Uploaded byajayyadav753
PPTX, PDF29 views

Gastrointestinal and Hepatic manifestations of Systemic Diseases -II.pptx

Hepatic and gastrointestinal manifestations may be the presenting diseases of various systemic diseases. It is necessary to know about these manifestations to timely diagnose and manage these systemic diseasesHepatic and gastrointestinal manifestations may indicate various systemic diseases. Understanding these symptoms is essential for the timely diagnosis and management of these conditions..

Download to read offline
Gastrointestinal and Hepatic manifestations of Systemic Diseases - II Dr. Ajay Kumar Yadav DM1 resident Gastroenterology 2080/11/30
Layout • Gastrointestinal and hepatic manifestations of Red Blood Cell Dyscrasias Endocrine Diseases Renal Diseases Cardiac Diseases Pulmonary Diseases Critical Illness and Sepsis Neurological Diseases Infiltrative diseases Heavy Metal Toxicity Disorders of Lipid Metabolism
Red Blood Cell Dyscrasias Sickle Cell Disease • AR abnormality of the β-globin chain of Hb  HbS polymerizes when deoxygenated  gelatinous network  stiffens the erythrocyte membrane and increases viscosity  micro-vascular occlusion  ischemia and infarction of the organs and RBC destruction • Splenic Involvement  First 6 months of life, splenic congestion and sickling  functional asplenia.  With repeated hemorrhages and infarctions occur spleen becomes smaller and is eventually replaced by fibrous tissue: autosplenectomy.  ↑susceptibility to infection with encapsulated bacteria  Radiologically, the spleen is small and often calcified
• Acute splenic infarction – more common in SC-HbC or SC thalassemia than in homozygous SCD – LUQ pain, N/V, splenic rub, occ. abscess, pseudocyst or rupture • Acute splenic sequestration – sudden pooling of blood in the spleen  rapid splenic enlargement and a drop in Hb. – In homozygous SCD, it occurs only in infants and children – In SC-thalassemia, can occur at any age
Fig. CT showing Splenic sequestration Fig. Complications of SCD
Biliary Tract Involvement • Cholelithiasis (70%) – Pigmented stones, chronic hemolysis, calcium bilirubinate, radiopaque • Choledocholithiasis (18 to 30%) • Sickle cholangiopathy – cholestatic jaundice w/o choledocholithiasis – d/t ischemic bile duct injury. Hepatic involvement • Acute sickle hepatic crisis – 10% of patients of painful crisis – stagnation of sickled cells in the hepatic sinusoids  decreased hepatic blood flow. – RUQ pain, N/V, tender hepatomegaly, low-grade fever, leukocytosis, and ↑AST/ALT(1-3×) and TB/DB • Acute hepatic sequestration – Lungs, spleen > liver – acute hepatic enlargement, rapid drop in Hct, ↑ reticulocyte count, and mild increase in liver enzymes and bilirubin
• Acute sickle intrahepatic cholestasis – rare, potentially fatal complication caused by widespread sickling in the sinusoids  hypoxia and intra- canalicular cholestasis. – severe form of hepatic crisis with severe hyperbilirubinemia, coagulopathy, and renal insufficiency/failure ultimately resulting in liver failure. • Acute hepatic failure – rarely occurs, usually in the presence of CLD • VOD (39%) • Liver abscesses – secondarily infected hepatic infarct • Miscellaneous GI Problems  Abdominal pain  a/w vaso-occlusive crisis  a/w pain elsewhere, such as in the limbs and chest  typically relieved with hydration and oxygen within 48 hours.  d/t small infarcts of the mesentery and abdominal viscera  Acute pancreatitis: not common  d/t GB stones, ischemic injury  Duodenal ulcers  d/t reduced mucosal resistance  Ischemic bowel
Hemosiderosis • With multiple BT and hemolysis in SCD • Pts with thalassemia: ↑BT requirement than SCD + ↑intestinal uptake of iron from ineffective erythropoiesis  more visceral iron loading. • On CT, the density of the liver and spleen increases with hemosiderosis. • On MRI, the magnetic signal diminishes in the liver as the iron concentration increases. – MRI T2 techniques correlate with hepatic iron content and can be used to guide therapy. • Ferritin is a poor measure of iron overload, because it is an APR • T/t: iron chelators: S/C deferoxamine, oral (deferiprone and deferasirox)
Coagulation disorders • Intramural hematomas – due to trauma or bleeding diatheses most commonly involve the duodenum (D2/3) or jejunum, respectively. • Von Willebrand Disease (VWD) – the most common inherited bleeding disorder – GI bleeding commonly occurs in a/w GI angioectasias or w/out visible lesions. • Heyde syndrome – calcific aortic valve stenosis + GI bleeding – acquired deficiency of VWF as the multimers are reduced in size from the shear stress. – AVR  corrects the abnormality – LVAD (30-40%)
Fig. Classification of VWD
Fig. Pathophysiology of acquired VWD in AS Fig. Calcified AS with GI angiectasias
GI manifestations • Cramping pain abdomen, N/V, bloody diarrhea • Rarely, pancreatitis, hemoperitoneum, colonic perforation, or stricture
ENDOCRINE DISEASES Diabetes Melitus  Cancer • a/w ↑ risk of certain GI malignancies: Pancreatic cancer, HCC, CRC • The association may be due in part to shared risk factors such as aging, obesity, diet, and physical inactivity. • Metformin may reduce the risk of cancer, whereas insulin may increase it. • Insulin resistance  secondary hyperinsulinemia  ↓IGFBP ↑IGF-1  stimulate cancer growth. • modest increase in pancreatic cancer with DM > 5 years • Chronic pancreatitis with pancreatic insufficiency increases the risk of both DM and pancreatic cancer • Pancreatic adenocarcinoma should be considered in an older patient with new-onset, poorly controlled DM, especially with weight loss
Metformin and cancer Hua et al. Journal of Translational Medicine (2023) 21:403 https://doi.org/10.1186/s12967-023-04263-8
Hua et al. Journal of Translational Medicine (2023) 21:403 https://doi.org/ 10.1186/s12967- 023-04263-8
Esophageal involvement • esophageal dysmotility (up to 50%), symptomatic only 25%. • Defects include decreased LES pressure, delayed transit, multi- peaked or spontaneous contractions, and reduced amplitude of contractions • Esophagitis (40%) • oral and esophageal candidiasis  dysphagia/odynophagia • predisposing factors: impaired immunity, esophageal stasis from dysmotility, and hyperglycemic impairment of neutrophil function and opsonization Gastric involvement • Gastroparesis • Type 1 DM  15% to 20% incidence of APCA, autoimmune atrophic gastritis (5% to 10%), and pernicious anemia (2.6% to 4%). • Autoimmune atrophic gastritis  IDA • ↑ risk for type I gastric carcinoids and probably gastric cancer. • association between DM and PUD: controversial – increases the risk of ulcer bleeding, perhaps secondary microangiopathy impair mucosal integrity. • no clear association between Hp and DM
Diabetic gastroparesis
Complications of Gastroparesis • Dehydration • Malnutrition • Fluctuating blood sugar
Small bowel involvement • Celiac disease: 4% (DM) Vs 0.5% (GP) – Predominant non-GI manifestations s/a short stature, pubertal delay, fat soluble vitamin deficiencies, anemia, osteoporosis, and/or reproductive disorders. • Type 1 DM with celiac disease – poor glycemic control, hypoglycemic episodes, and microvascular complications • Constipation > Diarrhea (up to 22%). • Diarrhea: often episodic, painless, and sometimes nocturnal, steatorrhea (uto 75%) • Metformin induced, even after years of t/t • Etiologies of diarrhea related to DM – drugs, fast transit, autonomic neuropathy, celiac disease, SBBO, excess use of sugar-free sweeteners, pancreatic insufficiency, and hormones • Neuropathy may cause diarrhea by altering fluid and electrolyte transport and by altering motility. • Treatment of diarrhea – t/t of specific etiology or loperamide. – Clonidine stimulates α2- adrenergic receptors but may worsen orthostatic hypotension. – Octreotide, or the long-acting octreotide analog lanreotide may help
Colonic and anal involvement • Constipation (>50%) – long-standing DM impaired gastrocolic reflex and delayed colonic transit. • Occasionally, megacolon and (rarely) intestinal pseudo- obstruction • Ischemic colitis • Fecal incontinence a/w dysfunction of the IAS and/or reduced sensitivity of the rectum to distension. GB involvement • Possible causes of GB dysfunction  defect in the cholinergic pathway,  reduced α-adrenergic tone,  deficiency of CCK receptors,  arteriolar disease impairing muscle contraction,  hyperglycemia, and hyperinsulinemia. • Risk of GB stones: controversial, common risk factors • Emphysematous cholecystitis  Peculiar with DM  probably due to ischemia of the GB from vascular compromise, with proliferation of gas-forming organisms.
Fig. Emphysematous Cholecystitis. CT abdomen shows gas within the wall of the gallbladder (horizontal arrow) as well as within the lumen of the gallbladder (vertical arrow). Fig. Emphysematous cholecystitis. X-ray abdomen erect shows gas within lumen (arrow) as well as within wall of GB (arrowhead)
Pancreatic involvement • DM  pancreatic insufficiency d/t vasculopathy + autonomic neuropathy with impaired enteropancreatic reflexes. • T1DM: autoimmune processdamage both endocrine β cells and adjacent exocrine cells + low insulin level reduced trophic effects on acinar cells. • CP, Pancreatic cancer, hemochromatosis, AP, partial pancratectomy  T3cDM – ↑hypoglycemic episodes, rare DKA • ↑ed incidence of AP, a risk that is reduced by taking antidiabetic drugs. • AP can complicate DKA in 11% of cases; transient hypertriglyceridemia is thought to be a contributing factor. – may worsen volume depletion and hyperglycemia a/w DKA. • DKA itself can be a/w abdominal pain and mild elevations of amylase and lipase without pancreatic inflammatory changes
Hepatic involvement • Abnormal LFT common in T2DM, esp. serum ALT. – If ALT < 3 UNL and no cause found, oral antidiabetic and statins can be started • Hepatitis or ALF has been a/w thiazolidinediones, and cholestasis with sulfonylureas. – Metformin has not been a/w hepatotoxicity. • MASLD common in DM, is a manifestation of insulin resistance, often found in conjunction with the metabolic syndrome. • DM has been shown to ↑ the risk of ALF independent of underlying liver d/s • Cross-sectional and longitudinal studies: HCV ↑ risk of T2DM(OR 1.6 to 2.1) – Similarly, HCV is a strong predictor of new-onset DM after LT – HCV eradication improves insulin sensitivity and reduces the incidence of DM.
Fig. New nomenclature of NAFLD by AASLD
Hepatogenous diabetes • 30% to 60% of cirrhotic patients • characterized by insulin resistance in muscular, hepatic, and adipose tissues, as well as hyperinsulinemia and an impaired response of pancreatic islet cells. • reduced frequency of micro- and macroangiopathic complications, perhaps d/t lower BMI, lipids, and BP compared to T2DM. • ↑risk for hypoglycemia due to minimal glycogen storage in the liver, impaired hepatic insulin extraction, high catabolic rate, and sometimes superimposed alcoholism. • Should generally have no dietary restrictions, because they are often malnourished. • Oral hypoglycemic drugs are metabolized by the liver, so may lead to hypoglycemia. – Although metformin reduce insulin resistance, it is relatively contraindicated d/t risk of lactic acidosis in cirrhotic patients who drink alcohol. • LT cures DM in 67% of cirrhotic-diabetic patients.
Fig. Pathophysiology of Hepatogenous diabetes in cirrhotic liver
Thyroid Disease Hyperthyrodism • Clinical manifestations: apathetic thyrotoxicosis  thyroid storm • GI symptoms: abdominal pain, N/V, LOW, and diarrhea. • may be a/w other autoimmune diseases s/a pernicious anemia, celiac disease, and UC. • Dysphagia: rare – direct compression from a goiter or nodule, – Excess hormone  myopathy affect striated muscles of pharynx and upper 1/3rd esophagus, – increased esophageal contraction velocity. • Gastric emptying: normal, rapid, or delayed • Diarrhea (up to 25% of pts) – Accelerated transit time + dietary fat hyperphagia  steatorrhea
• Diarrhea may decrease with propranolol, suggesting improvement of a relative adrenergic stimulatory state • Mild abnormalities in serum aminotransferases or ALP, clinically significant abnormalities rare – d/t thyroid dysfunction itself, or drug therapy (PTU), or concomitant (AIH and PBC) • Severe cholestatic hepatitis, jaundice, and/or ALF: rare – d/t mismatch between increased hepatic oxygen consumption and hepatic blood flow. – Predominant zone 3 hepatic necrosis with or without concomitant RHF typical.  t/t: Anti-thyroxine + emergent thyroidectomy and/or LT
Hypothyrodism • most commonly d/t Hashimoto’s thyroiditis or to thyroid ablation for hyperthyroidism. • a/w UC, pernicious anemia, DM, celiac disease, and PBC. • Cl/f: constipation, anorexia, N/V, and abdominal pain. • Esophageal manifestations: dysphagia and reflux, d/t motility disorder with low LES pressure and reduced amplitude of contractions. • Gastric manifestations: reduced acid secretion or delayed gastric emptying, phytobezoars • Small/large bowel manifestations – SBBO – SI transit time may be normal or delayed – Colonic hypomotility  obstipation, ileus, megacolon, or volvulus. • Pathology: neuropathy or accumulation of GAGs in the interstitial tissues. • Ascites in myxedema: – high protein (>2.5 g/dL) with a variable SAAG, and a low TLC with a predominance of lymphocytes. – Resolution occurs with thyroid replacement, not with diuretics.
Medullary Carcinoma of the Thyroid (MTC) • calcitonin-producing tumor of the C cells of the thyroid gland. • Sporadic (80%) or Familial (20%, MEN-II). • Diarrhea: 1/3rd patients, particularly in those with extensive mets • ↑calcitonin,PGs, 6-HIAA, or histamine Fig. MTC. Notice the bands of amyloid (thick arrow) interspersed between nests of tumor cells
Parathyroid Disease Hyperparathyrodism • GI complaints: constipation (large bowel atony), N/V (gastric atony), anorexia, and weight loss. • Abdominal pain d/t: PUD, pancreatitis, or atony. • Gastric acid hypersecretion and/or hypergastrinemia have been found in some but not other studies. • Constipation may be due to a reduction in neuromuscular excitability by high calcium levels • Incidence of AP: 1% to 12%; Pancreatic calculi, mainly intraductal: 80% – T/t: Parathyroidectomy
Hypoparathyrodism • The main GI manifestation is steatorrhea. – d/t insufficient CCK release and pancreatic enzyme secretion. • Replacement of dietary LCTG with MCTG  reduces fecal fat losses fecal calcium losses from saponification • Occ. a/w celiac disease – Underlying celiac disease s/b suspected even in the absence of diarrhea in a hypoparathyroid pt whose serum calcium levels do not respond to t/t. • May cause a low serum ALP but zinc deficiency, magnesium deficiency s/b considered as well.
Adrenal Disease Addison’s Disease (AD) • GI symptoms (>50% ): N/V, diarrhea, and pain abdomen • A/w celiac disease (8% to 12%) - similar HLA associations. • Poor absorption of glucocorticoids d/t associated celiac disease may complicate the therapy of AD whereas glucocorticoid t/t may mitigate celiac sprue. • Atrophic gastritis and pernicious anemia may also be present. • ↑ serum aminotransferases resolve on glucocorticoid replacement therapy. Pheochromocytoma • GI manifestations: N/V, abdominal pain and, less commonly, constipation, ileus, megacolon, ischemic colitis, and perforation. • Catecholamines  decrease intestinal motility and tone by relaxation of intestinal smooth muscle + ischemia from vasoconstriction of splanchnic arterioles. • The effects can be relieved by α- adrenergic blockers - phentolamine. • Hypertensive emergencies can occur with the use of opioids and other medications (as during endoscopic procedures).
Pituitary Disease • The hypothalamic-pituitary-adrenal axis provides an important link between the brain and the gut (Brain-gut axis) • Pituitary disorders infrequently affect the GI tract, except in a/w MEN-I syndrome. • Hypercortisolism ↑increased incidence of GU with concomitant NSAIDs • Acromegaly a/w – increased length and circumference of the colon and slow colon transit time  standard bowel preparation often inadequate. – ↑risk of CRC, colonic polyps, and other GI tract cancers. • ↑ GH and IGF-1  epithelial cell proliferation • Octreotide t/t ↑GB stone formation – Symptomatic gallstone disease may occur following withdrawal of octreotide.
Renal Diseases • Anorexia, N/V, abdominal pain, and constipation are common – N/V: d/t DDS, uremic toxins, hypotension, and rapid changes in osmolality. – GER occurs, particularly in those undergoing PD • Gastric dysfunction may be a/w impaired gastric myoelectric activity, increased levels of GI hormones (e.g., CCK, gastrin) that modulate GI motility, uremic toxins, DM, autonomic nerve dysfunction, and the physical restriction caused by PD • Gastroduodenal lesions—usually inflammation, erythema, and erosions—are common • Prevalence of Hp infection: normal or reduced • Occult and overt GI bleeding: common – d/t uremia, platelet dysfunction and antiplatelet agents, NSAIDs, and/or heparinization during HD – ↑prevalence of angiectasias in the upper or lower GI tract
• Acute mesenteric ischemia – non-occlusive, may be d/t episodes of hemodynamic instability during HD. – Rt > Lt sided colon or multiple areas – poor prognosis. – Risk factors: NSAID use and aggressive EPO administration. • Constipation and fecal impaction: HD > PD – Constipation: inactivity, dehydration, reduced fiber intake, metabolic abnormalities, phosphate binders, aluminum antacids, ion exchange resins, comorbidities, and prolonged colonic transit – Diarrhea: SBBO from small bowel dysmotility, abnormal bile acid metabolism, exocrine pancreatic insufficiency, or amyloidosis • Oral sodium phosphate used as a bowel preparation  phosphate nephropathy, hyperphosphatemia, hypocalcemia, hypokalemia, and/or hyper- or hyponatremia • Is PEG safe in CKD? – PEG is an isosmotic solution that passes through the bowel without absorption or secretion. – Studies have shown that PEG is safe in patients with CKD
