain doesn't know where it's coming from as it thinks it's a somatic nerve- just uses the dermatomes of the spinal nerves to refer it and diffuse the pain between the contributers.
Foregut- pain to epigastric region
Midgut- pain to umbilical region
Hindgut- pain to suprapubic region
42
What is the pathology of appendicitis pain referral?
Initially, broad diffused pain from midgut (referred to to umbilical region).
Eventually, appendix gets so large that it touches the parietal peritoneum and the nociceptors for that specific dermatome ar initiated as parietal peritoneum has somatic sensory supply- pain is low acute in the right inguinal region.
43
What are the general layers of the gut tube and what are their structures and functions?
Luminal: Mucosa. Consists of:
- Epithelium- offers protection (physical or chemical), secretion and absorption. It receives its nutrients via diffusion from the lamina propria
- Lamina Propria- supports the epithelium, and is the functional layer- has blood vessels, lymphs and nerves. It consists of connective tissue fibres (collagen etc)
- Muscularis mucosae: Inner circular/outer longitudinal layers of muscle that produce micro-movement of the mucosa separate to the muscularis externa.
Submucosa: Like lamina propria, but larger scale
Muscularis externa: Responsible for coordinated contraction and relaxation of inner circular and outer longitudinal layers- peristalsis. Rezuires narrowing and shortening of tube. Stomach has 3 layers. Mostly all smooth muscle (apart from oesophagus- some skeletal)
Adventitia/serosa: Adventitia is outermost connective tissue when the structure touches other structures. Serosa is the visceral peritoneum, which covers the structure when it is only in contact with 'empty' space.
44
What is ascites and peritonitis?
Ascites- accumulation of fluid (peritoneal) causing abdominal swelling, pressure and distortion of organs
Peritonitis- physical, chemical, bacterial trauma to peritoneum causes inflammation
45
What are the different types of salivary secretory cells and what are their structures and functions?
Serous acinus- contains myoepithelial cells, which have contractile properties for squeezing out secretions. They contain zymogens, or pre-enzymes, which form the enzyme amylase. They produce watery secretions
Mucous acunus- cells resemble goblet cells, with nuclei squished along the bottom to make room for mucus granules. Produces mucus to lubricate.
46
What is special about the ducts of the salivary glands?
They appear striated, as they are packed with mitochondria. This is to help them with active transport, of Na+ and Cl- in, and HCO3- and K+ out, forming an effective buffer.
47
What are the salivary glands, and what cell types do they have?
Sublingual- mostly mucus
Submandibular- mixed
Parotid- mostly serous
48
What is the composition and function of saliva?
- 99% water
Also has some carb-rich glycoprotins called mucins: lubrication, protection from bacterial adhesion
Bicarbonate ions- counteract bacterial secretions, protect against acidity of vomit
Lysozyme- breaks bacterial cell walls
Lactoferrin- counteracts iron-dependent bacteria
Immunoglobulin A- counteracts general bacteria and viruses
Also some digestion through amylase (sugars), lipase (fatty acids), Haptocorrin (binds and protecte B12) and Kallikrein (a cascade to increase salivary blood flow)
49
What is the function of the oesophagus? What is unique about it?
Rapid transport of food to the stomach
Contains skeletal muscle in upper third for voluntary control of swallowing
Epithelium is thick and stratified squamous for sacrificial epthelium
Submucosa is loose to permit compression and expansion of main tube during swallowing
50
What are some problems that can occur with the oesophagus?
Oesophageal varices- liver cirrhosis can lead to portal backflow, so blood accumulates in the oesophageal arteries- can cause haemorrhage
Reflux oesophagitis- acid reflux causes damage to the oesophagus- loss of epithelia continuity and increased lymph tissue size. Can flow into barrett's oesophagus, where there is a semipermanent transition from squamous to glandular epithelium- this can also cause cancer
51
How can nutritional status be assessed?
- diagnosis, screening, intervention, monitoring, policy setting, programme evaluation and nutritional surveillance
52
Why is nutritional status important? How does it affect medicine?
1/3 patients admitted to hospital are malnourished, assoc. with higher morbidity, infections, complications, mortality, treatment requirements, longer hospital stays and greater cost, as well as lower healing, convalescence and quality of life.
We ask about it for past medical and family history, in terms of medications to prevent drug interation, a diet or social history, a systems review, during a physical exam, for laboratory evaluation, and as part of assessing and planning treatment.
53
What is the ABCDE of nutrition assessment?
A- Anthropometric (weight, height/arm span, circumferences, percentage weight loss, body composition, distribution of body fat)
B- Biochemistry- detects subclinical or marginal deficiencies, gives support to other data, gives response to supplementation, checks nutrients in blood or urine
C- Clinical- signs and symptoms, measurement of functional status and oral health, cognitive, drug use
D- Dietary evaluation- measure food and beverage intake compared to dietary requirements, food consumption patterns, supplement usage, feeding practices and food security. Compare to recommended dietary intakes, guidelines and plate/pyramid models
54
What are the methods of assessing diet?
Food history
Food frequency questionnaire
24 hour recall
Food records
55
What are the different methods of evaluating anthropometry?
BMI
Percentage age weight loss (Usual weight-current weight)/usual weight (x100)
Body composition- fat + lean tissue, cell mass + excell mass + fat, bone + protein + H2O + fat
Distribution of body fat- waist: hip ratio, waist circumference
56
What are the three phases of swallowing, and their descriptions?
Oral phase- voluntary, requiring soft palate elevation, and movement of the tongue posteriorly to prevent regurgitation. Has a prep phase (chewing, positioning bolus) and a transfer phase
Pharyngeal phase- Controlled reflexively, to protect the airway and any further propulsion. Involves elevation of larynx and closure of vocal cords to close mouth and airways (upper & lower)
Oesophageal phase- transfer of food bolus from UES to the LOS. Combines primary (initiated by swallowing) and secondary (reflexive- peristalsis from stretch)
57
How is swallowing controlled?
By both cortex and brainstem
| Swallowing centre receives input from psot. mouth and upper pharynx. Swallowing muscles innervated via cranial nerves
58
What are the oesophageal sphincters?
Upper- prevents entry of air into stomach and reflux into pharynx during peristalsis. Consists of cricopharyngeus, inf. pharyngeal constrictor and cervical oesophagus
Lower: near squamocolumnar junction, specialized smooth muscle, can relax transiently (regular intervals in upright position to release air from stomach)
59
How does peristalsis get innervated?
ANS innervation, from submucosal and myenteric plexuses
60
What is GORD, why does it occur and what happens?
Gastro-Oesophageal reflux disorder is the movement of gastric contents into the oesophagus, which erodes it. It occurs due to transient LOS relaxation. This can be due to a hypotensive muscle sphincter (drugs, food), a hiatus hernia (loss of sphincter support due to stomach herniation through the diaphragm) and impaired oesophageal peristalsis, reducing clearance.
It causes heartburn, regurgitation and a sour taste in the mouth- worse after lying down/eating
It can cause peptic stricture due to fibrosis, barrett's oesophagus and cancer
61
What is Barrett's oesophagus?
Formation of columnar epithelium in lieu of squamous epithelium within the oesophagus due to repeated acid exposure- secretes alkaline substances. This also increases the patient's risk of adenocarcinoma.
62
What are the two types of oesophageal cancer?
Adenocarcinoma- promoted by barretts, in LOS region
| Squamous cell carcinoma- caused by smoking, alcohol, diet- more likely proximal
63
What are some common structural disorders of the oesophagus?
Ring/Web- mucosal membrane found distally
Zenker's diverticulum- Excessive pressure on pharynx causes balooning, and trapping of food there
Stricture- narrowing of oesophagus due to fibrous scar formation
Oesophageal candidiasis- white plaques form on oesophagus
Ulcers
Eosinophilic oesophagitis- allergy mediated as eosinophils infiltrate it
64
What are some common motility disorders of the oesophagus?
- Dysphagia (difficult swallowing)
- Achalasia- degeneration of oesophageal nerves- loss of distal peristalsis, failure of LOS to relaw
- Diffuse oesophageal spasm: simultaneous onset of oesophateal contractions, can cause chest pain
- Nutcracker oesophagus- v. high amplitude contractions
- Scleroderma: Damage to submucosa, causing no movement of oesophagus- no peristalsis, no LOS tone, severe reflux
65
What are the main functions of the stomach?
Acts as a reservoir for food, and is able to release it in closely controlled bursts as chyme
Adjusts osmolarity of its contents before their release into the SI
Antrum is a sort of 'grinding mill' regulating particle size into the duodenum
Acid, IF, pepsinogen, mucus, prostaglandin, HCO3- secretion
66
How is gastric emptying usually controlled, and what can go wrong with it?
Controlled by feedback from the duodenum regarding its acidity, fats, amino acids and osmolarity.
It requires an intact antrum, pylorus and duodenum, as well as normal vagal and hormonal function
Rapid gastric emptying occurs typically after gastric surgery or when taking prokinetics.
This is largely due to a dilated duodenum & jejunum causing the presence of large, hyperosmolar food particles in the small bowel causing more chyme to be drawn into the duodenum, and more water, causing diarrhoea, vomiting, cramping with eating.
Delayed gastric emptying id due to deficiency in the vagal nerve. It causes a variable rate of glucose absorption and abdominal discomfort, as well as bloading and early satiety
67
What does gastric acid do? How is it regulated?
