Pathophysiology Exam Quiz - Endocrine, Small Bowel, Bariatric and HPB

Welcome to First Incision. the podcast about preparing for the General Surgery Fellowship exam. I'm your host, Amanda Nikolic. Let's get started with our team timeout. Our patient today is actually just pathology, which crosses all of the general surgical curriculum. This first episode, we're going to look at some endocrine small bowel. bariatric and hepatobiliary pathology because there was way too much to fit into one episode.

I've had a lot of feedback about the first episode I did like this and people have found it really useful for their preparation. It gives you an opportunity to see where your gaps are and what you need to work on and can be repeated. So you can try out questions again that maybe you found. more difficult. Special shout out to Sharon J in New Zealand and Alex from Instagram who both asked for a pathology episode. This is for you guys. Thanks so much for listening and for your feedback.

So we're going to start off in the endocrine module. And our first question is, what is the pathophysiology of a multinodular goiter? Multinodular goiter is the result of TSH stimulation of the thyroid in the setting of a risk factor, whether that's goitrogens, which can be substances such as... brassica vegetables or certain drugs that interfere with iodine uptake by the thyroid or in areas of iodine deficiency.

And this TSH stimulation in combination with the risk factors leads to diffuse enlargement of the thyroid, which becomes progressively more nodular due to hemorrhage and resultant scarring and involution of the gland, leading to the irregular. nodularity. The second question is, what is the pathophysiology of Graves Eye Disease?

The pathophysiology of Graves Eye Disease is... cross-reactivity of the anti-TSH antibodies with the tissues in the retroorbital space leading to mucopolysaccharide deposition in the retroorbital fat. causing proptosis, so pushing the eye out, and also causing the muscles to become hypertrophic. What is the pathophysiology of Hashimoto's thyroiditis?

Otis thyroiditis is an inflammatory condition of the thyroid associated with the presence of antithyroid antibodies. And this includes thyroid peroxidase antibodies and... antithyroglobulin antibodies. And this leads to infiltration of the gland with CD4 helper T cells, leading to often an initially hyperthyroid state and eventual destruction and fibrosis of the gland, leading to hypothyroid state.

So our next question is, what is the process of calcium homeostasis? And they asked me this in my pathophysiology viva exam. Calcium homeostasis is regulated by a complex endocrine pathway involving the parathyroid glands, the kidneys, the gastrointestinal tract and the bones. So in response to...

decreased calcium, the parathyroid glands secrete parathyroid hormone. And parathyroid hormone has a number of different effects that act to increase the levels of calcium in the bloodstream. So it first travels to the kidneys. and increases the activation of vitamin D from 1-alpha-hydroxy vitamin D to 125-alpha-hydroxy vitamin D. And this activated vitamin D... acts on the gastrointestinal tract to increase calcium and phosphorus absorption from the food.

The other action on the kidneys is that it increases calcium reabsorption from the tubules and also reduces phosphate excretion. It also acts on the bones by increasing osteoclastic activity to increase the release of calcium and phosphorus from the bones into the bloodstream. And all of these mechanisms act to increase the level of calcium in the bloodstream.

This then acts as a negative feedback mechanism back onto the parathyroid glands to reduce PTH secretion. A little bonus question about calcium. Pathophysiology of familial hypocalceric hypocalcemia. The pathophysiology of FHH is an autosomally dominantly inherited inactivating mutation in the gene that encodes the calcium sensing receptor.

And mutations in this gene lead to altered calcium sensing and therefore an inappropriate parathyroid hormone release with respect to the serum calcium concentration. What is the pathophysiology of Graves' disease? The pathophysiology of Graves' disease is that it's an autoimmune disease with the release of thyroid stimulating antibodies known as anti-TSH receptor antibodies. that bind to the TSH receptor and stimulate the thyroid to make excess thyroid hormone.