• GI necrosis may occur with sodium polystyrene sulfonate (Kayexalate), commonly used to treat hyperkalemia, in combination with sorbitol to prevent constipation. • Aluminum-containing antacids or sucralfate  aluminum toxicity or fecal concretions  obstruction and/or perforation. • Pts on HD ↑risk of perforation during colonoscopy, d/t deposition of β2-microglobulin ≈GI amyloidosis • Peritonitis related to the dialysis catheter in pts on PD is most commonly caused by a single organism and usually resolves with appropriate antibiotics. – Non-resolving peritonitis: polymicrobial pathogens + increase in effluent amylase concentration suggest bowel perforation, delayed diagnosis  ↑mortality • Sclerosing peritonitis – rare and lethal condition in PD – characterized by peritoneal thickening that encapsulates the bowel, causing obstruction. – CT abdomen: peritoneal thickening and calcification, loculated fluid collections, and adherent small bowel loops
• Hernias: common in pts on PD, esp. at the catheter insertion site, inguinal canal, umbilicus, and sites of previous surgeries. • Whether the incidence of acute pancreatitis is increased HD is controversial. • Macro-amylesemia Fig. CT showed diffuse parietal and visceral peritoneal calcifications encasing the small-bowel loops (arrows), consistent with encapsulating peritoneal sclerosis.
Pulmonary Diseases Bronchial Asthma • GERD: 3/4th of pts – worsened by the use of asthma medications (theophylline, β‐ agonists)↓LES • Worsened wheezing: reflex bronchial constriction > aspiration of gastric contents • Chronic idiopathic cough is commonly a/w GERD • Even in the absence of heartburn, acid may trigger nocturnal cough or laryngospasm COPD • a/w PUD • risk for GU appears to increase with the number of cigarettes smoked per day. • ↑ed mortality a/w perforated or bleeding ulcers, especially with use of glucocorticoids
α 1 Antitrypsin deficiency ‐ ‐ • autosomal co-dominant disease • GI manifestations: CLD, cirrhosis, and HCC
Cystic fibrosis • most common genetic illness among Caucasians, with an incidence of about 1 per 2500 • Mutations in CFTR on chromosome 7q defect in mucosal cAMP ion and water transport • GI manifestations: distal intestinal obstruction (adults), meconium ileus (infants) • Gastroesophageal reflux may enhance the pulmonary symptoms – Contributing factors: ↓LES tone + ↓saliva production + GI hypomotility + chronic cough • Pancreatic insufficiency • Protein–calorie malnutrition • Prolonged pancreatic enzyme supplementation  fibrosing colonopathy – bloody diarrhea a/w diffuse narrowing of the colon (mostly the right colon) with rectal sparing • Clinically apparent liver disease usually develops during or before puberty with a prevalence of 13–17%. • Focal biliary cirrhosis progressive portal hypertension (10%) • ↑GI mallignacies + non-GI cancers, including kidney, thyroid, endometrial, lymphoma, NMSCC
Critical illness and Sepsis • Frequent upper GI dysmotility  high gastric residual volumes, abdominal distension, N/V, regurgitation, and aspiration. • Bacterial colonization of the upper airways (may originate from flora in stagnant gastric contents) pneumonia • Low to absent LES pressure +↓ esophageal contractions + diminished saliva + frequent straining (usually coughing from ET suctioning)  reflux and aspiration. • Acute stress-induced gastropathy: common, with hemorrhage ↑ed in pts on MV and those with significant coagulopathies. • Constipation (no bowel movement in the first 96 hours in the ICU): 50% – main risk factors: opioid intake and disease severity. – Fiber laxatives s/b used with caution  fecal impaction (if fluid intake inadequate). • Ischemic colitis: following hypotensive episodes. • Acalculous cholecystitis: manifests as acute abdominal pain, unexplained leukocytosis, or abdominal sepsis.
Fig. Pathogenesis of acute stress-ulcer
• Hepatic involvement in sepsis is the most common cause of jaundice in ICU patients. – Phase 1: hepatic hypoperfusion ↓ synthetic function of the liver – Phase 2: liver response to sepsis as the major protective organ. • Pts with cirrhosis: ↑hospitalizations a/w sepsis and an ↑ed likelihood of death from sepsis. • LFT abnormalities: – Peak TB/DB: usually 5- 10 mg/dL – SALP: ↑ed in 50% pts; rarely ≥ 2 to 3 times UNL – Serum aminotransferases: usually normal but can be slightly elevated. – Serum albumin: may be low but no lower than in non-jaundiced sepsis. • Bile duct injury from sepsis and trauma  progressive sclerosing cholangitis, usually small duct disease. – s/b considered with persistent hyperbilirubinemia and elevated serum ALP levels after resolution of the sepsis • No specific treatment for hepatic involvement in sepsis indicated. • Prognosis is unrelated to hepatic involvement or to the height of the hyperbilirubinemia in pts with sepsis, but rather to the underlying process.
Cardiovascular Diseases • Cardiac diseases affecting liver  congestive hepatopathy, ischemic hepatopathy, or even cardiac cirrhosis with ascites. • Liver diseases affecting lungs and heart  HPS, PPH, pericardial effusions CCM, and high-output failure • Diseases affecting both the liver and the heart/circulation include sepsis and infiltrative disorders s/a hemochromatosis, amyloidosis, and sarcoidosis. • Heart disease (HF, CCP, cor pulmonale)  intestinal malabsorption/PLGE. • Ischemic heart disease  risk factor for ischemic colitis • Symptomatic GI angiectasias may occur in pts with AS (Heyde syndrome) and 30%-40% after LVAD
NEUROLOGIC DISEASES Abdominal epilepsy • rare condition, children > adults. • characterized by 1) paroxysmal GI complaints, usually abdominal pain, N/V of unclear etiology; 2) symptoms of a CNS disturbance, usually lethargy and confusion; 3) abnormal EEG indicating a seizure disorder; and 4) sustained improvement with AED  Temporal lobe involvement • Head trauma  stress gastropathy and delayed gastric emptying • Stroke – pharyngeal dysphagia (brainstem lesion) – stress gastropathy – Constipation: d/t prolonged colonic transit time, immobility, and altered diets
Diseases of the CNS Abdominal migraine • children (1-4%) > adults, F>M T/t: 1. Non-pharmacologic therapy: removal of triggers 2. Antimigraine therapies may be successful
Multiple sclerosis (MS) • most frequent chronic neurologic disease in young persons in developed countries. • GI disturbance: 40% of MS pts – constipation and fecal incontinence – early satiety, N/V , – postprandial discomfort a/w delayed gastric emptying. • ↑prevalence of celiac disease • Constipation: a/w – prolonged colonic transit time, – pelvic floor dysfunction, – reduced colonic compliance, – immobility, – paradoxical anal contractions, – absence of postprandial colonic motor – medications (anti-cholinergics, opiates) • Defecography: – pelvic outlet obstruction with failure of the puborectalis and anal sphincter muscles to relax • Fecal incontinence in MS – d/t reduced EAS tone, reduced anorectal sensation, and spontaneous rectal contractions.
Spinal Cord Injury (SCI) • Usually present with constipation, abdominal pain, distension, bowel accidents, and autonomic hyper-reflexia • Spinal shock occurs for several weeks after the injury – all autonomic and reflex activities are lost below the level of injury. • Abdomen: distended and flaccid, with no sensation below the level of injury and with absent or hypoactive bowel sounds d/t gastric dilatation and a paralytic ileus. – Incidence of PUD and hemorrhage: ↑ed. • Spinal shock ends  return and then exaggeration of autonomic reflex activity below the level of injury. • SCI lies above T6  autonomic hyperreflexia  intense reflex vasoconstriction of splanchnic blood flow  hypertension, diaphoresis, bladder spasms, and diarrhea.
• The diagnosis of an acute abdomen may be delayed in a high-level SCI • Abdominal operations are challenged by deformities or spasticity. • Hyper-reflexic HTN, ↓pulmonary excursion, prolonged ileus, and chronic septic foci: ↑risk of wound infections. • ↑GER: supine position, ↑ IAP d/t constipation • Gastric emptying: either delayed or normal – Promotility agents effective (intact ENS) • Fecal impaction/constipation (esp with SCI above T7) < Fecal incontinence, megacolon, stercoral ulcers, and hemorrhoids • First 6 months after SCI: biliary sludge > GB stones, > 6 months, the prevalence of GB stones is high (17% to 31% of SCI patients)
SMA syndrome (Wilkie’s syndrome, cast syndrome) • D3 is intermittently compressed by the overlying SMA • May occur following rapid weight loss, prolonged supine positioning, and the use of spinal orthoses. • Intermittent or PP epigastric pain f/b billious volmiting  pain relieved by prone, knee-chest, left lateral position or Hayes maneuver
Extrapyramidal (Movement) Disorders • Hypokinetic (PD) and Hyperkinetic (HD) • Lewy bodies, the pathognomonic feature of PD, are found in the ENS of the esophagus, stomach, and colon. • Dopaminergic deficiency in the ENS and involvement of the DMN of vagus ↓ parasympathetic innervation to much of the GI tract • In PD, saliva is excessive, from reduced effectiveness of swallowing. • All stages of swallowing—oral, pharyngeal, or esophageal—may be affected by PD • Delayed gastric emptying, particularly of solids  Gastroparesis may interfere with levodopa  Metoclopramide is C/I: aggravates PD by blocking central dopamine receptors, Dopamine - safe
• Gastritis caused by Hp may interfere with levodopa absorption; an improved response to levodopa occurs after its eradication. • Constipation: Frequent, even before PD  Medications + reduced mobility + weak abdominal straining  Prolonged orocecal transit time + dys-synergia d/t dystonia (may prevent the EAS from relaxing)  T/t: BOTOX, Apo-morphine • Rarely, megacolon, pseudo-obstruction, volvulus, or even perforation • Huntington disease (HD)  AD neurodegenerative disease characterized by involuntary movements, psychiatric disturbance, and cognitive decline.  Dysphagia in HD occurs in the preparatory oral phase (postural instability, tachyphagia, poor lingual control), the oral phase, the pharyngeal phase, or esophageal phase.
GI symptoms seen in 85% of pts of autonomic dysfunction/diseases
Disease of the NMJ Myasthenia gravis: • Characterised by fatiguable muscle weakness. • Dysphagia and aspiration: common Pharynx and upper 1/3rd esophagus involved. Classically, contractions weaken with repetitive swallows • may be a/w other autoimmune diseases such as pernicious anemia, AIH, or PBC. Muscular Dystrophy • DMD – mutation of the dystrophin gene  abnormal dystrophin (skeletal muscle > smooth muscle, myenteric neurons) • Myotonic MD: Most of the GI tract involved • Oropharyngeal symptoms: typical, may lead to aspiration • Delayed gastric emptying + reduced postprandial ↑ in motilin levels  Early satiety, N/V, epigastric pain, and/or bezoars. • Episodic severe diarrhea, malabsorption, and fecal incontinence
INFILTRATIVE DISEASES Amyloidosis • group of infiltrative disorders that result from the extracellular deposit of amyloid fibrils
Fig. Systemic manifestations of Amyloidosis
Oral, Esophageal, and Gastric Involvement • Macroglossia: pathognomonic  dry, fissured, ulcerated, and indented by teeth  airway obstruction, speech difficulties, oral dysphagia, and malocclusion of teeth. • Esophagus: 13% (radiologic study) and 22% (autopsy)  dysphagia, chest pain, heartburn, and hematemesis.  Basal LES pressure: normal or low, amplitudes of esophageal contractions: ↓ed • Involvement of the submandibular gland  xerostomia • Gastric involvement : 12% (autopsy) and 8% (endoscopy)  Only 1% symptomatic: Early satiety, N/V, abdominal pain, or hematemesis.  GOO  Gastroparesis, esp. with familial amyloidotic polyneuropathy  Loss of rugal folds and decreased motility when smooth muscle is replaced by amyloid.  EGD: granular appearance, friability, polyps, erosions/ulcers, and enlarged folds
Small and Large Bowel Involvement Small Bowel (most involved):  diarrhea, steatorrhea, PLGE, hemorrhage, obstruction, ischemia and infarction, pneumatosis cystoides intestinalis, intussusception, constipation, pseudoobstruction, mesenteric infiltration, and perforation  Thickened folds (d/t amyloid in the vasculature)  ischemic enteritis, amyloid in the wall, or hypoalbuminemia.  Hypoalbuminemia results from malabsorption, PLGE, and/or nephrotic syndrome Large bowel involvement  May mimic IBD, malignancy, or ischemic colitis.  Diarrhea may be d/t autonomic dysfunction, delayed, SBBO, bile acid malabsorption, pancreatic insufficiency  Steatorrhea: common in FAP but not AL amyloidosis.  Hemorrhage d/t: direct vascular and tissue infiltration ↑ed friability or ischemia + impaired vasoconstriction.  Prolonged PT: d/t liver dysfunction, malabsorption, ↓vitamin K intake, or ↓FX.  Amyloidosis occurs clinically in 0.9% of pts with CD and in 0.07% of pts with UC
Hepatic Involvement • Hepatic amyloidosis has no clinical significance, except in FAP • When symptomatic: weight loss, fatigue, abdominal discomfort, and anorexia. • Ascites is more often due to cardiac failure than to liver disease. • Stigmata of CLD: uncommon. – Splenomegaly is usually a/w hepatomegaly – Hyperbilirubinemia is a/w poor prognosis.
Granulomatous Liver Disease • MCC  Developed world: PBC  Developing world: TB • Clinical manifestations of hepatic granulomas  asymptomatic > symptomatic (hepatomegaly, RUQ pain, fever, and/or weight loss) Sarcoidosis • multisystem granulomatous disorder of unknown cause. • ↑ed incidence and mortality in African Americans > Caucasians. • constitutional symptoms, lung disease, adenopathy, uveitis, proximal myopathy, lupus pernio, CN palsies, EN, hypercalcemia, and granulomas in many organs
Fig. Clinical manifestations of Sarcoidosis
Gastrointestinal Involvement (rare) • Esophagus: rarely involved  Dysphagia or reflux.  Mucosal involvement: aphthous lesions, plaques, or nodules.  NM involvement: dysmotility in the cricopharynx or achalasia-like picture responding to glucocorticoids • Stomach: m/c GI site involved  usually asymptomatic > N/V, early satiety, abdominal pain. • Duodenal involvement from sarcoidosis is rare. • Ascites is rare and usually due to RHF or PHTN. – However, peritoneal studding with small nodules may cause a lymphocytic ascites • There may be an association between celiac disease and sarcoidosis ≈ both linked to HLA-DQ2 and HLA-DR3 • Pancreatic sarcoidosis: quite rare  Presentation: enlarged pancreas, biliary obstruction, abdominal pain, AP, or pancreatic insufficiency • Acute cholecystitis:  secondary to extrinsic compression of the cystic duct by lymph nodes or by granulomatous inflammation of the GB. • Obstructive jaundice:  granulomatous involvement of the bile ducts or surrounding lymph nodes.
Sarcoidosis VS Crohn’s Disease (CD)  Distinguishing features suggesting Sarcoidosis: rare Schaumann bodies, granulomas outside the GI tract, and a dramatic response to glucocorticoids.  Fistulas, architectural distortion, and acute inflammation: uncommon Sarcoidosis Vs Lymphoma • Unlike lymphoma, abdominal adenopathy in sarcoidosis is characterized by lymph nodes that are generally < 2 cm in diameter, discrete (rather than confluent), and spare the retro-crural area.
Hepatic and Splenic Involvement • Hepatic involvement: asymptomatic > pain abdomen (m/c) > jaundice (rare) • Jaundice is d/t intrahepatic cholestasis, hemolysis, hepatocellular dysfunction, or obstruction of the EHBD by enlarged lymph nodes. • Cholestasis may be d/t sarcoidosis of EHBDs, bile duct compression by enlarged perihilar lymph nodes, involvement of the pancreas, or associated PBC and PSC. • Unlike PBC and PSC, pts with sarcoidosis usually have normal serum IgM levels, negative AMA, and negative ANCA. – In addition, they may have rapid improvement with glucocorticoids not seen with PBC or PSC. • Because cirrhosis is rare and liver function is usually preserved, encephalopathy and liver failure are unusual. • Splenic involvement: asymptomatic > LUQ abdominal pain, constitutional symptoms, hypersplenism, and rarely rupture.
HEAVY METAL TOXICITY
Lead Poisoning • s/b considered in pts with abdominal complaints and a history of occupational or environmental exposure, s/a ingestion or removal of lead‐ based paints, manufacture of batteries or jewelry, welding • Common symptoms include recurrent severe abdominal pain (lead colic), oral ulcers, constipation, stocking–glove paresthesias, psychiatric symptoms, and a metallic taste in the mouth.
DISORDERS OF LIPID METABOLISM Hypertriglyceridemia • TG > 1000 mg/dl  acute and recurrent pancreatitis but rarely CP • Usually the pt has a familial hyperlipoproteinemia (Type IV) along with secondary factor, s/a poorly controlled DM, alcohol intake, or use of medications s/a estrogen. • The serum amylase level may be normal or minimally elevated Fabry disease • X-linked deficiency of α-galactosidase A • GI symptoms: abdominal pain and diarrhea (50% to 60%) • may be confused with IBS-D • Gastroparesis, N/V, autonomic neuropathy, bowel dilatation, formation of diverticula, reduced peristalsis, and SBBO
Gaucher disease • deficiency of glucocerebrosidase • characteristic Gaucher cells: macrophages engorged with lipid with a crumpled tissue paper appearance • Hepatosplenomegaly: common. • Hepatocytes are spared  liver failure is uncommon. • Portal hypertension: uncommon, d/t splenic enlargement and/or to intrahepatic obstruction from extensive deposits of Gaucher cells Niemann-Pick disease type B • deficiency of acid sphingomyelinase • characterized by accumulation of sphingomyelin within lysosomes, mainly in monocytes/macrophages. • Portal hypertension, liver failure, and cirrhosis are uncommon Fig. Gaucher cells with crumpled tissue appearance
Tangier disease • AR disorder characterized by accumulation of cholesterol esters in macrophages in tonsils, thymus, lymph nodes, marrow, liver, and the gut. • Mutation in the ATP-binding cassette protein (ABCA1)  mediates the efflux of excess cellullar sterol to apolipoprotein A-I  HDL. • The striking clinical findings include yellow-orange “streaked” tonsils (80% ), hepatosplenomegaly, and peripheral neuropathy. • Diarrhea w/out steatorrhea. Colonoscopy: orange-brown mucosal spots throughout the colon and rectum,
LYSOSOMAL STORAGE DISEASES
References • Sleisenger and Fordtran’s Gastrointestinal and Liver Disease 11th Edition • Yamada’s Textbook of Gastroenterology 7th Edition

