Gastro-esophageal reflux disease (GERD)

Condition characterized by reflux of gastric acid content into the esophagus.

Pathophysiology: Following factors play important roles:
1. Lower esophageal sphincter (LES) dysfunction: most important risk factor
2. Hiatus hernia
3. Delayed esophageal emptying
Clinical features:
1. Heartburn: Typically aggravates on: Lying flat after meals; in some pts after alcohol ingestion.
2. A bitter/ sour test in the mouth due to regurgitation of gastric acid.
3. Atypical/ extra‐esophageal manifestation:
a. Chronic cough
b. Hoarseness of voce………………..( Remember ENT days!!!....Reinke’s edema- vocal cord swelling)
c. Non‐cardiac chest pain
Investigation
1. Upper GI endoscopy: Typically shows: reflux esophagitis
2. Esophageal manometry with pH estimation
Treatment
1. Lifestyle modification:
I. Stay upright for approx. half an hour after each meal
II. To raise the head end of the bed during night
2. Medications: H2 blockers/ PPI
Complication: Barrett’s esophagus
Barrett’s esophagus
It is condition where esophageal squamous epithelium is replaced by metaplastic columnar epithelium.
Risk factor: Long standing GERD
Clinical features: Barrett’s itself is usually asymptomatic, long standing symptoms of GERD: Present.
Investigation
1. Upper GI endoscopy: Shows orange, velvety gastric type epithelium in the esophagus
2. Confirmation of diagnosis by mucosal biopsy.
Treatment
1. Medications to treat GERD
2. Endoscopic surveillance:

Complication: Esophageal adenocarcinoma.

 Gastroduodenal diseases
Gastritis/ Duodenitis Gastric/ Duodenal ulcer (Peptic ulcer)
Mucosal inflammation only Breach in the continuity of mucosa
Gastric or Duodenal: ANATOMICALLY They are different BUT for all practical purpose they are “same”!!!
“Itis” or “Ulcer”: PATHOLOGICALLY They are different BUT for all practical purpose they are “same”!!!
Therefore Gastroduodenal pathology includes ALL of these…..
So…GASTRITIS/DUODENITIS/GASTRIC ULCER/DUODENAL ULCER/PEPTIC ULCER
Don’t expect me to “copy+ paste” same answer 5 times!!!
Etiology/ Risk factors:
1. Chronic H.pylori infection Alternative way
2. Non- H.pylori causes 1. Benign etiology 2. Malignancy
 Drugs: NSAIDs/ Steroids Chronic H.pylori infection
 Stress ulcer: Can occur in any critically ill patients Drugs: NSAIDs/ Steroids
 Portal Hypertensive Gastropathy Stress ulcer: Can occur in any critically ill patients
 Malignancy Portal Hypertensive Gastropathy
Clinical features: Any ≥ 1 of the followings
Abdominal Pain:
 Typically epigastric
Acute epigastric pain: Think about-
 Variable duration
Acute ●Gastroduodenal pathology ●Pancreatitis ●Cholecystitis
 Often occurs periodically
 Nature: Dull aching pain/burning
 Aggravating and relieving factors: variable‐ in some food aggravates pain whereas in some empty stomach
aggravates pain
 Radiation to the back should raise the suspicion of:
a. Perforation
b. Pancreatitis
Associated symptoms:
a. Heartburn/ feeling of indigestion
b. Water brush: Regurgitation of bitter/ sour contents with sudden salivation
c. Features usually absent in benign ulcer:
I. Significant vomiting
II. Weight loss However these are not ALWAYS present in malignant ulcer
III. Appetite loss
Anaemia related manifestation: particularly occult bleeders
Bleed‐ Bleeding may be overt or occult Upper GI bleed: Think about: ●Gastroduodenal pathology ●Variceal
Overt bleeding: Hematemesis and/ or Melena……
 Blood loss may be mild/ moderate/ massive enough to make the patient’s hemodynamics unstable
 In hematemesis, the colour of blood may be fresh/ altered red coloured depending on the time elapsed between
onset of bleeding and vomiting.
 PR examination reveals melena in stool
Occult bleeding: these patients often present with Anaemia related manifestation with or without Abdominal
pain/associated symptoms Anaemia with NO OBVIOUS GI bleed: still ALWAYS Think about!
Collapse: due to massive GI bleed ●Occult Gastroduodenal disease ●Occult Portal Hypertensive Gastropathy
Drug history: H/O intake of an “offending” drug MAY BE present‐ NSAID(“pain killers”)/ Steroid
(Don’t forget Aspirin…it’s an NSAID!! but because it’s principal use is for thrombosis prevention (antiplatelet effect) often
patients describe this as “heart or brain medicine” rather than painkiller )
Sign: Any ≥ 1 of the followings
Anaemia
BP: hypotension if massive bleed:
Circulatory disturbance: if massive bleed: tachycardia/weak pulse
“Digital” examination PR examination reveals melena in stool
Epigastrium
 Tenderness: may be present
 Lump: if present is highly suspicious of malignancy
Investigations
A.Blood:
1. Hb, TC, DC, CRP: Hb MAY BE low depending on the amount of blood lost
2. If no OVERT bleeding but iron deficiency anemia is suspected:
 Serum iron studies:Iron/Ferritin/Transferrin saturation
3. Renal function: Na+ K+ Urea Creatinine
4. Lipase ± Amylase: To rule out acute pancreatitis
5. Clotting profile: Platelet count, BT, CT, PT, aPTT, INR (if active/Overt bleeding)
B.Faecal occult blood test (FOBT)
C.Upper GI Endoscopy:
a. Confirms presence of ulcer/inflammation & their exact anatomical location
b. Helps to confirm atleast 2 of the common etiologies:
 Endoscopic Biopsy confirms histopathological nature of the ulcer‐ benign/malignant
 Diagnosis of H.pylori infection: Rapid urease test
Treatment
Gastroduodenopathy….”itis”/ulcer
Supportive treatment Definitive treatment
Required for GI BLEED Etiological treatment