Gastric acid sterilizes the stomach (except H. pylori)
Denatures proteins
Helps with B12/Fe absorption
Regulaged by a negative feedback loop:
Acid is produced by parietal cells. Parietal cells are stimulated by ECL cells, which secrete histamine to activate parietal cells. These are stimulated by G cells which secrete gastrin. D cells secrete somatostatin to inhibit G cells, and they are stimulated by low pH.
Achlorhydria (low/absent gastric acid) can allow bacterial overgrowth, a decreased absorption of Fe, and increased infection risk.
ACh from the vagus nerve also stimulates parietal, ECL and G cells, which in turn is caused by stomach distension, as well as the sight, thought or smell of food.
68
What do the parietal cells do and how are they protected?
They produce acid by taking in Cl- from the blood in exchange for HCO3-, and sending out H+ in exchange for K+.
They are protected by HCO3- rich mucus on the surface of the stomach. These protect the gastric epithelium. If the mucus is not present, the stomach is exposed to its acid and ulcers can form. If it isn't replenished, healing said ulcers is also much harder
69
What can cause abnormal secretion of gastric acid?
Increased- Either H pylori in gastritis or gastrin producing tumors
Decreased- loss of parietal cells, as in pernicious anaemia, vagotomy or some drugs.
70
What is the role of CCK and secretin in digestion?
Both inhibit gastric acid secretion and gastric emptying
CCK releases pancreatic enzymes and bile
Secretin stimulates HCO3- from the pancreas and bile ducts
71
What is the pathology of a peptic ulcer? IE causes, transmission, effects, treatment, side effects
Caused by H pylori infection, which is acquired in childhood and leads to lifelong infection and chronic gastritis. It's associated with childhood living conditions
It is infected orally-orally, usually by sharing food
It typically infects the antrum, and is often asymptomatic. However, if the ulcer develops it forms a cavity due to the erosion of the mucosa- it can cause bleeding if it perfs a vessel. It presents as burning epigastric pain, worse during and after eating, as well as possible bleeding and upper digestive tract obstruction
Treated by eradicating with triple therapy antibiotics for 1 week, and has a low recurrence rate once successfully treated.
Can cause atrophic gastritis and achlorhydria, which can allow infection of bacteria and tumors to form.
72
What are the two types of gastric cancer?
Intestinal type is well differentiated cells with tubular pattern, more likely found in the antrum and associated with H.Pylori.
Diffuse type lack gland and have poor differentiation of cells, more likely associated with genetic factors
Patients present with discomfort, early satiety, pain after meals, anorexia and weight loss.
73
How is B12 absorbed in the body?
1. CBl protein in food comes from the mouth, bound to Hepatocorrin to protect it from the stomach acid.
2. CBl and HC are split in the duodenum
3. IF secreted by parietal cells binds with CBl and all travel to ileum
4. Taken up by receptors on the brush border of the ileum, and IF is released once they are in the cell
Then either: Transported via HC to the liver, where B12 is recycled in the bile via enterohepatic circulation
OR
CB takes it to cells where it is required for DNA synthesis
74
What is the pathology of Folate/B12 deficiency, and how can you tell these apart?
Both present as anaemia, with macrocytosis of RBCs, presenting as high mean cell volume. However, folate deficiency does not show degeneration of the spinal cord as B12 does.
Decreased B12 causes decreased methylation ability, resulting in decreased DNA reproduction- so cells with a high turnover will be negatively affected
75
What is required to absorb B12 and what test can you do to figure out where the issue is?
Requires- Acid to release CBl from food
- IF secretion from parietal cells
- Normal pancreatic secretion
- Normal ilial function
Can perform schilling test- give radioactive B12, and fill receptors by injecting normal B12 intramuscularly. Measure B12 in urine- not a stomach issue if B12 is bound to IF
If IF isn't normal, test for ileal dysfunction by repeating with oral IF and seeing if it's fixed by this
76
How do you determine whether B12 deficiency is due to an autoimmune disorder or not?
Most likely pernicious anaemia/autoimmune gastritis:
- Check for antibodies to parietal cells and intrinsic factor, for a low acid output (visible if gastrin is high) and evidence of other autoimmune diseases
77
How do you treat B12 deficiency?
Needs replacement in high doses- 1000ug every week for 4-6 weeks.
If not a dietary depletion, then needs maintenance of 1000ug every three months
78
Why does terminal ileal resection cause B12 deficiency?
Loss of ileal receptors- Failure to absorb B12, bile salts
| Bile salts can also irritate the colon and impair the absorption of fats
79
Why does partial gastrectomy cause B12 deficiency?
Loss of gastric acid secretion so B12 in food can't be released
Atrophic gastritis (bile reflux)- causes loss of parietal cells and IF secretion
Failure of normal stimulation of pancreas
80
What are the key functions of fats?
Energy/fuel source
Required for fat-soluble vitamin transfer
Provide essential fatty acids
Important for insulation/protection
81
What are the different types of fats and their structures?
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Triglycerides (fatty acids)
- Polyunsaturated (many double bonds)
- Monounsaturated (one double bond)
- Saturated (no double bonds
- Trans (previous double bonds filled)
Unsaturated fats are liquid at room temperature, with mono less susceptible to spoilage. Saturated fats are always at room temperature
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Sterols
- only found in animal foods. Multiple ring structure
Create bile acids, sex and adrenal hormones, vit D and cell membranes
The liver produces 80% of our cholesterol per day, and a buildup in our arteries causes atherosclerosis.
82
What is the process of fat digestion?
Lingual lipase from mouth begins digesting fats
Gastric lipase hydrolyzes a small amount of fat in the stomach
Bile emulsifies the fat, which is then further split into monoglycerides, glycerol and fatty acids by pangreatic and intestinal lipase
In the large intestine, some fat and cholesterol exit via feces.
83
How is fat transported?
Small molecules cause micelles bind to large lipids to transport them across the apical membranes of the cells. They are then repackaged into chylomicrons, which are small and dense. They run in the bloodstream, giving off fatty acids to cells that need them, before remnant chylomicrons are endocytosed by the liver.
From here it can be stored or send out via:
Reverse transport pathway: HDL produced in liver, deliver cholesterol to tissues needing it
Endogenous Pathway: LDL produced in liver, drop off fatty acid and are taken back up by LDL receptors
84
What are the recommendations regarding fat in the diet?
Limit sat/trans fats to less than 10% of daily energy intake
Fats as a whole should make up approx. 20-35% of energy intake
Select low fat options and lean option, and minimize processed fats.
85
What is the structure of a chylomicron compared to other lipoproteins?
Chylomicrons contain a large amount of triglycerides, with barely anything else
VLDL contain mainly triglycerides
LDL contain mainly cholesterol
HDL contain mainly protein
86
What are the adaptations of the small intestine to maximise surface area?
Have plicae circularie- macroscopic folds in the wall of the intestine
Plicae are covered with villi, which in turn are covered in microvilli
87
What are the features of a villus and how are they adapted for absorption?
Villi have intestinal glands (crypts of lieberkuhn) beneath them, and project into the lumen of the intestine
The contain within them a lacteal, with smooth muscle fibres from the muscularis mucosae surrounding it in order to milk the lacteal.
There is also a small capillary with arteriole and venule (to the portal vein) within each villus.
In the elderly, decreased blood circulation can lead to malabsorption and potentially malnutrition as a consequence of this.
88
What are the main epithelial cells found within the small intestine? What are their functions?
Columnar absorptive cells (enterocytes)- their cell membranes contain enzymes that can be digestive (eg. glycosidases) or that activate other enzymes- eg. enterokinases or enteropepsins.
They have microvilli, and are covered with glycocalyx- this is enriched with glycoproteins, and acidic mucopolysaccharides. It forms a selective barrier which attracts desirable things (ie what its enzymes work on) and repels unwanted things
The actin within the cel is connected to its cytoskeleton, which helps to move the microvilli in a wave formation along with the villi themselves.
Goblet cells: Secrete mucus
Enteroendogrine cells- secrete CCK, sterotonin and somatostatin
Undifferentiated cells- generates new epithelium
Paneth cells- Mainly defence, through TNF and lysozymes
89
What are the roles of CCK, Serotonin and somatostatin in the small intestine?
CCK: Give negative feedback to stomach, reducing gastrin
Promotes enzyme release from the pancreas
Causes gall bladder to contract and release bile
Secretin- give negative feedback to stomach to decrease gastrin. Causes ductal cells in biliary tree to make and secrete HCO3-
Somatostain- causes decreased gastrin, increases absorption and increases smooth muscle contraction in the small intestine.
90
What are the special features of each section of small intestine?
Duodenum: C shaped, 25cm. Contains submucosal glands, which secrete HCO3- rich mucus, called brunner's glands. They decrease in number throughout the small intestine.
Jejunum: 2.5m, suspended by mesentery. Have increased numbers of plicae for absorbing and digesting
Ileum: 3.5m, with very large lymphatic aggregates which appear red under the naked eye (called peyer's patches). Main function is defense, as there are many bacteria next door in the Large intestine.
91
What is the structure and function of the lining of the large intestine?
Mucosa is smooth, with no villi, but has mucosal glands. These contain mainly columnar absorptive cells with a brush border (for vitamins, water and electrolytes) and goblet cells, secreting mucus for lubrication.
