ÁLTALÁNOS ORVOSTUDOMÁNYI KARI. sz. Belgyógyászati Klinika

Dr. Ferenc SZALAY professor emeritus

Semmelweis University

Clinic for Internal Medicine and Oncology

Differential diagnosis in

gastroenterology

Lecture for English course medical students 2020.04.22.

Not own figures have been imported

from open databases via internet,

from public guidelines of international

societies.

DECLARATION

GI bleeding

Upper GI (UGIB) - Lower GI - Obscure

Altered bowel movement – Diarrhea, Constipation

Jaundice –

Liver diseases

Biliary diseases: Stone, PBC,PSC, Tumors

Abdominal pain – GI related and non GI related

Pancreatic diseases

Pancreatitis – acute and chronic

P. tumor

IBD: Ulcerative colitis (UC) - Crohn D (CD).

IBS – irritable bowel syndrome

Topics to be discussed

Good history taking

= half diagnosis

Don’t forget

Importance of physical investigation

Upper GI tract bleeding (proximal to the ligament of Treitz)

Hematemesis bright red blood

coffee grounds

Melaena black, terry stool, >100ml, >12 h

Lower GI bleeding (distal to the ligament of Treitz)

Melaena

Hematochezia bright red or maroon colored

Obscure bleedingSymptomst of iron deficiency

Combination

GI BLEEDING

Václav (Wenzel)Treitz

1819 – 1872

Ligament of Treitzsuspensory muscle

Superior mesenteric vein Superior mesenteric artery

The problem with GI bleeding

Mortality – up to 10-14% (US, UK)

despite modern diagnostic and threapeutic technics

Male:female= 2:1

Asymptomatic – mild – severe

Can be life threatening emergency situation

MASSIVE GI BLEEDING

Clinically significant bleeding

Most critical the first 48-72 hours

P > 100/min

systolic RR < 100 Hgmm

postural RR > 20 Hgmm

> 2U transfusion demand /24 h

Ulcer disease

Esophagitis

Esophagogastric Varices

Vascular lesions

Neoplasms

Diverticula

Hemorrhoids

Fissures

IBD

Infectious colitis

GI BLEEDING etiology

UGIB

LGIB

Obscure GIB

Tools for diagnosis

Clinical symptoms – iron deficiency

Endoscopy – upper, lower

push enteroscopy

Izotope scintigraphy

Angiography

Capsula endoscopy

CT Angiography

MRI?

Surgical exploration

5-10% of GIB

Angiography for GI bleeding

Main goals:

1.Confirm the diagnosis of bleeding

2.Localize the bleeding site

3.Provide transcatheter therapy as needed

Very specific (100% for both UGIB and LGIB)

Very sensitive (90% for UGIB, 86% for LGIB)

Successful if bleeding is greater than 0.5 mL/min

Angiographic

signs of bleeding

Extravasation of contrast into the

lumen of bowel

Patients must be bleeding

quite briskly

Indirect signs of bleeding

Extravasation outside of the

vessels

Pseudoaneurism

AV fistula

Hyperemia

Neovascularity

The goals of management of GI bleeding

in order of priority

1. Correct hypovolemia

(hemodynamic resuscitation)

2. Arrest hemorrhage by the least

invasive means

3.Prevent recurrent hemorrhage

ABDOMINAL PAIN

GI Tract related

Not GI related

>1018 medical

conditions

can cause abdominal pain

Which in the given case?

ABDOMINAL PAIN.

Interviewing / physical invest.

8questions

ABDOMINAL PAIN. Interviewing/physical invest.

Localization where?

Time when? duration? frequency?

Oneset suddenly? gradually?

Intensity how severe?

Character aching? burning? gnawing? colicky?

Radiation no or yes? travel anywhere?

Aggravating or meals? antacids? alcohol? defecation?

alleviating circumstances medications(aspirin)? body position?

urination? menstruation?

Associated symptoms fever? chills?

Sudden acute

Recurrent chronic

ONSET OF ABDOMINAL PAIN

BEDSIDE DIAGNOSTIC TESTS FOR ABDOMINAL PAIN

General appearance

Is there shock?