Supportive treatment: for those with significant GI bleed: ≥1 of the followings

A. Admit if ongoing bleeding or significant bleeding
Airway: To be protected particularly if there is risk of aspiration
B. Breathing: Oxygen
Bowel rest: Nil by mouth till bleeding is under control, nasogastric suction
C. Circulation:
I. IV fluid resuscitation followed by maintenance fluid: Ringer lactate/ Normal saline
II. Blood transfusion
D. Drugs: Infusion of PPI: Pantoprazole for at least 48 hours
E. Endoscopy:
I. Urgent endoscopy: to confirm the diagnosis
II. Endoscopic interventional therapy to ARREST BLEEDING
 Injection therapy: solutions of diluted epinephrine
 Thermal coagulation
Etiological treatment: for bleeders as well as non-bleeders
H.pylori +Ve H.pylori –Ve:

Eradication of H. pylori: “Triple therapy”= 2 antibiotics + PPI PPI for at least 4‐6 weeks
Standard regime: Amoxicillin+ Clarithromycin + any PPI: for 14 days Stop any offending drug‐ NSAID/Steroid
Followed by
Any PPI for atleast another 4‐6 weeks
 Diagnosis of H.pylori infection:………(NOT a “must read” topic!!)
a. Endoscopically: Rapid urease test (RUT)
RUT / CLO test (Campylobacter‐Like Organism), is a rapid diagnostic test for diagnosis of Helicobacter pylori.
The basis of the test is the ability of H. pylori to secrete the urease enzyme, which catalyzes the conversion of Urea to
NH3 & CO2. The test is performed at the time of Endoscopy. A biopsy of mucosa is taken from the stomach/duodenum,
and is placed into a medium containing urea and an indicator such as phenol red. The urease produced by H.
pylori hydrolyzes urea to ammonia, which raises the pH of the medium, and changes the color of the specimen from
yellow (NEGATIVE) to red (POSITIVE).
b. Non-endoscopically: 1. Urea breath test 2. H.pylori fecal antigen 3. Blood serology for H pylori
Acute Pancreatitis
Acute inflammation of pancreas.
Causes:
1. Alcohol Autoimmune diseases Abdominal trauma
2. Biliary disease: Gall stone
3. ↑↑Calcium 1 & 2‐ COMMONEST causes
4. Cystic Fibrosis
5. Dyslipidemia: Hypertriglyceridemia
6. Drug induced: steroid/ Valproate/Thiazides
7. ERCP‐ complication of ERCP
Signs and symptoms: 1. Due to Pancreatitis itself 2. Due to complications, IF any
System Symptoms Signs
Abdomen Onset: Sudden/Rapidly developing 1.Epigastric Lump
Site: Epigastrium  Pseudocyst/Pancreatic Phlegmon
2.Signs of paralytic ileus
Character: Deep seated/dull may be excruciating
PAIN (NOT a Burning pain/ Cramp)  Abdominal distension
Radiation: To the back but NOT ALWAYS  Reduced bowel sound
May Aggravate on: Supine position/Postprandial3.Signs of peritonitis
May Relieved by: Stooping forwards with trunk  Guarding/Rigidity
flexed and knees drawn up Cullen sign: hemorrhagic discoloration of the
(aggravation/relief: MAY not occur) umbilical area due to intraperitoneal hemorrhage
Associated with Grey Turner: hemorrhagic discoloration of the
left flank associated with acute hemorrhagic
Severe nausea ± retching ± vomiting
pancreatitis.
Features due to Complications- may be develop rapidly within few hrs - days
Breathing ARDS: SOB Tachypnoea; ↓SpO2; Bilateral crepitations