The lamina propria contains many lymphatic nodules
Muscularis externa contains outer longitudinal layer in three distinct bands (teniae coli), which segment the colon into haustra (for different rates of absorption and segmentation)
92
What is the transition in muscle and epithelium in the rectum/anus?
Epithelium moves from columnar epithelium to stratified squamous at the transverse folds
The internal anal sphincter is smooth muscle, while the external is skeletal muscle.
93
How do the rates of and movements of differentiating cells change in the different gastric regions?
Oesophagus: cells from basal parts move upwards, changing over days
Stomach: cells move upwards over days, and downwards over weeks/months
Small intestine: cells move upwards over days, and downwards over weeks/months
Large intestine: cells move upwards to replace others over days
94
What are carbohydrates used for?
Energy stores
Prevention of ketosis
As ribose and deoxyribose sugars
Cellulose (plant cell walls)
95
What are the different sorts of carbohydrate, and where are they found?
Monosaccharides- single sugar rings
Glucose (main energy source) Galactose (dairy) and fructose (fruit and vegetables)
Disaccharides: double sugar rings.
Lactose (glucose with galactose) found as the only carbohydrate in pure dairy
Maltose (2glucose)
Sucrose (glucose with fructose) found as table sugar
Starch Polysaccharides- made of hundreds/thousands of monosaccharides. Can be branched or unbranched, amylose (no branches), amylopectin (long and branched) (not water soluble- rice, potatoes, wheat), glycogen (major molecule stored in liver)
Non-Starch polysaccharides- dietary fibre. Can be soluble (dissolves in water, fermentable) or insoluble (does not dissolve, not fermented)
96
How are carbohydrates digested?
1. Salivary amylase breaks starch into small polysaccharides and maltose
2. The stomach acidity causes amylase to denature. It also mechanically breaks down food.
3. Starch is broken down by pancreatic amylase into small polysaccharides and maltose. Its further breakdown is carried out by enzymes on the brush border of small intestine enterocytes. The enzymes have specific names for the carbohydrate they break down- eg. maltase breaks down maltose.
4. Clucose and galactose are absorbed via Na+- co transporters, while fructose is absorbed by facilitated diffusion. They then are transferred from the cell to the capillaries.
97
What is ketosis and what do carbohydrates have to do with nutrition?
When carbohydrate intake is limited, protein is converted to glucose, and fat stores to ketones (alternative energy)- however, if they accumulate in the blood it causes ketosis, disturbing the body's acid-base balance.
Carbohydrates should comprise about 40-65% of our energy intake, and only 10-15% of this should be simple sugars
98
What do sugars and dietary fibre have to do with health?
Sugars often are added to foods to sweeten them, although they aren't always obvious. Too much sugar can cause fluctuations in insulin and energy, as well as hunger.
Dietary fibre assists in body weight maintenance. Insoluble fibre accumulates water, providing mass to the faeces, and softening them. It also increases transfer time and decreases chance of haemorrhoids (due to excessive strain)
Soluble fibre inhibits absorption of cholesterol and bile acids from the small intestine. They also bind to fatty acids, prolong stomach emptying, and regulate blood sugar.
99
How does insulin vary depending on the carbohydrate source?
If you eat simple sugars, your glucose skyrockets and then plummets, as does the insulin levels.
Starchy sugars cause a slower ascent and descent as well as plateau, causing less hunger and less fluctuation in insulin
(NB insulin shoves glucose into cells, glucagon converts glycogen from the liver into glucose)
100
What are proteins used for?
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Building materials
Enzymes
Hormones
Fluid balance/ Acid-base regulators
Transporters
Antibodies
Energy source
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101
What are essential amino acids and why are they essential? How can this change?
They are essential for survival
| The number may change, as under certain environmental circumstances some may become essential
102
What are our dietary requirements for protein and how do we know if these are high quality?
Protein should make up 12-25% of our energy intake or .84g/kg (male) and .75g/kg (female) per day
High quality proteins are defined as providing enough of all ess. AA. They are graded based on two factors
- Digestibility- depends on source (animal better than plant) and other foods eaten with it. Eg. vegetarians should eat complimentary proteins- they come from multiple sources to cover all EAAs
- Amino acid composition- how many EAA, and enough nitrogen-containing amino groups for synthesis of others
103
How are proteins digested?
1. Chewed up in the mouth
2. HCl and pepsin begin to hydrolyse proteins into smaller polypeptides in stomach
3. Endopeptidases (trypsin, chymotripsin, elastase) are activated in small intestine, as a sort of cascade begun by the activation of trypsinogen by enteropeptidase. This also allows for a negative feedback loop. Carboxypeptidases A and B are also involved, and they all work together to degrade proteins into tri/di/ amino acids.
These are further degraded into amino acids by peptidases on the brush border of enterocytes
4. They are transported into the cell by Na+ /amino acid co-transporters, or Na+ di/tripeptide transporters (to be broken down in the cell_
104
What is nitrogen balance and how can this differ?
Normally, we expect nitrogen equilibrium: the amount of protein the body uses is the same amount as what it excretes.
Negative nitrogen balance occurs when the body excretes more nitrogen than it uses up- the body is losing nitrogen. This occurs when degradation of protein is greater than synthesis- eg. immediately after decreased protein intake, during starvation, trauma, illness, cancers, lactation.
Positive nitrogen balance occurs when the body is using more nitrogen than it excretes- a net gain of nitrogen. This occurs when synthesis of proteins is greater than protein degradation. It can be caused immediately after increased protein intake, during growth, pregnancy, and recovery from trauma.
105
What is the function, structure and gross anatomy of the liver?
It is the 2nd largest organ in the body, and is responsible for detoxification of blood, carb and glucose regulation, bile drainage, blood filtration, synthesis and storage of acids, proteins, fats and vitamins.
Therefore it has both exocrine and endocrine functions
Its superior boundary sits at rib 5/6, while the gall bladder is located at the 9th costal cartilage, at the right midclavicular plane
It is separated into 4 lobes: Large right lobe, smaller left lobe, anterior inferior quadrate lobe and posterior superior caudate lobe.
106
What structures enter and exit the liver and where do they run?
The porta hepatis is a doorway into the liver on its posterior side, and it contains the portal triad: hepatic artery proper, portal vein and common hepatic duct. It runs within the hepatoduodenal ligament. The artery is anterior left, the bile duct anterior right, and the portal vein is the most posterior structure. The common hepatic duct splits into right and left hepatic ducts, as well as the hepatic artery proper.
The artery and vein supply the liver while the bile duct drains from the liver.
Veins draining blood from the liver are not able to be seen, as they run within the liver and join directly with the IVC.
107
How is the liver covered with peritoneum? What ligaments are associated with the liver?
The liver (and gall bladder) developed within the ventral mesogastrium, and so they are completely covered with visceral peritoneum. The falciform ligament passes to the umbilicus, and contains the ligamentum teres. These ligaments divide the right from left lobe
The area of the liver directly adhered to the diaphragm is not covered with peritoneum, and so is named the bare area.
Towards the upper edges of the liver, the peritoneum folds back on itself to form the right and left triangular ligaments. The coronal ligament runs atop the superior surface of the liver.
The lesser omentum emerges around the posterior side of the liver, with the ligamentum venosum running beneath it, the remnant of an embryonic vein.
108
What are the spaces and segments of the liver? What does this have to do with liver transplants?
There are right and left suprahepatic spaces, and right and left subhepatic spaces. The right subhepatic space is also called the pouch of morrison. These spaces should not, technically, be visible unless there is some kind of ascites.
The liver is separated into 8 functionally distinct segments, each with its own supply. Therefore, if part of the liver is removed, the rest will continue to function. The veins meet at the right, left and central hepatic veins before draining into the IVC (except caudate lobe, which has direct drainage).
109
What is the neurovascular and lymph supply of the gall bladder and liver?
Liver:
- Blood supply is 25% hepatic artery proper, 75% portal vein.
- Drainage: from sinusoids (leaky areas for blood to be passed through) into left, right and central hepatic veins, and directly into IVC.
- Lymph: Nodes at porta hepatis into coeliac nodes at T12
- Nerves: Visceral supply from coeliac plexus. Parasymp= vagus nerve. Symp. = greater splachnic nerve, from T5-9. Pain referred to epigastric region (although sometimes right shoulder if phrenic nerve of diaphragm is irritated.
Gall Bladder: Supplied by cystic artery (from R hepatic). Drained from cystic vein to portal vein.
Nerves: coeliac plexus, pain to epigastric region
Lymph: cystic nodes to hepatic nodes to coeliac nodes.
110
What is the arrangement of the biliary tree and how do the arteries diverge to give supply to the liver/gall bladder?
Biliary tree: liver secretes bile into R/L hepatic ducts, which fuse into the common hepatic duct. When fused with the Cystic duct (from gall bladder) they become the bile duct, which then fuses with the pancreatic duct to open into the 2nd part of the duodenum (hepatopancreatic ampulla of vater)
Opens into duodenum via sphincter of oddi.
Aorta -> common hepatic artery -> hepatic artery proper -> L. / R. hepatic artery. Cystic artery comes from r branch.
111
What is the structure and function of the gall bladder?
Has a fundus (hangs below liver), body and neck. Covered in visceral peritoneum.
Stores and concentrates bile- release is activated after presence of fat in the duodenum (by CCK release). Smooth muscle at the ampulla relaxes, and bile is released to emulsify fat.
112
What are gallstones?