More Related Content

PPTX
Gastrointestinal Pathophysiology
byDana Luery
 
PPTX
9-Gastrointestinal and hepatobiliary function.pptx
byAbdallahAlasal1
 
PPTX
Diabetes and GIT
byVadivel Kumaran Sivasankaran
 
PPTX
Diabetes and GIT
byVadivel Kumaran Sivasankaran
 
PPTX
DIABETES AND GASTROINTESTINAL TRACT
byVadivel Kumaran Sivasankaran
 
PPTX
DIABETES AND GASTROINTESTINAL TRACT
byVadivel Kumaran Sivasankaran
 
PPTX
GASTRIC ANTRAL VASCULAR ECTASIA
bySravan Kumar Jogu
 
PPT
16-Disorder of gallbladder and pancreas(6).ppt
byekakacina
 
Gastrointestinal Pathophysiology
byDana Luery
 
9-Gastrointestinal and hepatobiliary function.pptx
byAbdallahAlasal1
 
Diabetes and GIT
byVadivel Kumaran Sivasankaran
 
Diabetes and GIT
byVadivel Kumaran Sivasankaran
 
DIABETES AND GASTROINTESTINAL TRACT
byVadivel Kumaran Sivasankaran
 
DIABETES AND GASTROINTESTINAL TRACT
byVadivel Kumaran Sivasankaran
 
GASTRIC ANTRAL VASCULAR ECTASIA
bySravan Kumar Jogu
 
16-Disorder of gallbladder and pancreas(6).ppt
byekakacina
 

Similar to Gastrointestinal and Hepatic manifestations of Systemic Diseases -II.pptx

PPTX
MCS 300 Abdomen and GasTrointestine .powerpoint
bytaongachikunyu
 
PPT
Gastroenterology Tutorial
bymeducationdotnet
 
PDF
Core cases in Gastroenterology
byAnahita Sharma
 
PPTX
Celiac common presentation of a uncommon disease saved with date
byMuhammad Arshad
 
PPTX
Upper GI bleeding
byAhmed Almakrami
 
PDF
Git
byEpah Zulkifli
 
PPTX
GIT bleeding.pptx is a very good, precise and conscise note prepared for heal...
bynyakthok07
 
PPTX
Liver in systemic disease
byAhmed Abudeif
 
PPTX
approach to ascites and abdominal swelling
byDR Venkata Ramana
 
PPTX
Diagnosing diabetes
byJO de la Cruz
 
PPTX
GIT CLINICAL CASES.pptx
byDavidKamau27
 
PPTX
NIKHILESH CHOUDHURY pdf of ppt 2023.pptx
byAyanshSarki
 
PPT
Diseases of git
byraj kumar
 
PPT
17 gi
byReach Na
 
PPT
Diagnosis & Management of Chronic Liver Disease.ppt
byKhooChunYik
 
PPTX
Approach to Management of Upper Gastrointestinal (GI) Bleeding
byArun Vasireddy
 
PPTX
CASE PRESENTATIONS;.pptx
byDavidKamau27
 
PPT
Git J Club Dm Git
byShaikhani.
 
PDF
Internal Medicine Board Review - Gastroenterology Flashcards - by Knowmedge
byKnowmedge
 
PPTX
Diabetic Cardiomyopathy 2.pptx
byshivaranjani54
 
MCS 300 Abdomen and GasTrointestine .powerpoint
bytaongachikunyu
 
Gastroenterology Tutorial
bymeducationdotnet
 
Core cases in Gastroenterology
byAnahita Sharma
 
Celiac common presentation of a uncommon disease saved with date
byMuhammad Arshad
 
Upper GI bleeding
byAhmed Almakrami
 
Git
byEpah Zulkifli
 
GIT bleeding.pptx is a very good, precise and conscise note prepared for heal...
bynyakthok07
 
Liver in systemic disease
byAhmed Abudeif
 
approach to ascites and abdominal swelling
byDR Venkata Ramana
 
Diagnosing diabetes
byJO de la Cruz
 
GIT CLINICAL CASES.pptx
byDavidKamau27
 
NIKHILESH CHOUDHURY pdf of ppt 2023.pptx
byAyanshSarki
 
Diseases of git
byraj kumar
 
17 gi
byReach Na
 
Diagnosis & Management of Chronic Liver Disease.ppt
byKhooChunYik
 
Approach to Management of Upper Gastrointestinal (GI) Bleeding
byArun Vasireddy
 
CASE PRESENTATIONS;.pptx
byDavidKamau27
 
Git J Club Dm Git
byShaikhani.
 
Internal Medicine Board Review - Gastroenterology Flashcards - by Knowmedge
byKnowmedge
 
Diabetic Cardiomyopathy 2.pptx
byshivaranjani54
 

More from ajayyadav753

PPTX
Small Bowel Bleeding: approach and management
byajayyadav753
 
PPTX
Hepatocellular carcinoma: From diagnosis to emerging therapeutics
byajayyadav753
 
PPTX
The Promise and Pitfalls of JAK Inhibitors in Inflammatory Bowel Disease
byajayyadav753
 
PPTX
INTESTINAL PARASITES- Trematodes, Cestodes, and Nematodes,
byajayyadav753
 
PPTX
Infectious enteritis and food poisoning.pptx
byajayyadav753
 
PPTX
HYPERGASTRINEMIA AND ZOLLINGER ELLISON SYNDROME.pptx
byajayyadav753
 
PPTX
Management of Ulcerative Colitis: Adjunctive therapies, Surgical management, ...
byajayyadav753
 
PPTX
Paradigm shift in IBD-UC management.pptx
byajayyadav753
 
PPTX
Diagnosis and Management of Hepatitis-B.pptx
byajayyadav753
 
PPTX
HEREDITARY AND FAMILIAL PANCREATITIS.pptx
byajayyadav753
 
PPTX
Gastrointestinal and Hepatic manifestations of Systemic Diseases-I.pptx
byajayyadav753
 
PPTX
Evaluation and approach to acute abdominal pain.pptx
byajayyadav753
 
PPTX
Diabetic Kidney Disease (DKD): Updates and management.pptx
byajayyadav753
 
PPTX
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.pptx
byajayyadav753
 
PPTX
SICKLE CELL ANEMIA: Clinical features, pathophysiology and management.pptx
byajayyadav753
 
PPTX
Benign anorectal disorders: Hemorrhoids, anal fissure, SRUS, Perianal abscess...
byajayyadav753
 
PPTX
VIDEO CAPSULE ENDOSCOPY (VCE): Introduction, Evolution, Indications
byajayyadav753
 
PPTX
High Resolution Manometry ccv 4.0 on Esophageal motility disorders.pptx
byajayyadav753
 
PPTX
Gastrointestinal and hepatic disorders in pregnancy.pptx
byajayyadav753
 
PPTX
Endoscopic Retrograde Cholangiopancreatography (ERCP): overview and technique...
byajayyadav753
 
Small Bowel Bleeding: approach and management
byajayyadav753
 
Hepatocellular carcinoma: From diagnosis to emerging therapeutics
byajayyadav753
 
The Promise and Pitfalls of JAK Inhibitors in Inflammatory Bowel Disease
byajayyadav753
 
INTESTINAL PARASITES- Trematodes, Cestodes, and Nematodes,
byajayyadav753
 
Infectious enteritis and food poisoning.pptx
byajayyadav753
 
HYPERGASTRINEMIA AND ZOLLINGER ELLISON SYNDROME.pptx
byajayyadav753
 
Management of Ulcerative Colitis: Adjunctive therapies, Surgical management, ...
byajayyadav753
 