Palpate the abdomen gently

Exemine for hernia

Listen to the bowel sounds

Rectal digital investigation

ACUTE ABDOMEN

Severe

Persistent

Sudden onset

Surgical intervention to treat (non surgical!)

Frequently associated with

nausea, vomiting, abd. distension,

fever, shock

CAUSES of ACUTE ABDOMEN

Trauma – blunt, perforating

Inflammation – appendicitis, cholecystitis, pancreatitis, pelvic,

Mechanical – small or large intestine, hernias,

Vascular – occlusive, aneurisma rupture

Perforation – any of above can end here

Tumor - intraabdominal bleeding

Non surgical causes

Surgical acute abdomen

When to operate?

Before sunset

or

Before sunrise

Non Surgical Causes

• Myocardial infarction (MI), Acute pericarditis

• PN, pulmonary infarction

• GE reflux, hepatitis

• Diabetic ketoacidosis (DKA )

• Acute Adrenal Insufficiency

• Acute Porphyria

• Rectus muscle hematoma

• Pyelonephritis, Acute salpingitis

• Sickle cell crisis

Clinical Diagnosis

ORIGIN OF ABDOMINAL PAIN

GI organs – OE, stomach, bowel, bile system, liver, pancreas

Kidney – urinary tract

Gynecological and obstetrics

Prostate

Blood vessels – artery, vein

Metabolic crisis (diabetes, porphyria, hypadrenia, C1 inhibitor def.)

Skin – herpes zooster

Hernia

Abdominal wall – muscle, shingle

Connective tissue

Poisoning – black widow spider bite, narcotic withdrawal

Functional and psychiatric causes- IBS

Referred pain – heart, lung, spine

ALTERED

BOWEL MOVEMENT

DIARRHEA

CONSTIPATION

DIARRHEA

DEFINITION OF DIARRHEA

Increase in stool water (loose or watery)

Increase in stool weight (>200g/day)

Increase in stool frequency

May be associated with

urgency

perianal dyscomfort

fecal incontinence

>2x /day liquid stool throughout 3 days

Absorbed

8800

9000

Into

200

CLASSIFICATION OF DIARRHEA

AcuteInfectious

Non infectious

Chronic

Funtional

Organic

ACUTE DIARRHEA

Infectiousbacterialviralparasiticmycotic

Non infectioustoxicantibioticsallergyGI bledingothers

Combined e.g. traveller’disease

CLASSIFICATION OF DIARRHEA

Osmotic

Secretory

Inflammatory

Decreased absorptive surface

Motility disorder

Combination of mechanisms – e.g.

OSMOTIC DIARRHEA

Mechanism Example Characteristics

Nonabsorbable molecules Lactase deficiency Watery stool, no blood or

in the gut lumen pus, improves with

fasting

Generalized Stool may contain fat

malabsorption globules or meet fibers

Mg2+ containing

laxatives

Lactulose

Excess of absorbable Sugar Watery diarrhea

molecules Must (Grape juice)

Watery diarrhea

SECRETORY DIARRHEA

Mechanism Example Characteristics

Increased secretion and/or

Decreased absorption of

Na+ or Cl-

Cholera

E coli heat-labile toxin

Bile salt enteropathy

Fatty acid-induced

Diarrhea

Zollinger-Ellison sy.

VIP-secreting tumor

Carcinoid

Large volume, watery

No blood or pus

No solute gap

Little or no response to

fasting

„rice water cholera stool”

1961

Seventh Cholera Pandemic (1961-)new strain of V. cholerae--El Tor strain;

first observed among Indonesian emigres to Egypt in 1905;

emerges as pandemic in 1961

INFLAMMATORY DIARRHEA

Mechanism Example Characteristics

Destruction of mucosa

Impaired absorption

Outpouring of blood,

mucus

Ulcerative colitis

Crohn disease

Shigellosis

Clostridium difficile

Amebiasis

Calcici virus

Rota v.

Norwalk v.