They are crystals made of bile components, ranging from sand grain to golf ball size. If made of cholesterol, they will be yellow/white, although if made of bilrubin (a component of damaged red blood cells supposed to be broken down) they will be dark.
Choledocolithalsis refers to the presence of gallstones in the bile duct.
113
How can the portal system lead to venous disease?
If the liver scars (eg. cirrhosis), it provides less space for vessels and fewer routes. Therefore, there is a backlog, which increases pressure and foces blood back into the tissues that drain to it.
1. Oesophagus: causes dilation of submucosal veins in the lower 1/3, potentially causing bleeding (v. serious as this can cause clots in the stomach etc). Called oesophageal varices
2. Can reopen the ligamentum venosus, resulting in backflow to the veins of the abdominal wall, (called caput medusae)
3. Rectum/anus: causes dilation of superior and then inf. mid. rectal veins, causing anorectal varices. If the varices don't reach the epithelial part of the anal canal, they may bleed but without pain (due to no cutaneous pain sensors).
114
What are the key cells of the pancreas? How are their secretions released into the small intestine?
Endocrine- islets of langerhans, which stain pale and secrete hormones.
Exocrine- pancreatic acini, which stain darkly due to zymongen granules.
They produce preenzymes, fluids and elecrolytes
The ductal cells release HCO3-
Acinar cells have spherical nuclei located basally, mitochondria and zymogen granules. The proteins are synthesised in the rER, packaged in golgi, and accumulate as zymogen granules.
Acini -> intercalated ducts -> intralobular ducts -> interlobular ducts -> pancreatic duct -> hepatopacreatic ampulla of vater -> duodenum.
115
How is the pancreas stimulated?
By the vagus nerve
Presence of amino and fatty acids in the small intestint --> enteroendocrine cells make CCK --> stimulate acini cells
Acidic chyme --> increased secretin --> duct cells release HCO3-
116
How is the liver organised?
Hepatocytes are arranged in hexagonal columns. At each edge, there is a portal area, containing a branch of the hepatic portal vein, hepatic artery, and a bile duct. Between columns run the blood vessels which are a mix of arterial and nutrient rich blood. These drain into the central veins in the middle of each column. Between the cells run bile canaliculi. These emerge into bile ducts in the portal triad.
Hexagons are separatd by a fibrous interlobular septum.
117
What are the three ways of dividing bus the hexagonal liver columns?
Can form hepatic lobules- the hexagonal structures. These are an anatomical division, not functional.
Can form portal lobules- a triangular area between adjacent central veins, towards the centre of which bile flows
Can form functional divisions called liver acini. These run between 2 adjacent central veins as well as the two portal areas between them.
118
What are the different zones of hepatic acini, and what significance does this have?
The zones are based on where receives the most nutrients and oxygen between the two central veins. The portal triad runs on the boundary between lobules, and so nutrients and oxygen diffuse out. Zone 1 gets the most, zone 2 middle, and zone 3 least. This has implications for their:
- Enzyme profiles
- Functions
- Sensitivity to disease
119
How are hepatocytes organised relative to the sinusoids? What impact does this have on the bile ducts?
Hepatocytes have a high cell renewal rate due to the importance of their functions, and the organelles present depend on the zone they are found in. The cells are found either side of a sinusoid, the lining of which is made of endothelium and reticular fibres. Within the lumen of the sinusoid sit the kupffer cells, which keep the sinusoids clear. Between the endothelium and the microvilli of the hepatocytes is the space of disse, which contains fat-storing stellate cells. These are normally quiescent, but when activated they lead to fibrosis and obstruction of liver function.
Bile canaliculi run either side of the hepatocytes, before running into ductules, the ducts.
120
What are the adaptations the hepatocytes have for increasing transport rate?
Kupffer cells prevent obstruction and bacterial invasion
The villi of the hepatocytes increase the surface area
The endothelium are fenustrated and very thin, with only fine reticular fibres for support.
The sinusoids are very large, accomodating more than one blood cell at a time.
121
What is the liver's repertoire of responses to injury?
- Degeneration and intracellular accumulation (fat in cells, accumulation of bilirubin (bile salts)
- Necrosis/apoptosis
- Inflammation (esp. due to viral infections)
- Regeneration and scarring
- Fibrosis- loss of function, cirrhosis.
122
What is hepatic failure and how does it present?
Sudden and massive destruction, or gradual endpoint of chronic damage. It can be an acute episode.
Symptoms manifest only with 80-90% loss of function.
Decompensation can causes it when associated with increased demand- makes a tipping point.
Associated with high mortality.
Clinical features are jaundice, hypoalbuminaemia, and elevated ammonia, due to decreased ability to break it down. This leads to neurological dysfunction.
123
What is cirrhosis?
The destruction of hepatocytes and subsequent formation of fibrotic scar tissue. Results in chronic inflammation and very distorted lobules, and so decreased liver function.
The portal tracts are linked by fibrous septae, and nodules of proliferating hepatocytes surrounded by scar tissue form.
It disrupts the entire architecture- often laden blood bypasses the functional cells.
124
What is portal hypertension and what can it cause/be caused by?
Portal hypertension is increased resistance to portal blood flow. It can be prehepatic (a clot in the portal vein), posthepatic (RHS heart failure) or intrahepatic (cirrhosis- most common)
It causes ascites, as osmotic pressure in the liver goes up
Also shunting into spleen, oesophagus, umbilical region, rctum
Hepatic encephalopathy
125
What are the different viral hepatitis conditions?
Hep A- self- limited. Incubation 2-6 weeks, not chronic. Transmitted person to person. Asymptomatic or febrile + jaundice
Heb B- serious problem- acute hepatitis, but may become chronic and cirrhotic. Can lead to massive necrosis. Transmited by bodily fluids, and result from the immune response to viral antigens. Cirrhosis also increases the chance of cancer development.
Hep C- Major cause of liver disease, transmitted via bodily fluids. Causes acute inflammation, usually undetected, but chronic in majority.
126
What are autoimmune hepatitis and drug/toxin induced injury?
AI hepatitis- progressive hepatitis causes progressive chronic hepatitis due to antibodies.
DTILI- Hepatotoxins can be predictable or unpredictable. Predictable act dose-dependently and occur in most individuals.
Cause cholestasis, necrosis, fatty liver disease, fibrosis, granulomas, lesions in vessels and neoplasms.
127
What is alcoholic and non alcoholic fatty liver disease?
Alcoholic- big problem. Changes liver's lipid metabolism, decreases export of lipoproteins, increased free radicals and cytokines.
- Hepatic steatosis (fatty change)
- Alcoholic hepatitis
- Cirrhosis
Non-Alcoholic- assoc. with metabolic syndrome. Initially steatosis only, but may also develop inflammation and necrosis.
128
What is the relationship between normal, steatotic, hepatitis and cirrhotic livers in terms of alcohol?
Exposure -> steatosis. Steatosis -abstinence-> normal
Steatosis -> continued exposure -> cirrhotic
Normal -> severe exposure -> hepatitis. Hepatitis --> abstinence --> normal.
Hepatitis --> repeated attacks --> cirrhosis.
Abstinence and severe alcohol exposure also change hepatitis and steatosis.
129
What are the different enzyme patterns in the liver?
ALT and AST are enzymes responsible for the functioning of the liver lobule as a whole. Their levels are raised when there is inflammation or infection of the liver lobules.
GGT and ALP are enzymes released when there is a liver condition blocking the portal area- their levels are raised when this occurs.
130
What is the pathway of bilirubin metabolism and what can go wrong?
Bilirubin is released as a product of haem degradation. It is found mainly attached to albumin as it is not soluble in water by itself.
The liver takes up bilirubin and conjugates it by sticking it to a sugar, making it soluble in water. Most is then sent to the bile duct, where it is ejected into the small intestine (a small amount remains in the blood). In the small intestine it is converted into urobiligen, which is re-taken up into the blood and passed through urine along with the bilirubin-glucose that was present in the blood.
When there is increased haemolysis, the amount of bilirubin sent to the small intetine increased, increasing the amount of urobilinogen excreted. (and a small increase in blood bilirubin)
However, when there is hepatitis or cancer blocking the exit from the liver, the bilirubin backs up through the bile ducts and into the blood, where bilirubin-glucose levels increase.
131
What can cause jaundice?
- Increased haemolysis- a little
- Slowness of conjugation (gilbert's syndrome)
- Cholestasis- delay in moving bilirubin through the biliary system
- Obstruction- less movement through bile ducts
- Liver inflammation- liver has increased pressure, decreases bilirubin flow
132
What are the main liver enzymes, and what do they do?
- Alkaline Phosphatase (ALP): Transfers phosphate growth- comes from the liver (mainly from the biliary system during obstruction) as well as bone, when remodelling/growing. At puberty, levels can be 3-4x higher than usual. Virtually all liver disease shows increased ALP, but especially in obstructive liver disease.
- Gamma-Glutamyl Transferase (GGT): Comes from the biliary apparatus, with the largest source being the liver. It is caused by inflammation/obstruction of biliary system. Unlike ALP it can also be induced by alcohol and some drugs- most heavy drinkers have high resting levels, though it's not 100%. It takes 6+ weeks to return to normal
- Alanine Aminotransferase (ALT): Helps with recycling amino acids (intracellular). Main source from the hepatocytes. Has a long half life.