Paradigm shift in IBD-UC management.pptx
byajayyadav753
 
Diagnosis and Management of Hepatitis-B.pptx
byajayyadav753
 
HEREDITARY AND FAMILIAL PANCREATITIS.pptx
byajayyadav753
 
Gastrointestinal and Hepatic manifestations of Systemic Diseases-I.pptx
byajayyadav753
 
Evaluation and approach to acute abdominal pain.pptx
byajayyadav753
 
Diabetic Kidney Disease (DKD): Updates and management.pptx
byajayyadav753
 
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.pptx
byajayyadav753
 
SICKLE CELL ANEMIA: Clinical features, pathophysiology and management.pptx
byajayyadav753
 
Benign anorectal disorders: Hemorrhoids, anal fissure, SRUS, Perianal abscess...
byajayyadav753
 
VIDEO CAPSULE ENDOSCOPY (VCE): Introduction, Evolution, Indications
byajayyadav753
 
High Resolution Manometry ccv 4.0 on Esophageal motility disorders.pptx
byajayyadav753
 
Gastrointestinal and hepatic disorders in pregnancy.pptx
byajayyadav753
 
Endoscopic Retrograde Cholangiopancreatography (ERCP): overview and technique...
byajayyadav753
 

Recently uploaded

PDF
HPM CLODINO SUPER (Clodinafop propargyl 15% WP)
byHpm India
 
PPTX
SONIA Trial Glucocorticoids for Community Acquired Pneumonia in Kenya
byArchitMehta11
 
PPTX
Craniopharyngioma: A Comprehensive Overview
byArchitMehta11
 
PPTX
from risk to resilience DEVELOPING EBP fall prevention protocole for geriatri...
byInassealarousi
 
PPTX
Cardiomyopathies; Hypertophic, Dilated cardiomyopathy, Broken heart syndrome.
byAjoke Onigbanjo
 
PDF
Venetoclax Tablets for Leukemia Treatment
byLetsMeds
 
PPTX
Chemistry of carbohydrates-II. Chemical properties, Monosaccharides, Disaccha...
byProf Viyatprajna Acharya
 
PDF
Physiology of the parturition and lactation
byMedicoseAcademics
 
PDF
female Reproductive Physiology before Pregnancy
byMedicoseAcademics
 
PPTX
THE BIOMECHANICS OF JOINT CLASSIFICATION.pptx
bydrnidhimnd
 
PDF
HPM GARUD (Glyphosate 41% SL) - Herbicides
byHpm India
 
PDF
Olaparib Tablet For breast and ovarian cancers
byLetsMeds
 
PPTX
POSITRON EMISSION TOMOGRAPHY ( PET SCAN)
bysakshinavale79
 
PPTX
menstrual cycle , amenorrhoea and dysmenorrhea.pdf.pptx
byAbdulghani Nasser Jaafar
 
PPTX
Management of posioning and drug overdose toxicity.pptx
byDebendra Suman
 
PDF
Conc Urine formation and related disorders
byMedicoseAcademics
 
PDF
Best Medical Billing Audit Companies_ Improve Accuracy & Boost Healthcare Rev...
byfexoi.com
 
PPTX
OBSESSIVE COMPULSIVE DISORDER(OCD) IN DETAIL.pptx
byDr.Prakashkumar More
 
PPTX
Anatomy of General Connective Tissue.pptx
byMathew Joseph
 
PPTX
Chemistry of carbohydrates-III polysaccharides, sugar derivatives
byProf Viyatprajna Acharya
 
HPM CLODINO SUPER (Clodinafop propargyl 15% WP)
byHpm India
 
SONIA Trial Glucocorticoids for Community Acquired Pneumonia in Kenya
byArchitMehta11
 
Craniopharyngioma: A Comprehensive Overview
byArchitMehta11
 
from risk to resilience DEVELOPING EBP fall prevention protocole for geriatri...
byInassealarousi
 
Cardiomyopathies; Hypertophic, Dilated cardiomyopathy, Broken heart syndrome.
byAjoke Onigbanjo
 
Venetoclax Tablets for Leukemia Treatment
byLetsMeds
 
Chemistry of carbohydrates-II. Chemical properties, Monosaccharides, Disaccha...
byProf Viyatprajna Acharya
 
Physiology of the parturition and lactation
byMedicoseAcademics
 
female Reproductive Physiology before Pregnancy
byMedicoseAcademics
 
THE BIOMECHANICS OF JOINT CLASSIFICATION.pptx
bydrnidhimnd
 
HPM GARUD (Glyphosate 41% SL) - Herbicides
byHpm India
 
Olaparib Tablet For breast and ovarian cancers
byLetsMeds
 
POSITRON EMISSION TOMOGRAPHY ( PET SCAN)
bysakshinavale79
 
menstrual cycle , amenorrhoea and dysmenorrhea.pdf.pptx
byAbdulghani Nasser Jaafar
 
Management of posioning and drug overdose toxicity.pptx
byDebendra Suman
 
Conc Urine formation and related disorders
byMedicoseAcademics
 
Best Medical Billing Audit Companies_ Improve Accuracy & Boost Healthcare Rev...
byfexoi.com
 
OBSESSIVE COMPULSIVE DISORDER(OCD) IN DETAIL.pptx
byDr.Prakashkumar More
 
Anatomy of General Connective Tissue.pptx
byMathew Joseph
 
Chemistry of carbohydrates-III polysaccharides, sugar derivatives
byProf Viyatprajna Acharya
 