Sticking with endocrine but changing tact a little bit, what is the pathophysiology of aldosterone? The pathophysiology of aldosterone is that it's a mineralocorticoid secreted by the adrenal cortex. It causes sodium to be absorbed and therefore fluid retention and potassium to be excreted by the kidneys. So in primary... hyperaldosteronism or Kahn's syndrome, patients develop a high blood pressure and low potassium level.

Linked into this question, let's ask, what is the adrenal gland? What are the layers and what hormones does it make? The adrenal gland has two main components, the cortex and the medulla. The cortex has three layers, the zona glomerulosa, zona fasciculata and zona reticularis. The zona glomerulosa makes aldosterone. The zona fasciculata makes glucocorticoids. And the zona reticularis secretes sex hormones.

And the medulla contains the chromaffin cells, which are the cells that make noradrenaline. And there's an enzyme in the medulla. the PNMT enzyme that converts noradrenaline to adrenaline. So the extra adrenal paragangliomas only secrete noradrenaline, not adrenaline, because they don't have this enzyme. But tumors coming from the adrenal, so pheochromocytomas, do secrete adrenaline.

Okay, let's move on to a new topic. We're going to go to the small bowel curriculum. What is the pathophysiology of a small bowel obstruction? The pathophysiology of a small bowel obstruction is that early on, the contractions and intestinal motility increases, leading to a colicky abdominal pain, usually felt in the mid-abdomen as this is a mid-gut structure. Later on, the bowel wall fatigues and dilates with less frequent and less intense contractions.

As the bowel wall dilates, there's water and electrolytes that accumulate intraluminally, and this leads to third space losses, contributing to dehydration and electrolyte abnormalities. The vomiting and fluid losses also lead to loss of electrolytes, specifically potassium and chloride, and may lead to significant acid-base abnormalities. Because of the hypovolemia, patients develop renal impairment, may develop hypotension or shock due to the third space losses.

The increased intra-abdominal pressure leads to ventilation issues. And then there's decreased venous return due to the increased intra-abdominal pressure as well. Locally in the bowel wall, the increased intraluminal pressure leads to decreased mucosal blood flow, which eventually leads to venous obstruction, arterial... occlusion and progression to ischemia, perforation and peritonitis in some cases. And there's also increased rates of bacterial translocation.

What is the pathophysiology of small bowel interception? The pathophysiology of interception is that usually a lead point, such as a polyp or a tumour, Or in kids, an inflamed Peyer's patch leads to invagination or telescoping of the intestine into a distal segment. The bowel that has interscepted, called the interscept... can then become compressed and edematous. This can lead to venous congestion, leading to inflow obstruction and ischemia and gangrene of that segment of bowel.

What is the pathophysiology of the metabolic sequelae of a gastric outlet obstruction? So firstly, the metabolic sequelae of a gastric outlet obstruction is a hypochloremic, hypokalemic metabolic alkalosis with paradoxical aciduria. And so in gastric outlet obstruction, there's vomiting leading to loss of gastric hydrochloric acid, so chloride and acid, leading to dehydration and a metabolic alkalosis.

With progressive dehydration, the kidneys then have to preferentially keep sodium over potassium. So they keep the sodium and excrete the potassium, leading to hypokalemia. And then as this becomes worse and worse, the kidneys then start switching and keeping the sodium and getting rid of acid. So the urine becomes acidic even though the patient is alkalotic, leading to the entire clinical picture of a hypochloremic, hypokalemic.

Metabolic alkalosis with paradoxical aciduria. What is the pathophysiology of SMA syndrome or superior mesenteric artery syndrome? The pathophysiology of SMA syndrome is that usually the fat and lymphatic tissues around the SMA provide protection to the third part of the duodenum, which it passes over. But in conditions of rapid or severe weight loss, this cushion around the SMA is diminished.

causing an acute angulation of the SMA at its origin off the aorta and causing compression of the third part of the duodenum, leading to duodenal obstruction and also a gastric outlet obstruction type picture. with the metabolic sequelae we just talked about in the last question. What is the pathophysiology of chronic mesenteric ischemia?