Circulation Altered sensorium BP: Hypotension

Dry skin/mucous membrane CRT‐ prolonged
Decreased Urine output Extremity: Tachycardia/ Weak pulse
Dermal Erythematous skin lesion due to subcutaneous fat
necrosis
Eye Eye: Jaundice may be present Icterus may be present
Mechanism: Inflammation of the head of
pancreas may lead to CBD obstruction.
Fever

Acute epigastric pain: Think about- Acute ●Gastroduodenal pathology ●Pancreatitis ●Cholecystitis ●Hepatitis
Acute epigastric pain with Circulatory compromise( “Shock”/ “Collapse”/”hemodynamically unstable”)
Think about- Acute ●Gastroduodenal pathology ●Pancreatitis
(shock due to bleed) (shock due to 3rd spacing)
Investigations
1. To confirm the diagnosis of acute pancreatitis 2. To detect risk factors and complications of acute pancreatitis
1. Blood:
1.Hb, TC, DC CRP
 Hb: ↓ in hemorrhagic pancreatitis
 TC, DC, CRP: ↑inflammation or intra‐abdominal infection‐ Necrotizing pancreatitis, Peri pancreatic abscess
2.Renal function: Na+/ K+/ Urea/Creatinine (To look for any dehydration)
3.LFT: Mild derangement due to “nonspecific” hepatitis:
4.Pancreatic enzymes: Amylase or Lipase levels at least 3 times above the reference range are considered diagnostic
of acute pancreatitis.
However, there are other Intra as well as Extra-abdominal causes of elevation of serum Amylase. Lipase is more
PANCREAS SPECIFIC & has a longer half‐life, so it’s MORE useful if there is a delay between the onset of pain and
the time the patient seeks medical attention.
Elevated lipase levels are more specific for pancreas than elevated amylase levels.
The level of serum amylase or lipase does not indicate whether the disease is mild, moderate, or severe
5.ABG: To look for: Metabolic acidosis/ ↓pO2.
6.Ca level:
 Hypercalcemia is a risk factor of acute pancreatitis
 Acute pancreatitis leads to hypocalcaemia (by saponification of fat)
7.Fasting lipid profile
2. Chest X Ray: To look for: ARDS/Pleural effusion.
3. USG abdomen: 4. CECT abdomen:
To look for: To look particularly for:
 Inflammation of pancreas  Necrotizing pancreatitis
 Gallbladder stone  Peripancreatic abscess
 CBD dilatation  Pancreatic pseudocyst
 Ascites
5. Aspiration of ascitic and pleural fluid: Show elevated levels of amylase and lipase.
Treatment
Acute Pancreatitis

Supportive: Medical Management Interventional treatment Treat/Remove etiology

Basic supportive Organ support Non surgical Surgical

(if Multi-organ failure) (for Loco-regional complication)

Supportive treatment
A. Absolute bed rest till condition stabilizes
B. Breathing: Ventilator‐ for ARDS
B. Bowel rest:
 Nil by mouth initially till clinical improvement starts
 Ryle’s tube suction (if required)
 Gradual introduction of enteral feeding
 If required: Total Parenteral Nutrition
C. Maintain circulation:IV fluid : amount + rate + duration depends on clinical status‐ Bolus +/‐ maintenance
C. Catheterisation: To monitor urine output: if circulatory disturbance/Renal failure is present
D. Drugs (Supportive):
 Analgesic‐antispasmodic:  Antibiotics (particularly if intra‐abdominal
Drotaverine infection is suspected): Imipenem
Opioids: Tramadol/ Pethidine  Antifungal (if intra‐abdominal fungal infection)
Avoid morphine as it constricts sphincter of OD  Anti‐ulcer drugs: To avoid stress ulcer: PPI