Gastrointestinal and Hepatic manifestations of Systemic Diseases -II.pptx

  • 1.
    Gastrointestinal and Hepatic manifestationsof Systemic Diseases - II Dr. Ajay Kumar Yadav DM1 resident Gastroenterology 2080/11/30
  • 2.
    Layout • Gastrointestinal andhepatic manifestations of Red Blood Cell Dyscrasias Endocrine Diseases Renal Diseases Cardiac Diseases Pulmonary Diseases Critical Illness and Sepsis Neurological Diseases Infiltrative diseases Heavy Metal Toxicity Disorders of Lipid Metabolism
  • 3.
    Red Blood CellDyscrasias Sickle Cell Disease • AR abnormality of the β-globin chain of Hb  HbS polymerizes when deoxygenated  gelatinous network  stiffens the erythrocyte membrane and increases viscosity  micro-vascular occlusion  ischemia and infarction of the organs and RBC destruction • Splenic Involvement  First 6 months of life, splenic congestion and sickling  functional asplenia.  With repeated hemorrhages and infarctions occur spleen becomes smaller and is eventually replaced by fibrous tissue: autosplenectomy.  ↑susceptibility to infection with encapsulated bacteria  Radiologically, the spleen is small and often calcified
  • 4.
    • Acute splenicinfarction – more common in SC-HbC or SC thalassemia than in homozygous SCD – LUQ pain, N/V, splenic rub, occ. abscess, pseudocyst or rupture • Acute splenic sequestration – sudden pooling of blood in the spleen  rapid splenic enlargement and a drop in Hb. – In homozygous SCD, it occurs only in infants and children – In SC-thalassemia, can occur at any age
  • 5.
    Fig. CT showingSplenic sequestration Fig. Complications of SCD
  • 6.
    Biliary Tract Involvement •Cholelithiasis (70%) – Pigmented stones, chronic hemolysis, calcium bilirubinate, radiopaque • Choledocholithiasis (18 to 30%) • Sickle cholangiopathy – cholestatic jaundice w/o choledocholithiasis – d/t ischemic bile duct injury. Hepatic involvement • Acute sickle hepatic crisis – 10% of patients of painful crisis – stagnation of sickled cells in the hepatic sinusoids  decreased hepatic blood flow. – RUQ pain, N/V, tender hepatomegaly, low-grade fever, leukocytosis, and ↑AST/ALT(1-3×) and TB/DB • Acute hepatic sequestration – Lungs, spleen > liver – acute hepatic enlargement, rapid drop in Hct, ↑ reticulocyte count, and mild increase in liver enzymes and bilirubin
  • 7.
    • Acute sickleintrahepatic cholestasis – rare, potentially fatal complication caused by widespread sickling in the sinusoids  hypoxia and intra- canalicular cholestasis. – severe form of hepatic crisis with severe hyperbilirubinemia, coagulopathy, and renal insufficiency/failure ultimately resulting in liver failure. • Acute hepatic failure – rarely occurs, usually in the presence of CLD • VOD (39%) • Liver abscesses – secondarily infected hepatic infarct • Miscellaneous GI Problems  Abdominal pain  a/w vaso-occlusive crisis  a/w pain elsewhere, such as in the limbs and chest  typically relieved with hydration and oxygen within 48 hours.  d/t small infarcts of the mesentery and abdominal viscera  Acute pancreatitis: not common  d/t GB stones, ischemic injury  Duodenal ulcers  d/t reduced mucosal resistance  Ischemic bowel
  • 8.
    Hemosiderosis • With multipleBT and hemolysis in SCD • Pts with thalassemia: ↑BT requirement than SCD + ↑intestinal uptake of iron from ineffective erythropoiesis  more visceral iron loading. • On CT, the density of the liver and spleen increases with hemosiderosis. • On MRI, the magnetic signal diminishes in the liver as the iron concentration increases. – MRI T2 techniques correlate with hepatic iron content and can be used to guide therapy. • Ferritin is a poor measure of iron overload, because it is an APR • T/t: iron chelators: S/C deferoxamine, oral (deferiprone and deferasirox)
  • 9.
    Coagulation disorders • Intramuralhematomas – due to trauma or bleeding diatheses most commonly involve the duodenum (D2/3) or jejunum, respectively. • Von Willebrand Disease (VWD) – the most common inherited bleeding disorder – GI bleeding commonly occurs in a/w GI angioectasias or w/out visible lesions. • Heyde syndrome – calcific aortic valve stenosis + GI bleeding – acquired deficiency of VWF as the multimers are reduced in size from the shear stress. – AVR  corrects the abnormality – LVAD (30-40%)
  • 10.
  • 11.
    Fig. Pathophysiology ofacquired VWD in AS Fig. Calcified AS with GI angiectasias
  • 12.
    GI manifestations • Crampingpain abdomen, N/V, bloody diarrhea • Rarely, pancreatitis, hemoperitoneum, colonic perforation, or stricture
  • 13.
    ENDOCRINE DISEASES Diabetes Melitus Cancer • a/w ↑ risk of certain GI malignancies: Pancreatic cancer, HCC, CRC • The association may be due in part to shared risk factors such as aging, obesity, diet, and physical inactivity. • Metformin may reduce the risk of cancer, whereas insulin may increase it. • Insulin resistance  secondary hyperinsulinemia  ↓IGFBP ↑IGF-1  stimulate cancer growth. • modest increase in pancreatic cancer with DM > 5 years • Chronic pancreatitis with pancreatic insufficiency increases the risk of both DM and pancreatic cancer • Pancreatic adenocarcinoma should be considered in an older patient with new-onset, poorly controlled DM, especially with weight loss
  • 14.
    Metformin and cancer Huaet al. Journal of Translational Medicine (2023) 21:403 https://doi.org/10.1186/s12967-023-04263-8
  • 15.
    Hua et al.Journal of Translational Medicine (2023) 21:403 https://doi.org/ 10.1186/s12967- 023-04263-8
  • 16.
    Esophageal involvement • esophagealdysmotility (up to 50%), symptomatic only 25%. • Defects include decreased LES pressure, delayed transit, multi- peaked or spontaneous contractions, and reduced amplitude of contractions • Esophagitis (40%) • oral and esophageal candidiasis  dysphagia/odynophagia • predisposing factors: impaired immunity, esophageal stasis from dysmotility, and hyperglycemic impairment of neutrophil function and opsonization Gastric involvement • Gastroparesis • Type 1 DM  15% to 20% incidence of APCA, autoimmune atrophic gastritis (5% to 10%), and pernicious anemia (2.6% to 4%). • Autoimmune atrophic gastritis  IDA • ↑ risk for type I gastric carcinoids and probably gastric cancer. • association between DM and PUD: controversial – increases the risk of ulcer bleeding, perhaps secondary microangiopathy impair mucosal integrity. • no clear association between Hp and DM
  • 17.
  • 22.
    Complications of Gastroparesis • Dehydration •Malnutrition • Fluctuating blood sugar
  • 23.
    Small bowel involvement •Celiac disease: 4% (DM) Vs 0.5% (GP) – Predominant non-GI manifestations s/a short stature, pubertal delay, fat soluble vitamin deficiencies, anemia, osteoporosis, and/or reproductive disorders. • Type 1 DM with celiac disease – poor glycemic control, hypoglycemic episodes, and microvascular complications • Constipation > Diarrhea (up to 22%). • Diarrhea: often episodic, painless, and sometimes nocturnal, steatorrhea (uto 75%) • Metformin induced, even after years of t/t • Etiologies of diarrhea related to DM – drugs, fast transit, autonomic neuropathy, celiac disease, SBBO, excess use of sugar-free sweeteners, pancreatic insufficiency, and hormones • Neuropathy may cause diarrhea by altering fluid and electrolyte transport and by altering motility. • Treatment of diarrhea – t/t of specific etiology or loperamide. – Clonidine stimulates α2- adrenergic receptors but may worsen orthostatic hypotension. – Octreotide, or the long-acting octreotide analog lanreotide may help
  • 24.
    Colonic and analinvolvement • Constipation (>50%) – long-standing DM impaired gastrocolic reflex and delayed colonic transit. • Occasionally, megacolon and (rarely) intestinal pseudo- obstruction • Ischemic colitis • Fecal incontinence a/w dysfunction of the IAS and/or reduced sensitivity of the rectum to distension. GB involvement • Possible causes of GB dysfunction  defect in the cholinergic pathway,  reduced α-adrenergic tone,  deficiency of CCK receptors,  arteriolar disease impairing muscle contraction,  hyperglycemia, and hyperinsulinemia. • Risk of GB stones: controversial, common risk factors • Emphysematous cholecystitis  Peculiar with DM  probably due to ischemia of the GB from vascular compromise, with proliferation of gas-forming organisms.
  • 25.
    Fig. Emphysematous Cholecystitis.CT abdomen shows gas within the wall of the gallbladder (horizontal arrow) as well as within the lumen of the gallbladder (vertical arrow). Fig. Emphysematous cholecystitis. X-ray abdomen erect shows gas within lumen (arrow) as well as within wall of GB (arrowhead)
  • 26.
    Pancreatic involvement • DM pancreatic insufficiency d/t vasculopathy + autonomic neuropathy with impaired enteropancreatic reflexes. • T1DM: autoimmune processdamage both endocrine β cells and adjacent exocrine cells + low insulin level reduced trophic effects on acinar cells. • CP, Pancreatic cancer, hemochromatosis, AP, partial pancratectomy  T3cDM – ↑hypoglycemic episodes, rare DKA • ↑ed incidence of AP, a risk that is reduced by taking antidiabetic drugs. • AP can complicate DKA in 11% of cases; transient hypertriglyceridemia is thought to be a contributing factor. – may worsen volume depletion and hyperglycemia a/w DKA. • DKA itself can be a/w abdominal pain and mild elevations of amylase and lipase without pancreatic inflammatory changes
  • 27.
    Hepatic involvement • AbnormalLFT common in T2DM, esp. serum ALT. – If ALT < 3 UNL and no cause found, oral antidiabetic and statins can be started • Hepatitis or ALF has been a/w thiazolidinediones, and cholestasis with sulfonylureas. – Metformin has not been a/w hepatotoxicity. • MASLD common in DM, is a manifestation of insulin resistance, often found in conjunction with the metabolic syndrome. • DM has been shown to ↑ the risk of ALF independent of underlying liver d/s • Cross-sectional and longitudinal studies: HCV ↑ risk of T2DM(OR 1.6 to 2.1) – Similarly, HCV is a strong predictor of new-onset DM after LT – HCV eradication improves insulin sensitivity and reduces the incidence of DM.
  • 28.
    Fig. New nomenclatureof NAFLD by AASLD
  • 29.
    Hepatogenous diabetes • 30%to 60% of cirrhotic patients • characterized by insulin resistance in muscular, hepatic, and adipose tissues, as well as hyperinsulinemia and an impaired response of pancreatic islet cells. • reduced frequency of micro- and macroangiopathic complications, perhaps d/t lower BMI, lipids, and BP compared to T2DM. • ↑risk for hypoglycemia due to minimal glycogen storage in the liver, impaired hepatic insulin extraction, high catabolic rate, and sometimes superimposed alcoholism. • Should generally have no dietary restrictions, because they are often malnourished. • Oral hypoglycemic drugs are metabolized by the liver, so may lead to hypoglycemia. – Although metformin reduce insulin resistance, it is relatively contraindicated d/t risk of lactic acidosis in cirrhotic patients who drink alcohol. • LT cures DM in 67% of cirrhotic-diabetic patients.
  • 30.
    Fig. Pathophysiology ofHepatogenous diabetes in cirrhotic liver
  • 32.
    Thyroid Disease Hyperthyrodism • Clinicalmanifestations: apathetic thyrotoxicosis  thyroid storm • GI symptoms: abdominal pain, N/V, LOW, and diarrhea. • may be a/w other autoimmune diseases s/a pernicious anemia, celiac disease, and UC. • Dysphagia: rare – direct compression from a goiter or nodule, – Excess hormone  myopathy affect striated muscles of pharynx and upper 1/3rd esophagus, – increased esophageal contraction velocity. • Gastric emptying: normal, rapid, or delayed • Diarrhea (up to 25% of pts) – Accelerated transit time + dietary fat hyperphagia  steatorrhea
  • 33.
    • Diarrhea maydecrease with propranolol, suggesting improvement of a relative adrenergic stimulatory state • Mild abnormalities in serum aminotransferases or ALP, clinically significant abnormalities rare – d/t thyroid dysfunction itself, or drug therapy (PTU), or concomitant (AIH and PBC) • Severe cholestatic hepatitis, jaundice, and/or ALF: rare – d/t mismatch between increased hepatic oxygen consumption and hepatic blood flow. – Predominant zone 3 hepatic necrosis with or without concomitant RHF typical.  t/t: Anti-thyroxine + emergent thyroidectomy and/or LT