The pathophysiology of chronic mesenteric ischemia is that this is a vascular disease caused by atherosclerosis of the vessels feeding the gastrointestinal tract, so the celiac axis, the SMA, and the IMA. These patients develop chronic abdominal pain and symptoms caused by a gradual decrease in blood flow to the intestines, with symptoms more prevalent after eating due to the increased blood flow required for digestion.

Because there is an abundant mesenteric blood supply and atherosclerosis often progresses slowly, patients may grow a number of collateral pathways and therefore may not develop symptoms until they have quite severe and advanced atherosclerotic disease. What is the pathophysiology of acute mesenteric ischemia? The pathophysiology of acute mesenteric ischemia is that no matter the cause, whether it's a thrombus, embolism, non-occlusive or venous thrombosis,

The patients develop mucosal ischemia first, leading to a visceral pain but no clinical signs. There's then progressive injury. causing epithelial separation at the basement membrane, leading to capillary damage and increased mucosal permeability. As the injury progresses, patients get progressive mucosal injury. with loss of the mucosal integrity, bacterial translocation, the development of pneumatosis intestinalis, and eventual gangrene and perforation.

If reperfusion is established, patients may also suffer from a reperfusion injury with accumulation of oxygen-free radicals leading to an inflammatory infiltration into the bowel.

and also the release of lactate and potassium-rich blood into the systemic circulation, which may lead to a systemic response. What is the pathophysiology of carcinoid syndrome? So carcinoid syndrome is caused by release of vasoactive amines and substances by well-differentiated neuroendocrine tumors of the digestive tract and sometimes the lungs. The products that are released include serotonin, histamine, tachykinins, calicrenin, and prostaglandins.

And these lead to the clinical syndrome of carcinoid syndrome with diarrhea, flushing, and the development of cardiac valvular lesions. For carcinoid syndrome to occur for neuroendocrine tumors of the gastrointestinal tract, there really needs to be established metastatic disease because if these...

vasoactive amines are being released by the tumor in the GI tract, then these substances pass through the liver first through the portal system and are inactivated by the liver. So the disease needs to be metastatic in the liver or elsewhere to be released into the systemic circulation to develop this syndrome. What is the pathophysiology of jejunal or ileal diverticulum?

So jejunal and ileal diverticulums are thought to be acquired pulsion diverticulums, often found on the mesenteric border of the small bowel. So they're a pulsion diverticulum of the mucosa and submucosa only, not the full layers of the muscle wall. And they're thought to be due to a motor dysfunction of the smooth muscle or of the myenteric plexus. And so this motor dysfunction leads to disordered contractions, increased intraluminal pressure, and resultant herniation of the mucosa.

What is the pathophysiology of blind loop syndrome or small bowel bacterial overgrowth? So there are a number of usual mechanisms that limit the bacterial overgrowth in the small bowel. So this includes continued flow of luminal contents from peristalsis, the acidity of the gastric. contents entering the small bowel, local immunoglobulins, and prevention of reflux of colonic contents by the ileocecal valve.

And so if any of these mechanisms are overcome, then you can get overgrowth of bacteria in the small bowel. There's a number of different... outcomes of this. So the first is that the bacteria deconjugate bile salts, leading to reabsorption of the deconjugated bile salts in the jejunum. And this means that fats are not absorbed well. The unabsorbed fatty acids also enter the colon, leading to diarrhea because of increased net secretion of water and electrolytes from osmosis.

Patients develop hypocalcemia because the calcium gets bound to these unabsorbed free fatty acids. And then because the calcium is getting bound to these fatty acids, they can't bind to oxalate and help with the excretion of oxalate from the colon. So oxalate gets reabsorbed into the body and then gets secreted in the kidneys, leading to... renal stones. Anaerobic bacteria in the small bowel also bind to B12, leading to malabsorption of B12 and macrocytic anemia.

And bacteria can also catabolize carbohydrates and protein, contributing to malabsorption and weight loss. Because of the lack of absorption of fatty acids and fat, patients also get issues absorbing fat-soluble vitamins, and so they get deficiency of vitamins A, D, E, and K. And there's other changes that lead to GI symptoms, including bloating, constipation, diarrhea, and pain because the...