D. Diet: Gradual introduction of normal diet: Initially clear liquid; then semisolid/soft diet; then normal diet
D. DVT prophylaxis till immobile
E. External Intervention
 Interventional treatment
A. Percutaneous drainage of peripancreatic abscess/ infected pseudocyst
B. ascites/ pleural effusion‐ rarely significant in amount requiring drainage
 Surgical treatment
A. Necrosectomy/ debridement in necrotizing pancreatitis
E. Etiological treatment: treat/address the etiology…eg.
 Early cholecystectomy in case of gallstone pancreatitis
 STOP alcohol
 STOP the offending drug
Complications of acute pancreatitis‐ ‘’PANCREAS’’
Organ Complications
Pancreatic 1. Necrosis
2. Hemorrhage
3. Pancreatic pseudocyst (sterile/ infected)
4. Peripancreatic abscess
Abdomen 1. Ascites
2. Paralytic ileus
3. Peritonitis
Neurological Encephalopathy
Circulatory Circulatory shock/ collapse
Respiratory 1. ARDS
2. Pleural effusion‐ It results from leakage of pancreatic fluid through small pores in the
diaphragm into the pleural cavity
Eye Purtscher’s retinopathy (Sudden blindness due to vaso‐occlusive and Hemorrhagic vasculopathy)
AKI Acute tubular necrosis (ATN) leading to AKI
Skin Subcutaneous fat necrosis

Ranson’s criteria/ score….(”For Short Note obsessed”)

A predictive score which can reasonably predict prognosis/ development of complication(s) in an acute pancreatitis.
On admission Within first 48 hours
1. Age >55 years 1. Arterial PO2 < 60 mm Hg 4. Ca++ <8 mg/dL
2. WBC count > 16000/cu.mm 2. BUN value increases by > 5 mg/dL 5. Drop in hematocrit: >10%
3. Blood glucose >200 mg/dl (BUN/2.8) = Urea 6. Estimated fluid deficit >6L
4. AST >250 U/L 3. Base deficit >4 mEq/L
5. Serum LDH >350 U/L
Presence of ≥3 of the above Presence of ≥1 of the above predicts worse prognosis
predicts a complicated course
 Hyperamylasemia……..(for Short note “obsessive lovers”)
1. Abdominal causes: 2. Extra ‐abdominal causes:
 Acute/ chronic pancreatitis  Salivary gland diseases: Mumps/
 Perforation: Bowel/ peptic Sialolithiasis (stone)/ tumor
 Bowel infarction  Bronchogenic carcinoma
 Acute cholecystitis  Ovarian carcinoma
 Ectopic pregnancy (ruptured)
Malabsorption syndrome
A group of disorders characterized by impaired absorption of different food particles and nutrients.
Examples/Causes/Types:
1. Bacterial overgrowth syndrome 4. Crohn’s Disease
2. Short bowel syndrome (post‐resection): 5. Dietary Intolerance: Lactose Intolerance/
Terminal ileum/Extensive small intestinal resection 6. Enteropathy: Protein losing enteropathy
3. Celiac disease
Mechanism of clinical manifestations and clinical features:
1. Due to Malabsorption of different nutrients: ≥ 1 OF THESE
2. “Unique” feature(s) of the disease: some of them, apart from malabsorption, cause OTHER manifestations
Substances malabsorbed/deficient Clinical features
A Albumin Swelling (anasarca)
Fat Steatorrhoea
Flatulence
B Bile acids Vitamin A Night blindness
Vitamin D Osteomalacia/Osteoporosis‐ Bone pain/deformity/fracture
Vitamin E CNS manifestations
Vitamin K Coagulopathy
Vitamin B12 Anemia ± Neurological complications
C Ca++ Tetany‐ spontaneous muscle spasm/Paresthesia (perioral)
Diet (Protein + Carbohydrate + Fat) Weight loss/Weakness/Wasting
D Vitamin D Proximal myopathy/Musculoskeletal pain/Bony deformity
E Electrolytes Sodium Encephalopathy
Potassium Muscle atony‐ Constipation/Distension
F Fe++ Iron deficiency anemia
Fluid Watery diarrhea
Fat Steatorrhoea
Investigations: To look for evidence of malabsorption & to detect its consequences
Blood:
1.Hb, TC, DC, CRP, MCV: Hb: ↓ (in Iron deficiency/ vitamin B12 deficiency) MCV: ↓/↑ (depending on the cause).
2.Iron studies:Serum Iron/Serum Ferritin/ Serum Transferrin saturation
3. Biochemistry:Na+/K+/Ca++/Mg++/Urea, Creatinine
Clotting profile
Serum Vitamin B12 level + Folate level+ Vit D3 level
Serum Albumin
4.Tests to confirm Malabsorption:
Fecal fat content: ↑
D‐Xylose test
5.Tests to confirm the underlying disease: Intestinal mucosal biopsy: Often confirm the diagnosis in some of the cases.
Treatment:
1.General treatment
1. Nutritional support‐ Dieatary +/‐ fluid replenishment
2. Supplementation of vitamins and minerals
2.Specific treatment- depends on the underlying disease