- Aspartate Transaminase (AST) Helps with amino acid recycling (intracellular). Main source is hepatocytes, but is less liver-specific than ALT. Has a short half life.
These two are elevated in most liver diseases, but especially so in hepatitis.
133
What is albumin and what can it tell us about the liver?
It is a compound synthesised by the liver. When rates fall, it means either decreased synthesis (liver issue), increased loss (kidney issue), non-specific illness or redistribution. It also has a long half life, of up to three weeks, so it can take a while to show any change after liver dysfunction occurs.
134
What can globulin, INR and glucose tell us about liver function?
Globulins reflect inflammation level: increase with disease
INR reflects synthesis of clotting factor. When it rises this shows the liver is failing
Glucose maintenance is the main responsibility of the liver: when levels fall, this is very bad.
135
What are the main signs of scarring and loss of liver function?
- Elevated GGT, ALP elevation
- Increased ratio of AST/ALT
- Increased globulins, INR
- Decreased albumin
- Increased bilirubin
- Increased NH3
136
What is a CEA test and what does it show?
It measures the levels of carcinoembryonic antigen in the blood, showing the level- higher levels increase likelihood of malignant cancer
137
What are the features of gilbert's syndrome?
- Variant in bilirubin conjugation, often presenting with other liver tests normal
- Increase in unconjugated billirubin, fasting or illness can worsen it.
138
What are the two classes of vitamins, how do they differ, and what are their digestion mechanisms?
Water soluble vitamins: Partially igested by mucosal hydrolyses, and absorbed into mucosal cell (modified) and sent to liver to be stored. No carriers necessary, circulate freely. Kidneys detect and remove excessive vitamins, and there is the potential for toxicity when taking supplements. They are needed frequently over days, and have short half lives.
Fat soluble vitamins: Undergo the same processes as fats- transported in by micelles, and exported into the lymph & plasma as chylomicrons. They need protein carriers, and are stored in cells associated with fat. They remain in these sites with an increased chance of toxicity when supplemented. They have long half lives, and tend to be needed over weeks/months.
139
What factors affect the bioavailability of vitamins?
- Efficiency of digestion and transit time
- Previous nutritional intake and status
- Other foods consumed simultaneously
- Food preparation method (eg. water soluble vitamins are easily hydrolysed when boiled)
- Source of the nutrient.
140
What is folate, what does it do, where does it come from and what can happen if it's deficient?
- A polyglutamate (although synthetic form is monoglutamate). It is water soluble
- It is a coenzyme involved in DNA synthesis, and also has a function in metabolism. It comes from leafy green vegetables, legumes, seeds, liver and fortified cereals.
When deficient, it causes megaloplastic anaemia- large, misshapen RBCs due to decreased methylation. It can also cause neural tube defects as the brain and spinal cord do not get properly covered. Increased risk of cancer, heart disease and mental issues and decreased hormone production.
Deficiency is caused by decreased intake, taking drugs, antagonistic action from other cells, alcoholism and pregnancy.
141
What is thyamine, what does it do, where does it come from and what can happen if it's deficient?
Thiamine is water soluble. It's a coenzyme of carbohydrate metabolism- it's needed to absorb other fooods. It also has a role in redox reactions- esp. ATP production in converting pyruvate to CoA. It comes from whole grains, pork, legumes. When it's deficient, it can cause wet beri beri (heart less able to beat, oedema due to haemostasis), dry beri beri (muscle wasting and inability to contract, eye issues), and wernicke's encephalopathy. Wernicke's encepalopathy is language and walking issues, unusual eye movements. If not prescribed thyamine, can develop korsakoff syndrome- amnesia, babbling, decreased cognitive function.
142
What is Vitamin A, what does it do, where does it come from and what can happen if it's deficient?
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Vitamine A (& beta-carotene) are fat soluble vitamins. VA is converted to retinol (repro), retinal (vision) and retinoic acid (growth). Beta carotene is converted straight to retinal. They are important for vision at nigh and colour, and for cell differentiation and mucous membrane formation (immune system).
They come from dairy and eggs, as well as dark vegetables and deep orange produce.
Deficiency causes night blindness, karatinisation (chicken skin).
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143
What is Vitamin D, what does it do, where does it come from and what can happen if it's deficient?
A fat soluble vitamin that comes from sunlight, liver and fatty fish. It is hydroxylated in the liver and then the kidney to activate it, so issues with these organs can risk vit D deficiency. It increases the absorption of, maintenance of calcium. In children it causes rickets (bending of long bones when weight bearing) and in adults it causes osteomalacia.
144
Who benefits from supplements of vitamins?
Those with poor nutrient intake
Those with increased nutrient and metabolic requirements
Those with maldigestion/absorption
Due to interactions between drugs/treatments and nutrients
Needs for pharmacological doses.
145
What is HCV and how is it treated?
Hepatitis C virus: causes chronic viral hepatitis. Transmitted via blood. Single stranded RNA virus with different genotypes. Majority of people unable to eliminate it- only manage it. Risk factors are injecting drug use, unscreened blood products/medical procedure, sexual and vertical transmission, occupational hazards and unsterile tattoos.
Was treated with interferon- causes flu like symptoms, but has been modified to prolong half life with PEG molecule addition. Only 50-80% cure, and long duration of symptoms. Now antiviral tablets.
146
What is hepatic encepalopathy, and how is it treated?
Result of chronic liver failure- early is mood/personality/sleep change and later is confusion, drowsiness and coma.
Liver unable to detoxify blood, blood shunted from portal circulation to right heart due to portal hypertension, causing it to bypass the liver.
Ammonia passes blood brain barrier
Treated with lactulose- decreases ammonia generation, converts ammonia to non-soluble form and increases bowel transit time. Variable treatment.
147
What is Budd-Chiari syndrome?
- Thrombosis of hepatic veins causing portal hypertension and hepatocellular damage. Presents with acute rapid abdominal pain, jaundice, hepatomegaly and ascites. Caused by many cases- external compression, post-partum, contraceptive pill, thrombophilia, increased RBC count.
Treated by shunting the blood into non-affected veins, prescribing anticoagulation factors or giving diuretics.
148
What are the main functions of iron?
Iron acts as a co-factor in the production of many proteins.
It joins with proteins to form heme, a crucial part of haemoglobin. Oxygen combines with the iron group when in the lungs, and releases it into the tissues. A similar principle is applicable in myoglobin for the muscles.
Cytochromes cause transfer of electrons and energy storage via iron redox (2+ vs 3+)
It's important for brain development, myelination differentiation and growth of neurons, and neurotransmitter regulation
149
How is iron transported around the body?
It is always attached to a protein. Transferrin is located in the plasma, responsible for carrying iron from site of absorption to site of storage. Transferrin is taken up by the cell where it releases its iron- therefore cells with high iron requirements (eg. haemopoietic cells) have high numbers of transferrin receptors.
In cells where iron is not required, it forms ferritin and is stored (unless excess iron is present, when it is excreted)
150
What are the two different varieties of iron, and how are each absorbed/used
- Haem iron comes from haemoglobin and myoglobin, from animal sources. It is absorbed directly into mucosal cells as the haem complex, where it is oxidised to form Fe2+ and is either converted to ferritin or let into the blood. Although only 10% of our dietary iron comes from haem form, 25% is absorbed.
- Non haem iron comes from vegetables and fortified foods, and is first first ionised by gastric juice as the pH of the chyme is raised. At the cell membrane, it is converted to Fe2+, bound to a receptor protein, and transferred into the cell. Although it makes up 90% of our iron consumption, only 17% of it is absorbed.
Haem iron from our own red blood cell breakdown is transported directly to cells that need it without first needing to be absorbed.
151
How is iron cycled within the body?
- Red blood cells are formed mainly in the bone marrow, where heme is synthesised from glycine and iron, and combined with globin. As RBCs have a lifespan of about 120 days, so the iron is released from the compound, taken up by transferrin and returned to the bone marrow. Its bioavailability is impacted by diet factors and physiological factors: transfer into the body is affected by body iron store size and the quantity of iron received.
152
What are some dietary factors that restrict/promote iron absorptions?
Enhanced by: Ascorbic, citric, lactic, hydrochloric acids.
- Meat & Fish Protein
- Sugar
- Vitamin C (most potent enhancer of non-H)
Inhibited by: Phytates
- Iron binding polyphenols
- Dietary fibre
- Tannins (tea)
- Calcium
- Phosphorous
- Oxalates (like spinnach)
153
What are the 3 classes of iron deficiency?
Stage 1: Depletion of iron stores; low serum ferritin levels (storage protein)
Stage 2: Deficient: low serum iron, high serum iron-binding capacity, reduced transferrin saturation and high unbound erythrocyte components
Stage 3: Iron deficiency anaemia: Low haemoglobin, hypochromic cells, microcytic anaemia, reduced mean cell volume.
154
What are the different portions of the pancreas and what structures are ant and post?
Head- lies in concavity of duodenum (with uncinate process wrapping behind SM vessels
Neck- narrow area, ant. to SM vessels
Body- passes lat, sup, post.
Tail- passes into leinorenal ligament, contacts hilum of spleen
Structures anterior to pancreas: Trans colon, stomach
Posterior: Bile duct, portal, splenic veins, IVC, aorta, SMA, psoas, supra renal gland, kidney, spleen
155
What are the ducts of the pancreas and where do they enter the duodenum?