  • 34.
    Hypothyrodism • most commonlyd/t Hashimoto’s thyroiditis or to thyroid ablation for hyperthyroidism. • a/w UC, pernicious anemia, DM, celiac disease, and PBC. • Cl/f: constipation, anorexia, N/V, and abdominal pain. • Esophageal manifestations: dysphagia and reflux, d/t motility disorder with low LES pressure and reduced amplitude of contractions. • Gastric manifestations: reduced acid secretion or delayed gastric emptying, phytobezoars • Small/large bowel manifestations – SBBO – SI transit time may be normal or delayed – Colonic hypomotility  obstipation, ileus, megacolon, or volvulus. • Pathology: neuropathy or accumulation of GAGs in the interstitial tissues. • Ascites in myxedema: – high protein (>2.5 g/dL) with a variable SAAG, and a low TLC with a predominance of lymphocytes. – Resolution occurs with thyroid replacement, not with diuretics.
  • 35.
    Medullary Carcinoma ofthe Thyroid (MTC) • calcitonin-producing tumor of the C cells of the thyroid gland. • Sporadic (80%) or Familial (20%, MEN-II). • Diarrhea: 1/3rd patients, particularly in those with extensive mets • ↑calcitonin,PGs, 6-HIAA, or histamine Fig. MTC. Notice the bands of amyloid (thick arrow) interspersed between nests of tumor cells
  • 36.
    Parathyroid Disease Hyperparathyrodism • GIcomplaints: constipation (large bowel atony), N/V (gastric atony), anorexia, and weight loss. • Abdominal pain d/t: PUD, pancreatitis, or atony. • Gastric acid hypersecretion and/or hypergastrinemia have been found in some but not other studies. • Constipation may be due to a reduction in neuromuscular excitability by high calcium levels • Incidence of AP: 1% to 12%; Pancreatic calculi, mainly intraductal: 80% – T/t: Parathyroidectomy
  • 37.
    Hypoparathyrodism • The mainGI manifestation is steatorrhea. – d/t insufficient CCK release and pancreatic enzyme secretion. • Replacement of dietary LCTG with MCTG  reduces fecal fat losses fecal calcium losses from saponification • Occ. a/w celiac disease – Underlying celiac disease s/b suspected even in the absence of diarrhea in a hypoparathyroid pt whose serum calcium levels do not respond to t/t. • May cause a low serum ALP but zinc deficiency, magnesium deficiency s/b considered as well.
  • 38.
    Adrenal Disease Addison’s Disease(AD) • GI symptoms (>50% ): N/V, diarrhea, and pain abdomen • A/w celiac disease (8% to 12%) - similar HLA associations. • Poor absorption of glucocorticoids d/t associated celiac disease may complicate the therapy of AD whereas glucocorticoid t/t may mitigate celiac sprue. • Atrophic gastritis and pernicious anemia may also be present. • ↑ serum aminotransferases resolve on glucocorticoid replacement therapy. Pheochromocytoma • GI manifestations: N/V, abdominal pain and, less commonly, constipation, ileus, megacolon, ischemic colitis, and perforation. • Catecholamines  decrease intestinal motility and tone by relaxation of intestinal smooth muscle + ischemia from vasoconstriction of splanchnic arterioles. • The effects can be relieved by α- adrenergic blockers - phentolamine. • Hypertensive emergencies can occur with the use of opioids and other medications (as during endoscopic procedures).
  • 39.
    Pituitary Disease • Thehypothalamic-pituitary-adrenal axis provides an important link between the brain and the gut (Brain-gut axis) • Pituitary disorders infrequently affect the GI tract, except in a/w MEN-I syndrome. • Hypercortisolism ↑increased incidence of GU with concomitant NSAIDs • Acromegaly a/w – increased length and circumference of the colon and slow colon transit time  standard bowel preparation often inadequate. – ↑risk of CRC, colonic polyps, and other GI tract cancers. • ↑ GH and IGF-1  epithelial cell proliferation • Octreotide t/t ↑GB stone formation – Symptomatic gallstone disease may occur following withdrawal of octreotide.
  • 40.
    Renal Diseases • Anorexia,N/V, abdominal pain, and constipation are common – N/V: d/t DDS, uremic toxins, hypotension, and rapid changes in osmolality. – GER occurs, particularly in those undergoing PD • Gastric dysfunction may be a/w impaired gastric myoelectric activity, increased levels of GI hormones (e.g., CCK, gastrin) that modulate GI motility, uremic toxins, DM, autonomic nerve dysfunction, and the physical restriction caused by PD • Gastroduodenal lesions—usually inflammation, erythema, and erosions—are common • Prevalence of Hp infection: normal or reduced • Occult and overt GI bleeding: common – d/t uremia, platelet dysfunction and antiplatelet agents, NSAIDs, and/or heparinization during HD – ↑prevalence of angiectasias in the upper or lower GI tract
  • 41.
    • Acute mesentericischemia – non-occlusive, may be d/t episodes of hemodynamic instability during HD. – Rt > Lt sided colon or multiple areas – poor prognosis. – Risk factors: NSAID use and aggressive EPO administration. • Constipation and fecal impaction: HD > PD – Constipation: inactivity, dehydration, reduced fiber intake, metabolic abnormalities, phosphate binders, aluminum antacids, ion exchange resins, comorbidities, and prolonged colonic transit – Diarrhea: SBBO from small bowel dysmotility, abnormal bile acid metabolism, exocrine pancreatic insufficiency, or amyloidosis • Oral sodium phosphate used as a bowel preparation  phosphate nephropathy, hyperphosphatemia, hypocalcemia, hypokalemia, and/or hyper- or hyponatremia • Is PEG safe in CKD? – PEG is an isosmotic solution that passes through the bowel without absorption or secretion. – Studies have shown that PEG is safe in patients with CKD
  • 42.
    • GI necrosismay occur with sodium polystyrene sulfonate (Kayexalate), commonly used to treat hyperkalemia, in combination with sorbitol to prevent constipation. • Aluminum-containing antacids or sucralfate  aluminum toxicity or fecal concretions  obstruction and/or perforation. • Pts on HD ↑risk of perforation during colonoscopy, d/t deposition of β2-microglobulin ≈GI amyloidosis • Peritonitis related to the dialysis catheter in pts on PD is most commonly caused by a single organism and usually resolves with appropriate antibiotics. – Non-resolving peritonitis: polymicrobial pathogens + increase in effluent amylase concentration suggest bowel perforation, delayed diagnosis  ↑mortality • Sclerosing peritonitis – rare and lethal condition in PD – characterized by peritoneal thickening that encapsulates the bowel, causing obstruction. – CT abdomen: peritoneal thickening and calcification, loculated fluid collections, and adherent small bowel loops
  • 43.
    • Hernias: commonin pts on PD, esp. at the catheter insertion site, inguinal canal, umbilicus, and sites of previous surgeries. • Whether the incidence of acute pancreatitis is increased HD is controversial. • Macro-amylesemia Fig. CT showed diffuse parietal and visceral peritoneal calcifications encasing the small-bowel loops (arrows), consistent with encapsulating peritoneal sclerosis.
  • 44.
    Pulmonary Diseases Bronchial Asthma •GERD: 3/4th of pts – worsened by the use of asthma medications (theophylline, β‐ agonists)↓LES • Worsened wheezing: reflex bronchial constriction > aspiration of gastric contents • Chronic idiopathic cough is commonly a/w GERD • Even in the absence of heartburn, acid may trigger nocturnal cough or laryngospasm COPD • a/w PUD • risk for GU appears to increase with the number of cigarettes smoked per day. • ↑ed mortality a/w perforated or bleeding ulcers, especially with use of glucocorticoids
  • 45.
    α 1 Antitrypsindeficiency ‐ ‐ • autosomal co-dominant disease • GI manifestations: CLD, cirrhosis, and HCC
  • 46.
    Cystic fibrosis • mostcommon genetic illness among Caucasians, with an incidence of about 1 per 2500 • Mutations in CFTR on chromosome 7q defect in mucosal cAMP ion and water transport • GI manifestations: distal intestinal obstruction (adults), meconium ileus (infants) • Gastroesophageal reflux may enhance the pulmonary symptoms – Contributing factors: ↓LES tone + ↓saliva production + GI hypomotility + chronic cough • Pancreatic insufficiency • Protein–calorie malnutrition • Prolonged pancreatic enzyme supplementation  fibrosing colonopathy – bloody diarrhea a/w diffuse narrowing of the colon (mostly the right colon) with rectal sparing • Clinically apparent liver disease usually develops during or before puberty with a prevalence of 13–17%. • Focal biliary cirrhosis progressive portal hypertension (10%) • ↑GI mallignacies + non-GI cancers, including kidney, thyroid, endometrial, lymphoma, NMSCC
  • 47.
    Critical illness andSepsis • Frequent upper GI dysmotility  high gastric residual volumes, abdominal distension, N/V, regurgitation, and aspiration. • Bacterial colonization of the upper airways (may originate from flora in stagnant gastric contents) pneumonia • Low to absent LES pressure +↓ esophageal contractions + diminished saliva + frequent straining (usually coughing from ET suctioning)  reflux and aspiration. • Acute stress-induced gastropathy: common, with hemorrhage ↑ed in pts on MV and those with significant coagulopathies. • Constipation (no bowel movement in the first 96 hours in the ICU): 50% – main risk factors: opioid intake and disease severity. – Fiber laxatives s/b used with caution  fecal impaction (if fluid intake inadequate). • Ischemic colitis: following hypotensive episodes. • Acalculous cholecystitis: manifests as acute abdominal pain, unexplained leukocytosis, or abdominal sepsis.
  • 48.
    Fig. Pathogenesis ofacute stress-ulcer
  • 50.
    • Hepatic involvementin sepsis is the most common cause of jaundice in ICU patients. – Phase 1: hepatic hypoperfusion ↓ synthetic function of the liver – Phase 2: liver response to sepsis as the major protective organ. • Pts with cirrhosis: ↑hospitalizations a/w sepsis and an ↑ed likelihood of death from sepsis. • LFT abnormalities: – Peak TB/DB: usually 5- 10 mg/dL – SALP: ↑ed in 50% pts; rarely ≥ 2 to 3 times UNL – Serum aminotransferases: usually normal but can be slightly elevated. – Serum albumin: may be low but no lower than in non-jaundiced sepsis. • Bile duct injury from sepsis and trauma  progressive sclerosing cholangitis, usually small duct disease. – s/b considered with persistent hyperbilirubinemia and elevated serum ALP levels after resolution of the sepsis • No specific treatment for hepatic involvement in sepsis indicated. • Prognosis is unrelated to hepatic involvement or to the height of the hyperbilirubinemia in pts with sepsis, but rather to the underlying process.
  • 52.
    Cardiovascular Diseases • Cardiacdiseases affecting liver  congestive hepatopathy, ischemic hepatopathy, or even cardiac cirrhosis with ascites. • Liver diseases affecting lungs and heart  HPS, PPH, pericardial effusions CCM, and high-output failure • Diseases affecting both the liver and the heart/circulation include sepsis and infiltrative disorders s/a hemochromatosis, amyloidosis, and sarcoidosis. • Heart disease (HF, CCP, cor pulmonale)  intestinal malabsorption/PLGE. • Ischemic heart disease  risk factor for ischemic colitis • Symptomatic GI angiectasias may occur in pts with AS (Heyde syndrome) and 30%-40% after LVAD
  • 54.
    NEUROLOGIC DISEASES Abdominal epilepsy •rare condition, children > adults. • characterized by 1) paroxysmal GI complaints, usually abdominal pain, N/V of unclear etiology; 2) symptoms of a CNS disturbance, usually lethargy and confusion; 3) abnormal EEG indicating a seizure disorder; and 4) sustained improvement with AED  Temporal lobe involvement • Head trauma  stress gastropathy and delayed gastric emptying • Stroke – pharyngeal dysphagia (brainstem lesion) – stress gastropathy – Constipation: d/t prolonged colonic transit time, immobility, and altered diets
  • 55.
    Diseases of theCNS Abdominal migraine • children (1-4%) > adults, F>M T/t: 1. Non-pharmacologic therapy: removal of triggers 2. Antimigraine therapies may be successful
  • 56.