Small frequent stools

With blood and pus

Fever

Clostridium difficile

Pseudomembranous colitis

Increasing incidence of

Clostridium diff. infection

Causes:

Use and Overuse of antibiotics

Widespread and continous use PPIs

DECREASED ABSORPTIVE SURFACE DIARRHEA

Mechanism Example Characteristics

Impaired resorption of

electrolytes

Bowel resection

Enteric fistula

Bariatric surgery

Celiac disease

Variable

Celiac disease

Villous atrophy,

T Lymphocytes

Glutene sensitive

enteropathy

Primate oesophagus as substrate

Celiac disease: Endomysial/transglutaminase antibodies

Antigen: IgA to tissue

transglutaminase

located in the

muscularis mucosa

Up to 100% of the

patients with coeliac

disease (gluten

sensitivity) were positive

for endomysial antibodies.

In patients with IgA

deficiency, assessment of

IgG transglutaminase

and endomysial

antibodies is

reccomended.

IgA deficient endomysial antibodiesAntigen: IgG to tissue transglutaminase

Staining of

network of

fibres around

smooth

muscle cells

in the

muscularis

mucosa.

MOTILITY DISORDER DIARRHEA

Mechanism Example Characteristics

Increased motility with

decreased time for

absorption of electrolytes

and/or nutrients

Decreased motility with

bacterial owergrowth

Hyperthyreoidism

Irritable bowel syndrome

Scleroderma

Diabetic diarrhea

Variable

Malabsorption

STEATORRHEAL CAUSES

Mechanism Example Characteristics

Inraluminal maldigestion

Mucosal malabsorption

Postmucosal obstruction

Pacreatic exocrine

insufficiency

Cholestatic liver diseases

Bacterial overgrowth

Whipple’s diseases

Celiac disease

Lymphangiectasia

Tumor

Trauma

Greasy, foul smelling stool

Difficult-to-flash diarrhea

Weight loss

Irregular fold pattern

and thickened walls

Whipple’s disease

Whipple’s disease

Tropheryma whippelii

Ubiquitous actinomyces

Macrophage dysfuntion

is prerequisite of the

disease

Unusual trilaminal

cell wall

Fluorescent in situ

detection of rRNA

Easy to diagnose and

treat – if you think of it

Tropherhyma

whippelii

bacilli

within the

macrophages

Encephalopathy

(occasionally)

Lymphadenopathy

(same morphology

as gut)

Malabsorption

and diarrhea

Arthritis

(often)

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Whipple’s disease

DIARRHEA CAUSING DRUGS

Gastrointestinal drugsMg-containing drugsMisoprostolOlsalazine

Lipid decreasing drugsClofibrate,GemfibrozilLovastatinProbucol, Orlistat

Cardiac/AntihypertensiveDigitalisQuinidineProcainamideHydralazineBeta-blokkolókACE-gátlókDiuretikumok

Neuropsychiatric drugsLithiumFluoxetine (Prozac)Alprazolam (Xanax)Valproic acidEthosuximideL-Dopa

AntibioticsAmpicillinCephalosporinsErythromycinClindamycin

Oncology drugs

OthersTheophyllineThyroid hormonesColchicineNSAID

LAXATIVES

CONSTIPATION

Constipationcomon problem

M<F

Recent onset Constipation

or

Chronic constipation

CHRONIC CONSTIPATION

< 2x / week (> 12 month) infrequent defecation

or 2 of the below

• < 3x / week

• Straining with defecation (> 25%)

• Hard stools (> 25%)

• Sense of incomplete

fecal evacuation (> 25%)

(Rome criteria)

CHRONIC CONSITPATION GENERALLY RESULTS FROM:

Inadequate fluid intake

Inadequate fiber intake

Disordered colonic transit

Anorectal dysfunction

SECONDARY COUSES OF CHRONIC CONSTIPATION

Neurological diseases

Periferal Central

Megacolon congenitum Multiple sclerosis

Chagas-disease Spinal cord injury

Diabetes mellitus Parkinson-disease

Autonomic neuropathy Stroke

Intestinal pseudo-obstruction

Non neurological abnormalities

Anatomical obstructionDiverticulosisTumorStricture

Psychiatric diseasesDepressionDietary factors

Scleroderma

Endocrinological diseases

Hypothyreosis

Hyper/hypocalcemia

Pregnancy

Porphyria

Panhypopituitarism

Myotonic dystrophy

SECONDARY COUSES OF CHRONIC CONSTIPATION

CAUSES OF CONSTIPATION

Dietary factors – inadequate fluids, low-fiber foods

Physical inactivity – prolonged bed rest, inadequate exercise

Pregnancy

Advanced age

Drugs – long list

Metabolic abnormalities – hypokalemia, hyperglycemia, uremia,

porphyria, amyloidosis

Endocrine – hypothyroidism, hypercalcemia, glucagonoma,

pheochromocytoma

Lower bowel abnormalitiesColon, Rectum, Anus

Anorectal and pelvic floor diseases

Neurological – innervation disorders

Psychogenic disorders

Enema (chronic use)