Inflammatory bowel disease (IBD)

It is a condition characterized by widespread inflammatory damage to different parts of small and large intestine.
The pattern of inflammation and subsequent clinical features lead to 2 distinct clinical entities:
1. Crohn’s disease 2. Ulcerative colitis.
Crohn’s disease
Characterized by relapsing and remitting segmental/ patchy inflammation of intestine.
Sites (according to descending order of frequency):
1. Terminal ileum and proximal ascending colon: Ileocolitis
2. Terminal ileum: Ileitis
3. Large gut: Colitis‐ however, involvement of sigmoid colon and rectum is extremely rare and this variety is
usually associated with perianal manifestations.
Clinical features:
Mechanism of clinical manifestations: Manifestations can be chronic/rapid/acute on chronic‐ they may come back after
a quiscent stage when the disease flares up

Extra-intestinal features

Clinical features of ileocolitis:

1. Due to chronic inflammation:
1. Pain abdomen: Often in right iliac fossa 4. RIF‐tenderness / mass may be present
2. Diarrhea Usually watery, rarely bloody (matted intestine + lymph nodes + mesentery)
3. Fever, loss of appetite and weight loss 5. F/O Malabsorption syndro
2. Due to intestinal obstruction (fibrostenotic occlusion of intestine): Acute/Subacute
1. Abdominal pain 4. Distension
2. Borborygmi/Bloating 5. Emesis (Vomiting)
3. Constipation 6. Feces/Flatus
3. Due to fistulisation:
1. Enterocolic fistula: Malabsorption 3. Enterovaginal fistula: Feculent per‐vaginal
2. Enterovesicle fistula: Feculent urine discharge
4. Enteromesenteric fistula: Intra‐abdominal abscess
Clinical features of perianal disease:
1. Perianal fistula 3. Visible anal skin tag
2. Perianal abscess 4. Anal fissure
The disease classically relapses and remits.
Investigation
1.Blood: Hb, TC, DC, CRP/ESR‐ TC, DC, CRP, ESR: ↑ due to inflammation/ intra‐abdominal infection
Hb: ↓ due to: Chronic inflammation/ Iron deficiency/ B12 deficiency
2.Renal function: Na+ K+ Urea Creatinine
3.If malabsorption is suspected: Albumin, Serum Ca++, Vitamin B12, Vitamin D, Iron studies
4.Stool: Look for ova/ parasites/ cysts. Fecal Calprotectin level: High( “Inflammatory marker” of Intestine)
5.Colonoscopy: shows mucosal inflammation/ ulceration with skip areas. Colonoscopic biopsy confirm the diagnosis.
6.CECT abdomen: To visualize the intestine for any obvious anatomical abnormality/ distortion(stricture/fistula)

Supportive treatment: ≥1 relevant if patient is very sick

1. Admit‐ if severe diarrhea/volume depletion
2. Bowel rest‐ NPM till clinically improved
3. Circulation‐ IV fluid in severe diarrhea‐ Bolus & maintenance depending on the clinical scenario
4. Catheterisation‐ To monitor urine output‐ if required
5. Drugs:
Analgesic/Antispasmodic: Drotaverine/ Dicyclomine.
Antidiarrhoeal: Loperamide (May cause paralytic ileus)
Antibiotic‐ often given empirically
Specific treatment:
1. Aminosalicylate: To maintain remission- No longer the first line drug, can be used as adjunct with Steroid
 Drugs: Mesalamine/Olsalazine/Balsalazide: No longer the first line drug, can be used as adjunct with Steroid
2. Corticosteroid: DOC in most CD patients to achieve remission
 Systemic corticosteroids: Prednisolone/ Methylprednisolone
3. Immunomodulators: Used in moderate to severe disease‐ To induce + to maintain remission
● Non biologics: Azathioprine/Methotrexate/Ciclosporine ● Biological agents: Infliximab/ Natalizumab