    Multiple sclerosis (MS) •most frequent chronic neurologic disease in young persons in developed countries. • GI disturbance: 40% of MS pts – constipation and fecal incontinence – early satiety, N/V , – postprandial discomfort a/w delayed gastric emptying. • ↑prevalence of celiac disease • Constipation: a/w – prolonged colonic transit time, – pelvic floor dysfunction, – reduced colonic compliance, – immobility, – paradoxical anal contractions, – absence of postprandial colonic motor – medications (anti-cholinergics, opiates) • Defecography: – pelvic outlet obstruction with failure of the puborectalis and anal sphincter muscles to relax • Fecal incontinence in MS – d/t reduced EAS tone, reduced anorectal sensation, and spontaneous rectal contractions.
  • 57.
    Spinal Cord Injury(SCI) • Usually present with constipation, abdominal pain, distension, bowel accidents, and autonomic hyper-reflexia • Spinal shock occurs for several weeks after the injury – all autonomic and reflex activities are lost below the level of injury. • Abdomen: distended and flaccid, with no sensation below the level of injury and with absent or hypoactive bowel sounds d/t gastric dilatation and a paralytic ileus. – Incidence of PUD and hemorrhage: ↑ed. • Spinal shock ends  return and then exaggeration of autonomic reflex activity below the level of injury. • SCI lies above T6  autonomic hyperreflexia  intense reflex vasoconstriction of splanchnic blood flow  hypertension, diaphoresis, bladder spasms, and diarrhea.
  • 59.
    • The diagnosisof an acute abdomen may be delayed in a high-level SCI • Abdominal operations are challenged by deformities or spasticity. • Hyper-reflexic HTN, ↓pulmonary excursion, prolonged ileus, and chronic septic foci: ↑risk of wound infections. • ↑GER: supine position, ↑ IAP d/t constipation • Gastric emptying: either delayed or normal – Promotility agents effective (intact ENS) • Fecal impaction/constipation (esp with SCI above T7) < Fecal incontinence, megacolon, stercoral ulcers, and hemorrhoids • First 6 months after SCI: biliary sludge > GB stones, > 6 months, the prevalence of GB stones is high (17% to 31% of SCI patients)
  • 60.
    SMA syndrome (Wilkie’ssyndrome, cast syndrome) • D3 is intermittently compressed by the overlying SMA • May occur following rapid weight loss, prolonged supine positioning, and the use of spinal orthoses. • Intermittent or PP epigastric pain f/b billious volmiting  pain relieved by prone, knee-chest, left lateral position or Hayes maneuver
  • 62.
    Extrapyramidal (Movement) Disorders •Hypokinetic (PD) and Hyperkinetic (HD) • Lewy bodies, the pathognomonic feature of PD, are found in the ENS of the esophagus, stomach, and colon. • Dopaminergic deficiency in the ENS and involvement of the DMN of vagus ↓ parasympathetic innervation to much of the GI tract • In PD, saliva is excessive, from reduced effectiveness of swallowing. • All stages of swallowing—oral, pharyngeal, or esophageal—may be affected by PD • Delayed gastric emptying, particularly of solids  Gastroparesis may interfere with levodopa  Metoclopramide is C/I: aggravates PD by blocking central dopamine receptors, Dopamine - safe
  • 63.
    • Gastritis causedby Hp may interfere with levodopa absorption; an improved response to levodopa occurs after its eradication. • Constipation: Frequent, even before PD  Medications + reduced mobility + weak abdominal straining  Prolonged orocecal transit time + dys-synergia d/t dystonia (may prevent the EAS from relaxing)  T/t: BOTOX, Apo-morphine • Rarely, megacolon, pseudo-obstruction, volvulus, or even perforation • Huntington disease (HD)  AD neurodegenerative disease characterized by involuntary movements, psychiatric disturbance, and cognitive decline.  Dysphagia in HD occurs in the preparatory oral phase (postural instability, tachyphagia, poor lingual control), the oral phase, the pharyngeal phase, or esophageal phase.
  • 64.
    GI symptoms seenin 85% of pts of autonomic dysfunction/diseases
  • 65.
    Disease of theNMJ Myasthenia gravis: • Characterised by fatiguable muscle weakness. • Dysphagia and aspiration: common Pharynx and upper 1/3rd esophagus involved. Classically, contractions weaken with repetitive swallows • may be a/w other autoimmune diseases such as pernicious anemia, AIH, or PBC. Muscular Dystrophy • DMD – mutation of the dystrophin gene  abnormal dystrophin (skeletal muscle > smooth muscle, myenteric neurons) • Myotonic MD: Most of the GI tract involved • Oropharyngeal symptoms: typical, may lead to aspiration • Delayed gastric emptying + reduced postprandial ↑ in motilin levels  Early satiety, N/V, epigastric pain, and/or bezoars. • Episodic severe diarrhea, malabsorption, and fecal incontinence
  • 66.
    INFILTRATIVE DISEASES Amyloidosis • groupof infiltrative disorders that result from the extracellular deposit of amyloid fibrils
  • 67.
  • 68.
    Oral, Esophageal, andGastric Involvement • Macroglossia: pathognomonic  dry, fissured, ulcerated, and indented by teeth  airway obstruction, speech difficulties, oral dysphagia, and malocclusion of teeth. • Esophagus: 13% (radiologic study) and 22% (autopsy)  dysphagia, chest pain, heartburn, and hematemesis.  Basal LES pressure: normal or low, amplitudes of esophageal contractions: ↓ed • Involvement of the submandibular gland  xerostomia • Gastric involvement : 12% (autopsy) and 8% (endoscopy)  Only 1% symptomatic: Early satiety, N/V, abdominal pain, or hematemesis.  GOO  Gastroparesis, esp. with familial amyloidotic polyneuropathy  Loss of rugal folds and decreased motility when smooth muscle is replaced by amyloid.  EGD: granular appearance, friability, polyps, erosions/ulcers, and enlarged folds
  • 69.
    Small and LargeBowel Involvement Small Bowel (most involved):  diarrhea, steatorrhea, PLGE, hemorrhage, obstruction, ischemia and infarction, pneumatosis cystoides intestinalis, intussusception, constipation, pseudoobstruction, mesenteric infiltration, and perforation  Thickened folds (d/t amyloid in the vasculature)  ischemic enteritis, amyloid in the wall, or hypoalbuminemia.  Hypoalbuminemia results from malabsorption, PLGE, and/or nephrotic syndrome Large bowel involvement  May mimic IBD, malignancy, or ischemic colitis.  Diarrhea may be d/t autonomic dysfunction, delayed, SBBO, bile acid malabsorption, pancreatic insufficiency  Steatorrhea: common in FAP but not AL amyloidosis.  Hemorrhage d/t: direct vascular and tissue infiltration ↑ed friability or ischemia + impaired vasoconstriction.  Prolonged PT: d/t liver dysfunction, malabsorption, ↓vitamin K intake, or ↓FX.  Amyloidosis occurs clinically in 0.9% of pts with CD and in 0.07% of pts with UC
  • 70.
    Hepatic Involvement • Hepaticamyloidosis has no clinical significance, except in FAP • When symptomatic: weight loss, fatigue, abdominal discomfort, and anorexia. • Ascites is more often due to cardiac failure than to liver disease. • Stigmata of CLD: uncommon. – Splenomegaly is usually a/w hepatomegaly – Hyperbilirubinemia is a/w poor prognosis.
  • 71.
    Granulomatous Liver Disease •MCC  Developed world: PBC  Developing world: TB • Clinical manifestations of hepatic granulomas  asymptomatic > symptomatic (hepatomegaly, RUQ pain, fever, and/or weight loss) Sarcoidosis • multisystem granulomatous disorder of unknown cause. • ↑ed incidence and mortality in African Americans > Caucasians. • constitutional symptoms, lung disease, adenopathy, uveitis, proximal myopathy, lupus pernio, CN palsies, EN, hypercalcemia, and granulomas in many organs
  • 72.
  • 73.
    Gastrointestinal Involvement (rare) • Esophagus:rarely involved  Dysphagia or reflux.  Mucosal involvement: aphthous lesions, plaques, or nodules.  NM involvement: dysmotility in the cricopharynx or achalasia-like picture responding to glucocorticoids • Stomach: m/c GI site involved  usually asymptomatic > N/V, early satiety, abdominal pain. • Duodenal involvement from sarcoidosis is rare. • Ascites is rare and usually due to RHF or PHTN. – However, peritoneal studding with small nodules may cause a lymphocytic ascites • There may be an association between celiac disease and sarcoidosis ≈ both linked to HLA-DQ2 and HLA-DR3 • Pancreatic sarcoidosis: quite rare  Presentation: enlarged pancreas, biliary obstruction, abdominal pain, AP, or pancreatic insufficiency • Acute cholecystitis:  secondary to extrinsic compression of the cystic duct by lymph nodes or by granulomatous inflammation of the GB. • Obstructive jaundice:  granulomatous involvement of the bile ducts or surrounding lymph nodes.
  • 74.
    Sarcoidosis VS Crohn’sDisease (CD)  Distinguishing features suggesting Sarcoidosis: rare Schaumann bodies, granulomas outside the GI tract, and a dramatic response to glucocorticoids.  Fistulas, architectural distortion, and acute inflammation: uncommon Sarcoidosis Vs Lymphoma • Unlike lymphoma, abdominal adenopathy in sarcoidosis is characterized by lymph nodes that are generally < 2 cm in diameter, discrete (rather than confluent), and spare the retro-crural area.
  • 75.
    Hepatic and SplenicInvolvement • Hepatic involvement: asymptomatic > pain abdomen (m/c) > jaundice (rare) • Jaundice is d/t intrahepatic cholestasis, hemolysis, hepatocellular dysfunction, or obstruction of the EHBD by enlarged lymph nodes. • Cholestasis may be d/t sarcoidosis of EHBDs, bile duct compression by enlarged perihilar lymph nodes, involvement of the pancreas, or associated PBC and PSC. • Unlike PBC and PSC, pts with sarcoidosis usually have normal serum IgM levels, negative AMA, and negative ANCA. – In addition, they may have rapid improvement with glucocorticoids not seen with PBC or PSC. • Because cirrhosis is rare and liver function is usually preserved, encephalopathy and liver failure are unusual. • Splenic involvement: asymptomatic > LUQ abdominal pain, constitutional symptoms, hypersplenism, and rarely rupture.
  • 77.
  • 78.
    Lead Poisoning • s/bconsidered in pts with abdominal complaints and a history of occupational or environmental exposure, s/a ingestion or removal of lead‐ based paints, manufacture of batteries or jewelry, welding • Common symptoms include recurrent severe abdominal pain (lead colic), oral ulcers, constipation, stocking–glove paresthesias, psychiatric symptoms, and a metallic taste in the mouth.
  • 79.
    DISORDERS OF LIPIDMETABOLISM Hypertriglyceridemia • TG > 1000 mg/dl  acute and recurrent pancreatitis but rarely CP • Usually the pt has a familial hyperlipoproteinemia (Type IV) along with secondary factor, s/a poorly controlled DM, alcohol intake, or use of medications s/a estrogen. • The serum amylase level may be normal or minimally elevated Fabry disease • X-linked deficiency of α-galactosidase A • GI symptoms: abdominal pain and diarrhea (50% to 60%) • may be confused with IBS-D • Gastroparesis, N/V, autonomic neuropathy, bowel dilatation, formation of diverticula, reduced peristalsis, and SBBO
  • 80.
    Gaucher disease • deficiencyof glucocerebrosidase • characteristic Gaucher cells: macrophages engorged with lipid with a crumpled tissue paper appearance • Hepatosplenomegaly: common. • Hepatocytes are spared  liver failure is uncommon. • Portal hypertension: uncommon, d/t splenic enlargement and/or to intrahepatic obstruction from extensive deposits of Gaucher cells Niemann-Pick disease type B • deficiency of acid sphingomyelinase • characterized by accumulation of sphingomyelin within lysosomes, mainly in monocytes/macrophages. • Portal hypertension, liver failure, and cirrhosis are uncommon Fig. Gaucher cells with crumpled tissue appearance
  • 81.
    Tangier disease • ARdisorder characterized by accumulation of cholesterol esters in macrophages in tonsils, thymus, lymph nodes, marrow, liver, and the gut. • Mutation in the ATP-binding cassette protein (ABCA1)  mediates the efflux of excess cellullar sterol to apolipoprotein A-I  HDL. • The striking clinical findings include yellow-orange “streaked” tonsils (80% ), hepatosplenomegaly, and peripheral neuropathy. • Diarrhea w/out steatorrhea. Colonoscopy: orange-brown mucosal spots throughout the colon and rectum,
  • 82.
  • 83.
    References • Sleisenger andFordtran’s Gastrointestinal and Liver Disease 11th Edition • Yamada’s Textbook of Gastroenterology 7th Edition