Home remedies and OTC medications

Dietary fiber (bulk-forming laxatives)

Lubricant laxatives – mineral oil or emulsion

Emollient laxatives

Hyperosmolar laxatives –sorbitol, polyethylene glycol

Saline laxative – magnesium sulphate, Mg-citrate

Stimulant laxatives – cascara, senna, bisacodyl (Dulcolax),

prunes

Enemas

Suppositories – glicerin

Combination products

Treatment: TREAT THE UNDERLINING CAUSE!

Jaundice / Icterus

Liver related – hepatitis, toxic, DILI, Gilbert sy

Biliary obstruction – stone, tumor, stricture

Prehepatic, hemolytic jaundice

corpuscular, extra-corpuscular

Classification of jaundice

Liver diseases

Acute – chronic Focal - diffuse

Classification according to the etiology

Hepatitis –

Viral – HAV, HBV, HCV, HEV, EBV, CM

Autoimmune (AIH), PBC, PSC

Bacterial - Leptospirosis, Syphilis, Brucellosis

Protozoal – Malaria, Tripanosomiasis, Amebiasis

Toxic –

Death cup (Amanita) poisoning

Alcohol – ethanol, methanol

Industrial toxins

Drug induced (DILI)

Paracetamol, NSAID, antimicrobal Ds, Statins, Psychiatric

Circulatory, vascular

Shock, Budd-Chiary, portal vein thrombosis

Focal diseases

Hemangiomas, Cysts, Adenomas, FNH, Tumors: HCC, Metastases

Biliary diseases

Gall stone disease

Cholecystolithiasis

Stone in common bile duct

Mirizzi syndrome

Primary biliary cholangitis (PBC)

Primary sclerosing cholangitis (PSC)

Prevalence: 10-100/1.000.000 (in relatives > 100x)

95% female (30-60 év)

Chronic, intrahepatic cholestasis

Progressive disease

Autoimmun mechanism

Itching is common symptome

Duration variable, 20-30 y

PRIMARY BILIARY CHOLANGITIS (PBC)

DIAGNOSIS

4 pillars

Clinical picture – fatigue, itching, xanthomas

Lab signs of cholestasis - ALP, GGT, Se.bi

Autoantibodies – AMA M2, ANA Sp100, gp210

Exclusion of extrahep.obstr. – US, MRI, ERCP

HISTOLOGY and NATURAL HISTORY

4 stages

I. Small-medium bile duct injury, inflammation

II. Periportal inflammation and bile duct proliferation

III. Granulomas and scarring

IV.Cirrhosis

Primary sclerosing cholangitis (PSC)

Progressive disease

biliary cirrhosis

portal hypertonia

liver failure

Average survival 12 years

Cholangiocarcinoma common (3-10-36%)

intrahepatic 15%, hílar 65% distal 20%

DIAGNOSIS

Chemical laboratory

ALP, GGT, Se. Bilirubin

Autoantibodies – pANCA (85%)

Imaging - US, cholangio MR, ERCP

Histology

TREATMENT

Endoscopic dilatation of dominant stenosis

Antibiotics in case of bacterial cholangitis

Fat soluble A, D, E, K vitamins

LIVER TRANSPLANTATION

Diseases of pancreas

Pancreatitis

Acute

Chronic

Pancreas tumor

ACUTE PANCREATITISESSENTIALS OF DIAGNOSIS

Abrupt onset of deep epigastric pain, often with radiation

to the back.

History of previous episodes, often related to alcohol

intake.

Nausea, vomiting, sweating, weakness.

Abdominal tenderness and distention and fever.

Leukocytosis, elevated serum amylase, elevated serum

lipase, creatinin, LDH, AST(GOT), glucose. Hbg↓, Ca↓

Imaging

• US

• radiographs of the abdomen – gallstones

– sentinel loop (segment of air-filled small intestine)

– colon cutoff sign (gas-filled segment of transverse colon abruptly ending at the area of pancreatic inflammation)

• CT scan - gold standard!