Main duct runs from the tail of the pancreas into the ampulla of vater, through the sphincter of Oddi, with the major duodenal papilla at the entrance to the duodenum
There can also be an accessory duct which drains into the upper head and then the duodenum
So: Bile duct joins with pancreatic duct to form hepatopancreatic ampulla (of vater), passing through the sphincter of oddi and out the major duodenal papilla, into the descending duodenum
156
What is the arterial supply of the pancreas?
Coeliac trunk- gastroduodenal artery goes to superior pancreaticoduodenal
Also splenic artery gives off dorsal pancreatic and greater pancreatic.
SMA leads into the inferior pancreaticoduodenal
157
What is the venous, lymph and nerve supply of the pancreas?
Drained by portal vein or through the splenic/SMV into the liver and then into theICV
Lymphatic has two supplies- coeliac at T12 (main) or SM at L1 (minor)
ANS- Coeliac plexus, using greater and lesser splachnic (sympathetic) or vagus nerve (parasympathetic)
Pain referred to epigastric region
158
What is the spleen and where is it located?
Spleen is a single mass of lymph tissue, responsible for filtering and recycling blood
It lies deep to ribs 9-11 in the left hypochondrium.
It is attached via gastrosplenic and splenorenal ligaments
It is posterior to the tail of the pancreas, the left colic flexure and the stomach,and anterior to the left kidney and ribs 9-11
159
What is the gross anatomy of the spleen?
It has a diaphragmatic and a visceral surface, with an upper and lower pole. It is divided into 3 areas: Gastric, renal and colic.
It is connected to the stomach via the gastrosplenic ligament, and to the kidney with the splenorenal ligament.
160
What is the blood supply of the spleen? Where do the vessels travel?
Receives blood from:
Splenic vessels: travel within the splenorenalligament
Short gastric and gastroepiploic vessels- travel within the gastrosplenic ligament
Drains into portal vein, with coeliac (T12) nerves and lymph, greater splanchnic symp and vagus parasymp. Pain referred to epigastric region
161
What structures lie within the trans-pyloric plane?
```
The first part of the duodenum and pyloric region of the stomach
Hila of the kidneys
Neck of the pancreas
SMA
Portal vein
Fundus of gallbladder
```
162
What does the pancreas do and why is it more difficult to isolate?
Exocrine function: acini containing zymogen granules of trypsin, chymotrypsin, amylase, lipase, nuclease, elastase
Endocrine function containing islets of langerhans which secrete insulin, glucagon and other hormones
It's hard to diagnose as it's a hidden organ, very difficult to palpate
163
What are the three patterns of pancreatic pathology?
Congenital/genetic
Inflammatory
Malignant
164
What can cause pancreatitis (acute) and how does it present?
Pancreatitis can be classed as four main categories:
Metabolic- caused by alcohol
Mechanical- caused by gallstones or trauma
Vascular, caused by shock or vasculitis
Infection, caused by mumps
The symptoms are caused by the release of enzymes causing autodigestion of the pancreas.
- Proteases break down the protein structures and denature the acini, ducts and islets
- Lipases cause fat necrosis
- Elastases cause vessel destruction and haemorrhage
All this causes inflammation, oedema, impaired blood flow and ischaemia.
So basically 2 categories: Duct obstruction due to gallstones/ductal concretions (alcohol)- accumulation of pressureand enzymes
OR- primary cell injury due to viruses, drugs, trauma, ischaemia.
Presents as- epigastric pain, nausea, fever, tachycardia, tenderness.
165
How is pancreatitis (acute) diagnosed and managed? what are some possible complications?
- Diagnosed as high white cell count, elevated serum amylase levels, and a CT scan to conferm oedema, necrosis and pseudocysts. Managed by resting the pancreas with fluids, monitoring, nil by mouth etc
- Complications include hypotension, shock, renal and resp failure due to cytokine release. Low calcium, hyperglycaemia and jaundice, as well as pseudocysts
166
What causes chronic pancreatitis and how does it present?
Defined as repeated bouts of pancreatic inflammation, with loss of pancreatic parenchyma and a replacement by fibrous tissue.
Can be caused by heavy alcohol intake causing plugs, previous pancreatitis, severe malnutrition or be hereditary
Presents as fibrotic organ, atrophy of exocrine function, mild chronic inflammatory infiltrate and plugs. Symptoms are repeated abdominal pain (worsened by alcohol), malabsorption, pseudocysts and sometimes diabetes
167
How is chronic pancreatitis diagnosed?
Diagnosed by serum amylase (although not reliable) and CT imaging
168
What is pancreatic carcinoma and what does it cause?
Cancer of the pancreas, with very poor prognosis. Risks include smoking, hereditary factors.
Mostly adenocarcinomas, in head of pancreas (cause biliary obstruction), body and tail (remain silent, but spread everywhere and disseminate)
Presents as obstructive jaundice, weight loss, pain, pancreatitis, superficial clots and inflammation (thrombophlebitis).
Diagnosis is made via imaging
169
What are endocrine pancreatic tumours?
Very rare type of tumor in the islets of langernans- these may cause increased secretion of the pancreatic hormones
170
What is cholelithiasis and what can cause it? How does it present?
Presence of gallstones- Most are cholesterol stones, but some are bilirubin (pigment) stones.
Caused by bile becoming supersaturated and forming crystals
Cholesterol stones
Incidence greater in women and age, family history, undeveloped society and gallbladder stasis
Pigment stones
- Chronic haemolytic sydromes, or infection of the biliary tree
Can cause cholecystitis, biliary colic or cholangitis, obstrictuve cholestasis and pancreatitis
171
What is acute cholecystitis and how does it present/get managed?
Obstruction of neck of gallbladder or cystic duct- most commonly due to gallstones. Causes chemical irritation and bacterial infection
Presents as RUQ pain and tenderness, fever, increased neutrophils, bilirubin, alp and ggt.
Chronic results from long term low grade inflammation- causes thickened, contracted wall
Managed with conservative therapy (acute stage) or cholecystectomy (laporoscopic)
172
What is choledocholithiasis?
Presence of stones in biliary tree- causes obstruction (pain, jaundice), pancreatitis and cholangitis.
173
How does the duodenum detect and respond to different sensations?
It has vagal afferents which respond to luminal contents. These then stimulate the brainstem, and efferents return to the pancreas to stimulate it.
It also contains I cells, which sense the duodenal content and secrete CCK through their basolateral surfaces- these cells have a close assoc. with vagal afferents
S cells sense duodenal pH at their apical surfaces, and release secretin from their basolateral surfaces.
Enterochromaffin (serotonin) cells also stimulate gut motility and induce vomiting
174
What are the exocrine secretions of the pancreas?
- Alkaline (HCO3-) rich secretions which neutralize stomach acid
- Secretin, released in response to acid in the duodenum. This causes an increase in cAMP and in the CFTR transporters
175
How do the CFTR transporters aid pancreatic function and what can happen if they don't work properly?
CFTR transports Cl- out of the cell, as well as regulating the exchanger of Cl- and HCO3-. This helps to continue alkaline secretion from the pancreas.
Without this gene, Cl- gets trapped in the cell and pulls in Na+ and H2O, making mucus secretion thicker and potentially blocking the pancreatic ducts.
176
What are the pancreatic enzymes released from the pancreas and how do they get released/activated?
- Acinar cells make the pre-enzymes and store them in zymogen granules. When CCK is released (due to FA/AA/Vagus nerve), it stimulates the acinar cells via the vagus nerve or by directly impacting the acinar cells.
The pre-enzymes, trypsinogen, chymotrypsinogen and proelastase, are secreted and then activated in the duodenal lumen:
- Enterokinase on the brush borders converts trypsinogen into trypsin, which is then able to convert more trypsinogen and other proenzymes to their active forms
177
How is pancreatic secretion inhibited?
- Chemicals (glucagon, somatostatin, pancreatic polypeptide)
- Pancreatic polypeptide also acts on the brainstem to inhibit the vagal efferents.
- Peptide YY is released from the ileum and colon in response to increased FAA
178
How is the flow of bile controlled?
Bile acids promote bile flow into the canaliculi, and bilirubin is carried along with it. The high osmolarity of bile also pulls water into the bile, and the pressure causes unidirectional flow. As the bile ducts become larger the osmolarity decreases and water and Na are removed. Cholesterol and phospholipids are also actively secreted.
179
What is pancreatic division?
Where the pancreatic duct doesn't fuse with the bile duct, and instead drains into the duodenum through the minor duodenal papilla.
180
What is the enterohepatic ciruculation?
It is the circulation of bile salts- most (95%) are recycled as they are reabsorbed within the ileum and fed back into the portal vein. 5% are excreted, but they are replaced with cholesterol.
181
What are the examination features of prolonged biliary obstruction?
- Yellow sclera
- Skin scratch marks (bile salts under skin)
- Echhymoses (bruising)
- Palpable gallbladder (courvoisier's sign- always cancerous)
- Pancreatic mass
- Virchow's node
- Pale stool
182
What are polyps, and what are the categories they can fall under?
Polyps are circumscribed growths or tumors which project above the surrounding mucosa. There are two types:
Non-neoplastic
Neoplastic
Biopsy is necessary to be able to tell the two apart
183
What are the features of non-neoplastic polyps?
These are formed as a result of abnormal mucosal maturation, inflammation, or or architecture (hyperplastic).
Hyperplastic polyps tend to be common in the older person, and are usually sessile (no obvious stalk). These are elongated glands with folds creating a sawtoothed appearance.