Editor's Notes

  • #4 Acute splenic infarction is more common in SC-HbC or SC thalassemia than in homozygous SCD, owing to the combination of splenomegaly with near-normal Hb levels and relatively high blood viscosity
  • #9 D2 and D3 - vulnerable to damage from trauma. They are fixed between the anterior abdominal wall and the vertebral column, so they may be either compressed or torn away from the more mobile area
  • #16 Autoimmune atrophic gastritis can lead to iron deficiency anemia (due to hypochlorhydric iron malabsorption
  • #24 Ischemic colitis: d/t capillary basement membrane thickening and luminal narrowing of sub-mucosal arterioles in the colon.
  • #27 If ALT < 3 UNL and no cause found, oral antidiabetic and statins can be started; these regimens often decrease serum ALT levels as tighter blood glucose levels are achieved
  • #36 calcium can promote conversion of trypsinogen to trypsin, resulting in damage to acinar cells
  • #39 Octreotide t/t ↑GB stone formation, probably owing to suppression of CCK release and GB emptying.
  • #41 reduced fiber intake (d/t potassium-restricted diets)
  • #59 The diagnosis of an acute abdomen may be delayed in a high-level SCI, raising the mortality rate, because rigidity and rebound tenderness may be absent The ability to increase intra-abdominal pressure is lost in SCI above T7, promoting constipation. When spinal reflexes are lost, there is more incontinence and less constipation. The external anal sphincter does not contract with increased intra-abdominal pressure or with rectal distension.
  • #60 Hayes maneuver: pressure is applied below the umbilicus in cephalad and dorsal directions - elevates the root of small-bowel mesentery and may also relieve obstruction temporarily.
  • #69 pancreatic insufficiency from ischemia of acinar tissue by amyloid deposition in vessels
  • #70 Hepatic amyloidosis has no clinical significance, except in FAP, where the liver is the main organ involved.