Bacteria ferment unabsorbed carbohydrates, leading to hydrogen and methane gas, and therefore patients get these other side effects. What is the pathophysiology of celiac disease? So celiac disease is an autoimmune disease with an abnormal cellular or T cell mediated and humoral response to ingestion of glyden, which is a component of gluten. And this essentially leads to mucosal damage. And the mucosal damage can be seen as atrophy of the mucosal folds, leading to loss of brush border enzymes.

loss of the stimulus for pancreatic and bile secretion, protein loss due to exudation of proteins across an abnormal mucosa, and...

may in the long term lead to long-standing disease such as intestinal lymphoma if patients aren't on a diet that excludes Glyden. What is the pathology of small bowel adaptation? The pathology of small bowel adaptation is that it's a number of both structural and functional changes to the small bowel that increase the absorptive capacity of the small bowel. So the structural changes are that the small bowel lengthens and dilates, the muscle wall becomes thicker, and the villi increase in size.

Functional changes include a slowing of peristalsis to reduce transit time and increase absorption. It also leads to an increase or upregulation of the enzymes at the brush border to improve absorption of the small bowel. And the ileum is better at adapting than the jejunum. What is the pathophysiology of loss of the terminal ileum? So the main function of the terminal ileum over other parts of the bowel is its ability to absorb bile salts and also vitamin B12.

So reduced absorption of B12 leads to a macrocytic anemia. Absorption of bile salts in the terminal ileum leads to a reduction of the enterohepatic circulation of bile salts and therefore a decreased pool of bile salts to be excreted. So this interferes with bile salt excretion. therefore reducing the absorption of fat and also reduces the absorption of fat-soluble vitamins, vitamin A, D, E, and K. Obviously, vitamin D is important for bone health, vitamin K for clotting factors.

The consequences of non-absorbed bile salts entering the colon is watery diarrhea as they stimulate colonic fluid secretion. They can also get steatorrhea due to fat malabsorption. Because the fat is reaching the colon, then patients also develop renal stones. because the non-absorbed fatty acids bind to calcium, excreting calcium and leading to hypocalcemia, but that calcium would usually be bound to oxalate, which is then instead reabsorbed into the circulation and excreted in the...

kidneys and precipitates out as oxalate renal stones. What is the pathophysiology of radiation enteritis? They asked this in my written exam for the fellowship. So the pathophysiology of radiation enteritis is that this is a late effect and it's due... to a progressive obliterative arteritis, leading to submucosal fibrosis, vascular thrombosis and vascular insufficiency, which causes ischemia and fibrosis.

of the small bowel okay let's take a brief foray into bariatric surgery What is the pathophysiology of obesity? So obesity is a multifactorial process, probably contributed to by genetic predisposition, environmental factors, sociocultural factors, hormonal. metabolic, behavioral, and physiological factors. And it's very hard to tease out one single contributing cause of obesity because there really are multiple causes. Essentially,

Obesity leads to accumulation of adipose tissue, which is metabolically and hormonally active. And these adipose cells secrete adipocyte-derived peptides such as lectin and cytokines, which are all collectively referred to as adipokines. And these adipokines contribute to a state of chronic low-grade inflammation, which in turn interferes with many physiological cellular processes, such as insulin signaling.

And this leads to the metabolic derangements that we often see in obesity, such as type 2 diabetes. And so essentially patients have a pro-inflammatory state. metabolic dysfunction, and endothelial dysfunction, which all contribute to the pathophysiological sequelae of obesity. And what are the theorized pathophysiological mechanisms of why bariatric procedures actually result in weight loss.

There are a number of proposed mechanisms why bariatric procedures work. The first is that there is a physical restriction of the amount of food that patients can eat. due to small stomachs or pouches that are created by the surgery. The second is malabsorption. So some procedures such as a bypass procedure will... bypass some of the absorptive length of the bowel, leading to malabsorption of nutrients and calories.