Surgery: In medically refractory cases/for complications‐ Ilectomy/Ileocolectomy

Ulcerative colitis
Characterized by relapsing and remitting inflammation of the colon which is continuous.
Common sites:
1.Sigmoid colon + rectum: Proctosigmoiditis 2.Left side of colon: Left sided colitis 3.Pancolitis
Clinical features: Manifestations can be chronic/rapid/acute on chronic‐ they may come back after a quiscent stage
when the disease flares up
Mechanism of clinical manifestations:1. Due to chronic inflammation 2. Due to toxic megacolon 3. Extra‐intestinal

1. Clinical features due to chronic inflammation:

1. Bloody/Non bloody diarrhoea
2. Hemodynamic instability ± Pallor
3. Abdo pain: LUQ/LLQ pain: continuous/ spasmodic
4. Constitutional: Fever, weight loss, loss of appetite

2. Clinical features due to toxic megacolon: Toxic megacolon, a potentially lethal condition, is a nonobstructive colonic
dilatation larger than 6cm with signs of systemic toxicity
1. Abdominal pain ± Distension
2. Abdominal tenderness
3. Sluggish bowel sound
4. Toxicity: Fever, tachycardia, flushing
Severity of UC-Helps to assess disease activity

Criteria Mild Moderate Severe

Number of stools/day <4 4‐6 >6
Weight loss (% of body weight) None 1‐10% >10%
Pulse < 90 90‐100 >100
Fever None 99‐100 ⁰F >100 ⁰F
Hematocrit (PCV) Normal 30‐40% <30%
ESR <20 mm/hr 20‐30 mm/hr >30 mm/hr
Albumin (gm/dL) Normal 3‐3.5 <3

Extra-intestinal manifestations: same for both UC & CD….(SN)

Ocular: Uveitis + Episcleritis Liver: Primary sclerosing cholangitis
Lungs: Interstitial lung disease Kidney: Nephrolithiasis
Heart: Non‐infective endocarditis Skin:Erythema nodosum; Pyoderma gangrinosum.
Abdomen: Gall stone (more common in CD) Joints: Seronegative Spondyloarthropathy; Polyarthritis

Investigation
1. Blood: Hb, TC, DC, CRP/ESR‐ Hb: ↓ due to blood loss TC, DC, CRP, ESR: ↑ inflammation/ intra‐abdominal infection
2. Renal function: Na+ K+ Urea Creatinine‐To look for dehydration
3. Serum albumin level
4. Stool: Look for ovum/ parasite/ cyst/ Gram stain, culture and sensitivity Fecal Calprotectin‐ High
5. Straight X Ray abdomen: To look for toxic megacolon (diagnosed when colonic diameter is >6 cm.)
6. Sigmoidoscopy/ Colonoscopy: Will visualize inflamed, ulcerated mucosa and biopsy confirms the diagnosis
7. CECT abdomen: To look for any structural abnormality
Treatment 1. Supportive treatment 2. Specific treatment 3. Surgical treatment
1. Supportive treatment- ≥1 relevant if patient is very sick
Admit if very sick
Bowel rest‐ nil by mouth till acute phase is over
Circulation ‐IV fluid – Bolus +/‐ Maintenance fluid depending on volume status
Blood transfusion‐ if required
Drugs: Antidiarrhoeal‐ Loperamide ( with caution, best avoided during active flare up!!)
Analgesic‐antispasmodic: Drotaverine
Antibiotic (Particularly if toxic megacolon is suspected): Cefuroxime /Pip‐Taz + Metronidazole
Emergency Rx for toxic megacolon:
1. Nil per mouth 4. Colonic decompression by: Flatus tube/ Colonoscopic
2. IV antibiotic‐ Pip‐Taz + Metronidazole 5. Surgery‐ Partial Colectomy
3. IV Hydrocortisone
2. Specific treatment
1. ASA compounds: To achieve and to maintain remission
Usually 1st line therapy in mild disease: Mesalamine/ Osalazine/ Balsalazine: PO/PR preparation
2. Corticosteroids: To achieve remission in Moderate to severe ulcerative colitis
1. Prednisolone/Methylprednisolone: PO/IV 2. Hydrocortisone: Enema/ foam
3. Immunomodulators: To achieve and to maintain remsission- Moderate to severe ulcerative colitis
Non biologics: Cyclosporine Biological agents: Infliximab
3. Surgery: Surgery is done in medically refractory cases/ for complications- Partial/ hemicolectomy
 Difference between Crohn’s disease and Ulcerative colitis