ACUTE PANCREATITIS –IMAGING

Gallstones: 45%

Alcohol: 35%

Other 10%

Medications

Hypercalcemia

Hypertriglyceridemia

Obstructive

Post-ERCP

Hereditary

Trauma

Viral Vascular/ischemic

Postcardiac bypass

Idiopathic: 10%

Causes of Acute Pancreatitis (% of Cases)

Gallstones

45%

Vascular causes and vasculitisischemic-hypoperfusion states after cardiac surgery

Connective tissue disorders and

thrombotic thrombocytopenic purpura (TTP)

Cancer of the pancreas

Hypercalcemia

Periampullary diverticulum

Pancreas divisum

Hereditary pancreatitis

Cystic fibrosis

Renal failure

Uncommon causes

Infections

mumps, coxsackievirus,

cytomegalovirus, echovirus, herpes V.

bacteria: tbc, leptospirosis

parasites ascaris, clonorchis

Scorpion toxin

Autoimmune

e.g., Sjögren's syndrome

Rare causes

Gallstones

Common bile

duct

Biliary pancreatitis

CHRONIC PANCREATITIS

CHRONIC PANCREATITIS – ETIOLOGY

Alcohol 70%

Pancreatic duct obstruction

Tumor

Trauma

Pancreas divisum

Fibrosis

Cystic fibrosis

Hyperlipidemia

Herediter pancreatitis

Tropical pancreatitis

Hyperparathyreoidism

Chronic pancreatitis other 10%

PANCREATIC CANCERIncreasing incidence - 10/100000

Poor prognosis (worst GI tumor) – 5 y survival <5 %

Male > Female

Age related incidence (65-80 y)

Etiology smoking

exogene factors

hyperinsulinemia (Type II DM)

genetic predisposition

Histology 90% ductal

Localization head (70%), body (20%), tail (10%)Diagnosis

Treatment

Obstructive jaundice

Abdominal pain

Loss of body weight

Jaundice

Steatorrhoea

Leading symptoms of P.cancer

INFLAMMATORY BOWEL DISEASES (IBD)

Ulcerative colitis (UC)

Crohn disease (CD)

Localized to colon

Ulcers of mucous membrane

Pseudopolyps

Prone to malignancy

PSC common

Terminal ileum and/or any part of GI tract

Segmental

Transmural - granulomatous

Fistulas, stenosis

No increase in rate of PSC

Differential diagnosis of ULCERATIVE COLITIS

Crohn’s disease

Infectious colitis - detected on stool culture

Shigella –dysenteria

Entamoeba histolytica – protozoon parasyte caused inflammation

Pseudomembranous colitis – Clostridium difficile associated colitis

Ischemic colitis - inadequate blood supply, typically affects the elderly

Radiation colitis - in patients with previous pelvic radiotherapy

Chemical colitis

Malignancy – cancer may present as acute flare of colitis or vice versa

It is important to rule out when the colitis is refractory to the treatment

Differential diagnosis of CROHN DISEASE

Ulcerative colitis –

Intestinal tuberculosis

NSAID enteropathy

Bechet’s disease

Celiac disease

Irritable bowel syndrome

IRRITABLE BOWEL SYNDROME (IBD)

The Rome IV criteria

Recurrent abdominal pain

- on everage, at least 1 day/week in the last 3 months

Associated with two or more of the following criteria:

- Related to defecation

- Association with a change in frequency of stool

- Associated with a change in form (appearance) of stool

IBS Classification

Diarrhea predominant (IBS-D)

Constipation predominant (IBS-C)

Alternating stool pattern (IBS-A)

Postinfectious (IBS-PI)

Differential diagnosis of IBS

Colon cancer

IBD

Thyroid disorders – hyperthyreodism or hypothyroidism

Giardiasis

Carcinoid sy.

Microscopic colitis

Bacterial overgrowth (SIBO)

Eosinophilic gastroenteritis

Celiac disease

Non-celiac gluten sensitivity

Lactose intolarence

Bile acid malabsorption

Dyssynergic defecation

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