The other proposed mechanisms is that there's decreased hunger signals for patients, leading to reduced food intake. There's also an increase in the number of cells that secrete postprandial satiety gut peptides such as GLP-1, GLP-2, and also vagal signaling is changed post-bariatric surgery, which may play a role in satiation. reduction of signaling of ghrelin, which is a hunger hormone, and reduction in meal sizes and altered food preferences.

Okay, let's move on to the hepatobiliary module. What is the pathophysiology of primary sclerosing cholangitis? So I always remembered this as the same as radiation enteritis. So it's a progressive obliterative fibrosis. And except in PSC, it's a progressive obliterative fibrosis of the intrahepatic and extrahepatic biliary tree, causing strictures, secondary...

cholangitis and progressive liver failure. What is the pathophysiology of chronic liver failure? And remember, this is pathophys, so not talking about causes, just the pathophysiology. The pathophysiology of chronic liver failure is that there's a gradual and incremental loss of liver cell mass and function due to chronic or repeated cell injury and attempts at repair.

There's a fibrosis and scarring process associated with this regeneration and repair that leads to the clinical condition of cirrhosis with a typically small, shrunken...

irregular liver, and an increased risk of the development of hepatocellular carcinoma. What is the pathophysiology of an amoebic liver abscess? So an amoebic liver abscess is an infection caused by Entamoeba histolytica, which is a parasite. And the pathophysiology is that there's fecal-oral spread and humans... ingest the cysts through oral ingestion, and then trophocytes are released and multiply in the colon, especially in the cecum, which can cause diarrhea, but only in about 30% of people.

And then these trophocytes reach the liver through portal venous and lymphatic circulation. or sometimes by direct extension through the colon wall into the peritoneum and then through the liver capsule, leading to an infection in the liver. And he knew that this question was going to be next after that one. What is the pathophysiology of high-dated liver cysts and the life cycle of the parasite involved in this infection?

So a high-doubted liver cyst is caused by an infection with Echinococcus granulosis, most commonly, and rarely the Echinococcus multilocularis parasite. The way that this happens is that the Echinococcus granulosis resides as an adult tapeworm in the small bowel of the definitive host, which is the dog. Humans are an accidental host and we ingest the eggs of the echinococcus granulosis through a fecal oral route. The eggs then release the larvae in the gastrointestinal tract.

due to an interaction with bile salts and trypsin. The larvae then penetrate into the wall of the jejunum. and are transported via the portal circulation to the liver or via the lymphatics to the lung, where these larvae develop into high-dadded cysts. And the cysts then enlarge asexually, producing protoscolyces, which are contained in the brood capsules, as well as daughter cysts that fill the cysts.

When the organ containing the cysts are ingested by the definitive host, the dog, then the protoscholaces evaginate and the scolaces of the organism attach to the intestine of the dog and develop into adult tapeworms. which complete the life cycle. Obviously, dogs aren't usually eating our livers, so the usual intermediate host is the sheep, which is why we are called accidental hosts. What is the pathophysiology of portal hypertension?

The pathophysiology of portal hypertension is essentially a combination of two things. Number one is an increase in the vascular resistance to portal flow. And number two is an increase in portal blood flow. The increase in vascular resistance is due to architectural distortion in the liver.

And also due to an imbalance between the endogenous vasoconstrictors, which is increased, and the vasodilator nitric oxide, which is decreased. And so this leads to vasoconstriction in the portal circulation. The second thing, the increase in portal blood flow, is due to splanchnic vasodilatation. And most of the medications for portal hypertension are aimed at reducing this increased splanchnic blood flow. What is the pathophysiology of ascites in chronic liver failure?