Juvenile polyps are most common in children, and are usually present with rectal bleeding. They contain inflamed lamina propria, with cystically dilated glands. They are hamartomas (disorganised growths) but are not neoplastic
184
What are the features of neoplastic polyps?
Adenomas- these are more common in over-fifties. They can be single lesions or part of a polyposis syndrome. They can be sessile or pedunculated (with a stalk), and can be single or multiple.
They can be- tubular- most common, found in tubular glands
- Villous- projections of large sessile polyps (high malignant predisposition)
- Tubulovillous- mixed.
Dysplasia of the polyps is a range, and is characterised by enlarged, elongated hyperchromatic nuclei, with decreased cytoplasm and increased mitotic activity
185
What are the factors which dictate malignancy risk?
- Polyp size- most important factor. Large polyps can also cause bowel obstruction
- Architecture- villous more premalignant
- Severity of dysplasia.
186
What is the overall sequence from adenoma to carcinoma?
Normal epithelium --> hyperproliferative epithelium --> early adenoma --> intermediate adenoma --> Late adenoma --> carcinoma
187
What is the proof of the adenoma-carcinoma sequence?
- Popl'n with increased adenomas have increased carcinomas
- Distribution of adenomas and carcinomas in the LI is similar
- invasive carcinomas often show surrounding adenomas
- Risk of developing cancer is related to no of adenomas
- Peak incidence of adenomas antedates the peak of colorectal cancer by some years.
188
What can impact the development of colorectal carcinoma?
Diet high in red meat, carbs and low in fibre
| Aspirin and NSAID drugs can lower chance
189
What is the pathology of colorectal cancer, and what is its prognosis?
```
- Can occur anywhere in the colon- those proximal tend to grow through the wall of the bowel, while those distal tend to encircle it. Those in the RHS can present with iron deficiency anaemia due to small amounts of bleeding as the body struggles to maintain iron levels. This is too small to be noticeable in the stool (as those more distal do)
They come in 4 stages-
1. Only mucosa affected
2. Invade through to the muscle
3. Invade through the wall of the bowel
4. Spread into the lymph nodes.
Prognosis depends on cancer stage.
```
190
Why is nutrition in childhood so crucial?
Children's dietary patters last their lifetime, and they have a very different nutrition requirement compared with adults. Chronic malnutrition in childhood causes irreversible damage
191
What is the difference between child and adult nutrition requirements?
Children have increased demands due to their increased growth and development
Their organs also have a different functional capacity to adults'
Their metabolic activities are also related to their larger surface area- they dehydrate faster etc.
192
Why is breastmilk important and when should it be used?
It meets the full nutritional needs of the infant for the first six months of life- mostly fat, some carbs and very little protein.
It is always at the right temperature and osmolarity for baby's kidneys, and is easy to digest for developing pancreatic enzymes
Low risk of bacterial contamination, helps in gut maturation, development and immunity
Reduces risk of infectious diseases
193
When should solid food be introduced and what are the considerations with this?
Solids should be introduced around 6mos- small amounts of potential allergens should be introduced early, as the gut becomes more sensitive over time
Iron is very important to introduce
194
How is growth monitored? What is one of the main nutritional issues with NZ children?
Monitored using growth charts in centiles, and BMI charts the same way
Currently, 11% of children are obese, and a further 22% are overweight. This is correlated with poverty, increased consumption of poor food and increased sedentary behaviour
195
How do nutritional requirements change in adolescence and why?
Nutritional requirements are increased again due to pubertal growth, and calcium requirements are especially high as this is the time where peak bone mass is being accumulated.
196
What is the inflow and outflow of contents of the digestive tract?
```
IN:
2L in food
1.5L in saliva
2L in gastric secretion
1.5L in pancreatic secretion
.5L in biliary secretion
1L by small intestine (HCO3-)
Some K+ and HCO3- in LI
```
OUT
6.5L H20, Na+, Cl-, K+ reabsorbed by SI (large amount all at once)
1.9L H20, Cl-, Na+ reabsorbed by colon each day (small amount frequently)
.1L excreted in feces
197
How is glucose/amino acid absorbed by the intestine, and what cellular mechanisms and consequences are involved?
Na+/K+ exchangers on the basolateral membrane pump 3K+ into the cell and 2Na+ out, causing there to be a low resting conc. of Na+.
Na+/Glucose cotransporter (or Na+/amino acid) move Na+ into the cell down its concentration gradient and bring the nutrient along with it. The nutrient is then passed into the bloodstream using the facilitated diffusing channels
There are also Na+/2Cl-/K+ channels which increase cellular concentration of all three molecules. The Cl- is actively removed from the cell by CFTR channels and transferred into the lumen.
Water follows the osmotic gradient paracellularly. It can also move transcellularly, but at least one side of the membrane must have active transport channels.
198
What can go wrong with cellular digestive transport?
If the Na+/K+ transporter malfunctions, Na+ can build up within the cell and change its whole electrical and chemical gradient. If there is increased expression of the CFTR gene, more chloride channels will be formed and an increased amount of Cl- will be secreted into the gut lumen. Na+ will follow to keep the electrical balance, while H20 also follows to keep osmotic balance. This is alled secretory diarrhoea.
199
What is diarrhoea?
Excretion of:
- 200g/day+ faeces
.2L/day+ fecal H2O
3 liquid bowel movements/day+
If the origin is in the small intestine there will be a large volume, if in the large intestine it will be small.
Osmotic diarrhoea is due to malabsorption of macronutrients
Secretory diarrhoea is due to disease or tumour
200
How can cholera (secretory diarrhoea) be treated and why does this work?
Treated with oral rehydration therapy
This contains glucose, Na+, Cl- and HCO3-
HCO3- is present as diarrhoea can causes acidosis of the blood (due to HCO3- loss)
201
What controls Na+ movement and what is Na+ function?
Function is to maintain the osmolarity of the intestine, and it is controlled by the hormone aldosterone.
202
What is acute vs. chronic diarrhoea?
Acute- lasts up to 14 days, caused by infection (bacterial, viral, parasitic)
Chronic- lasts longer than 14 days, can be inflammatory, osmotic, secretory or fatty.
203
What are the different mechanisms of acute diarrhoea?
Different infectious agents can have different mechanisms
- Campylobacter causes inflammatory diarrhoea as it causes inflammation and exudate from the bowel
- Giardia causes osmotic diarrhoea is it causes villous atrophy and malabsorption of osmotically active nutrients
- Enterotoxigenic E. Coli causes secretory diarrhoea as the toxin stimulates increased fluid secretion
204
What is inflammatory diarrhoea?
It is diarrhoea due to inflammation of the bowel
- Inflammatory bowel disease, diverticulitis (inflammation of blocked diverticulae (pockets in colon)), SIBO, radiation /ischaemic colitis or colon cancer.
Inflammation in the colon increases the secretion of substances into the bowel.
205
What is osmotic diarrhoea?
Due to malabsorption of osmotically active nutrients
- Carb malabsorption can be due to lactose intolerance (primary or secondary- born vs. developed (temporarily) post infection), or irritable bowel syndrome
- Coeliac disease due to villous abnormality
- SIBO (malabsorption plus byproducts of bacteria)
- Laxative abuse as some contain unabsorbable solutes
206
What is secretory diarrhoea?
Due to irritation of the colon where increased secretion is initiated. Can be due to:
- Ileal resection causing bile acid malabsorption (irritates colon)
- Cholecysteectomy as bile flow is continuous into SI
- Microscopic collitis
- IBD, diverticulitis
- Neuroendocrine tumors that secrete gastrin/secretin etc.
- SIBO
- Disordered motility of the intestines- increases fluid/mucus
- Colon cancer
- Laxative abuse that raises colon motility
207
What is fatty diarrhoea?
Diarrhoea due to malabsorption of fat. Can be caused by:
- Pancreatic insufficiency
- Bile acid malabsorption (run out of recycled bile acid)
- SIBO
- Coeliac disease
- Short bowel disease
208
What is SIBO and how can it cause diarrhoea?
SIBO is small intestinal bacterial overgrowth. It occurs when the bacteria of the large intestine migrate into the small intestine, due to decreased gut motility (stasis, due to CT fibrosis, diabetes, excessive opiates), as well as adhesions or blind loops after surgery, strictures and small intestinal diverticulae. It can also be predisposed by some metabolic or immune disorders.
The bacteria de-conjugate the bile acids too early, so fat is malabsorbed. It also produces active by-products via its carbohydrate and protein degradation.
This causes pan-malabsorption, as well as inflammation of enterocytes. Additionally, the continued presence of food in the small intestine can cause secretory diarrhoea. Therefore, SIBO can cause all 4 forms of chronic diarrhoea
209
How can ulcers present in terms of diarrhoea?
Epigastric pain
| Black bowel motions (melaena) due to blooding in upper GI tract.
210
What is an ileostomy/colostomy and what can it cause?
- When part of ileum/colon is taken to abdominal wall, and the fluid produced drains into the bag. They are used when the bowel is actively inflamed after surgery, to give it time to settle before attaching it back to the rectum.
They have higher volumes of fecal output, which requres a higher sodium diet to prevent its loss due to colon bypass. The higher volume is due to the lack of colon to reabsorb the last liquid.
Complicated with a previous gastrectomy as there is no regulation of chyme outflow, so much higher volume is produced- treat with drugs reducing gut motility etc.