The pathophysiology of ascites is a combination of factors. There's an increase in portal venous pressure, causing splanchnic vasodilatation. which alters the capillary pressures and permeability, leading to fluid leakage into the peritoneal space. And there's also increased lymphatic pressure, leading to transudation and leakage of fluid from the lymphatic system. The low plasma protein due to reduced production of proteins in the liver leads to reduced osmotic pressure of the plasma.

leading to less fluid being removed from extra vascular sites and more fluid leaking from the blood vessels. There's also increased sodium and water retention in chronic. due to reduced circulating plasma volumes and pooling of blood in the splanchnic system. This leads to messaging to the kidneys to activate the...

juxtaglomerular apparatus and increase aldosterone secretion, leading to retention of sodium and water. What is the pathophysiology of cholangitis? The pathophysiology of cholangitis is that biliary obstruction causes cholestasis and increased pressure in the biliary system. This leads to infection and... cholangiovenous reflux causing translocation of bacteria from the biliary system into the venous system leading to systemic sepsis. What is the pathophysiology of gallstone formation?

So the classic triad of the formation of gallstones is hypometility of the gallbladder, supersaturation, and nucleation. So bile is usually made up of... bilirubin, bile salts, water, phospholipids, and cholesterol, hypomotility of the gallbladder, leads to stasis of bile, leading to absorption of water, and concentrated bile, leading to an increased propensity to the development of gallstones.

supersaturation of bile with cholesterol crystals due to obesity or hypercholesterolemia causes ability of the cholesterol to... precipitate out as cholesterol stones. And nucleation is the idea that nucleating factors such as mucin can predispose

for the precipitation of components of bile to form stones. What is the pathophysiology of acute pancreatitis? The pathophysiology of acute pancreatitis is that no matter the inciting event, there is an unregulated intra-acena activation of trypsin. leading to an autodigestive injury to the pancreas with local inflammation. So the protective intracellular mechanisms that prevent trypsinogen activation are overwhelmed.

And there's trypsin-mediated activation of pancreatic autodigestive enzymes, which also activate the complement and kinin pathways. This leads to local macrophage production of inflammatory mediators such as IL-1, 6, 8 and tumor necrosis alpha, leading to a cascade of endothelial cell activation. secondary tissue hypoxia, and release of free radicals. And you can insert the SERS pathophysiology answer here as well. What is the pathophysiology of chronic pancreatitis?

Chronic pancreatitis is a benign inflammatory disease characterized by chronic pancreatic inflammation and scarring. that irreversibly damages the gland and results in loss of pancreatic endocrine and exocrine function. And it's characterized by atrophy and fibrosis of the... tissue. What is the pathophysiology of chronic pain in chronic pancreatitis?

It's thought that the pathogenesis of pain and chronic pancreatitis is potentially quite complex and multifactorial, but there's probably a pancreatic component. related to inflammation of the gland and obstruction of the main pancreatic duct. And I've heard this described as almost a compartment syndrome of the pancreas. And there's also an extra pancreatic component related to abnormal neural pathways and an aberrant central nervous system perception of pain.

So let's finish off hepatobiliary with some spleen questions. What is the pathophysiology of ITP? And I got asked this in my written exam. The pathophysiology of ITP is autoantibodies against the membrane glycoproteins on the platelets that labels the platelets for destruction in the spleen. What is the pathophysiology of overwhelming post-splenectomy infection or OPSE?

The pathophysiology of opsy is that the spleen is involved in the opsonization of encapsulated organisms. And so in the absence of the splenic macrophages that... that attack and destroy these encapsulated organisms, the ability of the patient's body to fight off these pathogens is severely diminished. The other thing is that the spleen is also a major site of early

immunoglobulin M production, which is important in the acute clearance of pathogens from the bloodstream via opsonization. And so patients are at an increased risk of infections, specifically Streptococcus pneumonia, Haemophilus influenzae, and Neisseria meningitides. But there are a number of other bacteria and parasites that can also cause opsi.

Well I think that's enough for this first episode. Thanks so much for joining me. Please leave me a review, rate the podcast and subscribe. It makes it easier for others to find. And feel free to reach out with any other suggestions for episodes that you might find useful for your study. It's time to close up. Thanks for listening to First Incision. If you have any comments or feedback...

Send us a message at firstincisionpodcast at gmail.com or follow us on Instagram at firstincision. Happy studying!