211
What are some possible consequences of short bowel syndrome?
- Reduced bile salt re-uptake (fatty diarrhoea due to decreased bile salt circulation)
- B12 deficiency
- Malabsorption of water and nutrients (osmotic diarrhoea and dehydration)
- Outlook improved if colon and ileocecal valve are left- colon absorbs water and ileocaecal valve brakes fluid transit
212
How can short bowel syndrome be adapted to or treated?
- Villi undergo hypertrophy to meet increased demand
- Colon increases its absorptive capacity
- Low salt diet to reduce secretion due to osmosis
- Anti motility drugs
- Acid suppressants to reduce fluid release
- Cholestyamine
- Total parenteral nutrition- feeding through IV supply
213
What are the classic features of functional gut disorders?
No structural or tissue abnormalities
Constellation of symptoms without pathology- disturbed motility, visceral hypersensitivity, grain-gut dysfunction, psychological factors
Therefore, they are diagnosed by looking at the constellations of symptoms, and by excluding other potential pathologies
214
What are the symptoms of IBS, and what can cause alarm in terms of these?
- Swinging bowel habit- diarrhoea to constipation and back
- Abdominal pain, relieved with defecation
- Urgency and incomplete evacuation, passage of mucus, abdominal bloating and excessive flatus.
- Also fatigue, other GI symptoms, aches, pain during periods/sex, palpitations, poor sleep and urinary issues
- Alarm symptoms include age of patient, short history, nocturnal pain or diarrhoea, anaemia, weight loss, vomiting and family history of colon cancer
215
What is an overview of the pathophysiology of IBS?
- Altered gut motility- constipation or diarrhoea (or a mix)
| - Visceral hypersensitivity- increased detection of distension and lower pain threshold for this
216
What is the treatment for IBS?
- Manage symptoms- fibre supplements, laxatives/anti-motility drugs, antidepressants (pain)
- Dietary exclusions- removal of many sugars and fermentable foods
- Natural options (some evidence depending on patient belief)
- Lifestyle and psychological therapy
217
What is IBD, what are the two different components of inflammatory bowel disease, and what is involved with each of them?
IBD is the disruption of the integrity of the epithelial barrier, creating an abnormal immune and inflammatory response.
- Ulcerative colitis (disease beginning in the rectum and spreading throughout the colon, with mucosal inflammation and no macroscopic ulceration unless severe)
- Crohn's disease (formations of 'skip lesions' throughout the GI tract, starting small and progressing to deep, fissuring ulcers)
218
What factors can increase predisposition to IBD?
Genetics- first degree relatives, ethnic group etc. (although not common)
Environmental- common in western societies as we have less exposure and subsequent tolerance to infections
Smoking increases risk of crohns, but is protective in UC
219
What is Ulcerative colitis, and how does it present?
Inflammation of the mucosa of the colon only, which can progress to ulceration when severe. It shows crypt distortion and atrophy, as well as their being invaded by neutrophils. Also loss of goblet cells and formation of paneth cells where they are not normally found (secretes lysozyme, TNF-a etc.
Presents as diarrhoea with blood, frequent and urgent bowel motions, abdominal discomfort and fever/weight loss/malaise
Causes mild anaemia and raised ferritin (acute phase protein) , and iron deficiency with low ferritin if prolonged.
220
What is crohn's disease, and how does it present?
Crohn's disease is the formation of 'skip' lesions anywhere along the gut tube. They start out shallow and small, and progress to being deep, penetrative ulcers. They form fistulae with other parts of the gut.
They create transmural (across the whole wall) inflammation, and can form non-necrotising granulomas.
There are 4 sub-types
- Inflammatory- colitis, ileitis, gastritis or duodenitis (presents as pain, discomfort, diarhhoea etc.)
- Stricturing- results in pain, distension, vomiting and bowels not opening- initial stricture due to oedema, following due to fibrosis
- Fistulising- abnormal connection formed between gut and another structure- can be gut-gut, gut-skin, gut-colon, rectum and vagina etc.
- Perianal- causes abscesses, fistulae and fissures
Can result in anaemia and raised ferritin, iron deficiency with low ferritin if prolonged, and malabsorption causing Iron/B12 deficiency
Also can affect eyes, liver, bile ducts, joints and skin.
221
How is crohn's disease treated?
Treated using drugs- 5ASA, then sterioids, then immunosuppresants, then biologics (anti-TNF).
Surgery is considered when other options are exhausted: resect diseased bowel.
222
How do you differentiate between IBS and IBD?
IBS is common, IBD is not.
IBS is unlikely in older people, IBD occurs at any age
IBS causes alternating bowel, IBD causes diarrhoea
IBS causes no bleeding, IBD causes bleeding
IBS causes no alarm symtoms or abnormal bloods, whereas IBD does
IBD also is associated with other features- perianal disease, extra-intestinal diseases
223
What are some common liver/Gallbladder pathologies, how do they present and what imaging modalities should be used?
Liver: trauma, cancer, cirrhosis
Gallbladder: gallstones, cancer
Symptoms are pain, jaundice, abnormal liver function tests
Image using ultrasound first (unless trauma) then CT- MRI and ERCP can be used but not often
224
What are some common spleen pathologies, how do they present and what imaging modalities should be used?
- Trauma, cancer, portal hypertension, congenital issues. Most often use ultrasound and CT
225
What are some common gut pathologies, how do they present and what imaging modalities should be used?
- Free air anywhere in the abdominal sacs
- Stomach: cancer
- Small bowel: crohn's, cancer, ischaemia
- Colon: cancer, infection, appendicitis, IBD, ischaemia
Stomach: X ray, then barium/endoscopy, then CT (unless older patient- then CT first)
Small bowel: presents as pain, haematemesis and vomiting. Investigate with X ray then CT/US
Large bowel: presents as altered bowel habits, PR blood and malaena. Investigate with X ray, then colonoscopy, then barium enema and then a CT
226
What are the different criteria for coeliac disease stages?
```
0- normal
1- increased lymphocytes
2- increased crypts
3- flattened villi
4- atrophy of villi
```
227
What is coeliac disease and how does it present?
Causes villous atrophy and hypertrophy of crypts due to production of antibodies that attack the gut lining. These are all IgA antibodies: anti TTG, EMA and DGP.
Presents in childhood as failure to thrive, irritability, diarrhoea, poor appetite, Fe deficiency, shortness, and abdominal distension
Undiagnosed adults present with abdominal bloating and discomfort, iron deficiency and potential folate deficiency
228
What is the genetic link with coeliac disease?
There are two susceptibility genes call HLA DQ2 and 8.
229
How is coeliac disease treated?
It isn't treated, but managed- a gluten free diet alleviates the symptoms, free of wheat, rye and barley.
230
What are the drugs responsible for inhibiting gastric acid secretion?
Histamine stimulates secretion, so the inhibitors are modelled on this structure- they can bind, but cause no signal transduction.
- H2 receptor antagonists are competitive for the H2 receptors. They may not fully bind to all H2 receptors and stop all acid secretion, and they can be overcome by a strong agonist effect, but they are safe and good for first doses (strong effect which weakens after many doses). They are also absorbed regardless of food being present or not.
- Proton pump inhibitors are absorbed into the blood and then passed into the parietal cells, where they block the passage of H+ out of the cell into the lumen of the stomach. They have a short half life, but prolonged action, necessitating only one dose per day. They inhibit more than 90% of stomach acid. Problems are that they require food to activate the pumps (in order to take up the drug), and the level of acid suppression may cause bacterial overgrowth, unsterilized chyme, B12/Fe malabsorption and ECL hyperplasia due to high gastrin levels.
231
When would you use H2 antagonists vs. protein pump inhibitors?
H2 antagonists are good for first doses and rapid onset conditions, as well as nocturnal acid secretion.
Protein pump inhibitors are good for maintenance prescriptions as the effect doesn't diminish- ie. gastric ulcers and acid reflux
232
How does the digestive system affect the drugs prescribed to it?
- Secretion of acid in the stomach degrades drugs (although it can also increase drug absorption)
- Drugs can affect the rate of gastric emptying- need to match insulin and meals, as well as alcohol absorption
- Drugs can affect hepatic enzyme functionality
- They can also affect the enterohepatic circulation and biliary secretion
233
What are some solutions to getting drugs to the small vs. large bowel (through the stomach)?
- Use enteric coated proteins- these have an acid resistant coating, made of minimicrospheres in a gelatin framework.
- Can use non-enteric-coated drugs but give a proton pump inhibitor in addition
- For colon- can join molecules together using a diazo bond- this can only be broken apart by bacteria in the colon, and so is immune to gastric acid (although it can have adverse effects- also dose-dependent effects)
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What is the problem with NSAIDs and how can this be solved?
- NSAIDs inhibit COX1, which is responsible for prostaglandin production, as well as mucus, bicarbonate and new epithelium generation.
They also cause increased adhesion molecules, leading to more neutrophils and microvascular ischaemia. This results in erosions (mucosal breaks) and ulcers, with potential GI bleeding and perforation.
- Can use alternatives (analgesics)
- Can use lowest possible dose, and drugs with least risk of bleeding
- Can co-prescribe protective drug (ie proton pumph inhibitors, prostaglandins)
- Can also use NSAIDs with COX 2 inhibitors, which reduce the risk of bleeding- although these are expensive and increase the risk of myocardial infarction.