Points Crohn’s disease Ulcerative colitis

Pattern of inflammation Patchy/ skip lesion Continuous
Site Ileocolitis, ileitis, colitis Proctosigmoiditis, left sided colitis, Pancolitis
Diarrhoea Not bloody Bloody
Malabsorption + -
Fistulisation + -
Perianal disease + -
Intestinal obstruction + -
Toxic megacolon - +

Irritable bowel syndrome (IBS)

Characterized by widespread GI manifestations in absence of any biochemical/ structural abnormality.
Pathogenesis: Usually the following 4 factors play important role:
1.Intestinal dysmotility 3.Enteric infection/ altered gut flora
2.Intestinal hypersensitivity to pain 4.Psychological factors
Clinical features:
1. Abdominal pain: Often lower abdominal- continuous/episodic‐Typically associated with >1 of the following:
1. Relieved after defecation
2. Change in the form/ appearance/ consistency of stool (hard / semisolid/ liquid)
3. Change in stool frequency
(Rome Criteria of IBS: Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated
with two or more of the ABOVE)
2. Abdominal symptoms: 4. Absent symptoms:
1. Mucoid stool 1. Nocturnal diarrhea
2. Urgency/ frequency 2. Weight loss
3. Associated manifestations: 3. Per‐rectal bleeding
1. Chest pain 4. Alternate constipation and diarrhoea
2. Palpitation
3. Pain at different sites of the body
4. Heartburn

Investigation IBS can be diagnosed from typical history, still organic diseases must be ruled out by investigations
1. Blood: Hb, TC, DC, CRP
2. Serum albumin, serum Ca++, iron studies (to rule out malabsorption)
3. Stool: OPC/ Gram stain/C.C. Faecal calprotectin: If ↑: indicates inflammatory diarrhea.
4. Colonoscopy: To rule out any structural lesion
Treatment
1. Appropriate dietary modification 6. Anti-depressants:
2. Antispasmodic: Drotaverine/Mebeverine Mechanism of action:
3. Anti-diarrheal: Loperamide a. Centrally acting pain inhibitors
4. Anti-constipation agent (Laxatives): b. Anti‐cholinergic effect.
Magnesium salts/ Poly‐ethylene‐glycol Commonly used agents are:
5. Probiotics: Lactobacillus spore
Amitriptyline/Imipramine/Fluoxetine/Paroxetine
7. Psychological counselling
 Blind loop syndrome/Bacterial Overgrowth Syndrome
Blind loop syndrome occurs when part of the small intestine forms a loop that food bypasses during digestion so food
particle cannot move normally through the GIT. Slowly moving food and waste products become a breeding ground
for bacteria. So it is also called Bacterial Overgrowth Syndrome.
(Bacterial overgrowth syndrome occurs when the normally low number of bacteria that inhabit the stomach,
duodenum, jejunum, and proximal ileum significantly increases or becomes overtaken by other pathogens)
Causes- ‘’Blind loops’’ from the following may result in bacterial overgrowth syndrome:
1.Side‐to‐side or end‐to‐side anastomoses 3.Segmental dilatation of the ileum
2.Duodenal or jejunal diverticula 4.Biliopancreatic diversion

Mechanism of clinical manifestations and clinical features:

1. Due to Malabsorption of different nutrients: ≥ 1 OF THESE
Substances malabsorbed/deficient Clinical features
A Albumin Swelling (anasarca)
Fat Steatorrhoea
Flatulence
B Bile acids Vitamin A Night blindness
Vitamin D Osteomalacia/Osteoporosis‐ Bone pain/deformity/fracture
Vitamin E CNS manifestations
Vitamin K Coagulopathy
Vitamin B12 Anemia ± Neurological complications
C Ca++ Tetany‐ spontaneous muscle spasm/Paresthesia (perioral)
Diet (Protein + Carbohydrate + Fat) Weight loss/Weakness/Wasting
D Vitamin D Proximal myopathy/Musculoskeletal pain/Bony deformity
E Electrolytes Sodium Encephalopathy
Potassium Muscle atony‐ Constipation/Distension
F Fe++ Iron deficiency anemia
Fluid Watery diarrhea
Fat Steatorrhoea
2. “Unique” feature(s) of the disease: apart from malabsorption, cause OTHER manifestations
 h/o abdominal surgery‐ often present
Investigaton: Abdominal x‐ray/Abdominal CT scan/Contrast enema study
Treatment
Medical- Antibiotic‐ Tetracycline/ Rifaximin
Surgical- Repair of the defect and blind loop
Replenish‐ deficient nutrients
Celiac disease
Celiac disease (gluten‐sensitive enteropathy), is a chronic disorder of the GIT that results in an inability to tolerate
gliadin‐the alcohol‐soluble fraction of gluten.
Gluten is a protein commonly found in wheat, rye, and barley. When patients with celiac disease ingest gliadin, an
immunologically mediated inflammatory response occurs that damages the mucosa of their intestines, resulting in
maldigestion and malabsorption of food nutrients.
Symptoms & Signs
1. Due to Malabsorption of different nutrients: ≥ 1 OF THESE…see above!!
2. “Unique” feature(s) of the disease: apart from malabsorption, cause OTHER manifestations
 Endocrinopathy‐a.Amenorrhea b.Delayed menarche c.Impotence/Infertility
 Dermatitis herpetiformis‐ pruritic, papulovesicular lesions on the extensor surfaces of the extremities, trunk
Investigations
1.Blood
Electrolytes and chemistries – Albumin, Urea, Creatinine, Na, K, Ca, Clotting profile
Hematologic tests – Hb, Iron study, Vit B12/Folate
Confirmatory test: Serum IgA antibodies- Anti-tissue transglutaminase antibody (IgA TTG)
2.Stool examination –Increased Fat content due to Fat malabsorption
3.Endoscopy and biopsy- Duodenal biopsy‐ villous atrophy + Total mucosal hypoplasia
Management: Removal of gluten from the diet is essential

Whipple disease
Whipple disease is a systemic disease caused by a gram positive bacterium Tropheryma whippelii.
C/F
Symptoms & Signs
3. Due to Malabsorption of different nutrients: ≥ 1 OF THESE…see above!!
4. “Unique” feature(s) of the disease: apart from malabsorption, cause OTHER manifestations
 CNS
a.Dementia
b.Meningoencephalitis
c.Ataxia/Involuntary movement
 CVS‐ Valvular lesion
Investigations
1. Blood
Electrolytes and chemistries – Albumin, Urea, Creatinine, Na, K, Ca, Clotting profile
Hematologic tests – Hb, Iron study, Vit B12/Folate
2. Stool examination ‐ Fat malabsorption
3. Endoscopy and biopsy- Small bowel biopsies show villi containing macrophages staining positive with periodic acid‐
schiff (PAS)stain.
Treatment- Because of the tendency of whipple disease to relapse on short courses of antibiotics, most authorities
suggest a prolonged course (upto 1 y)‐ TMP/SZ or Penicillin or Chloramphenicol
 Portal hypertension
Characterized by an elevated portal venous pressure (normal: 9‐10 mm Hg).

Causes/Types: grouped according to the “site” of the underlying DISEASE

1. Intra-hepatic cause:
Alternative way…..
 Cirrhosis ….most common cause
Portal Htn. causes
 Non cirrhotic portal Fibrosis
2. Pre-hepatic causes: 1. Cirrhosis
 Portal vein thrombosis 2. Non- cirrhotic etiologies
 Splenic vein thrombosis Hope you don’t expect any
further details!!
3. Post-hepatic cause:
 Hepatic vein thrombosis (Budd Chiari syndrome)
 IVC obstruction:
o Tumor invasion
o Thrombus (rare)
 Long standing systemic venous congestion
o RHF
o Constrictive pericarditis
Pathophysiological basis of Clinical features of Portal HTn: ≥ 1 of the following may appear in ANY ORDER
Pathophysiological changes Relevant clinical features
Elevated portal venous hydrostatic pressure A Ascites
Opening up of Porto‐Caval collaterals B Bleeding varices GI bleeding/ (at gastro‐esophageal
(Porto‐Systemic collaterals) junction)

C Collaterals‐ Venous prominence at superficial abdominal

wall with direction of filling “away from the umbilicus”
(Caput medusae - visible collaterals surrounding umbilicus)
PV congestion  Splenic vein congestion C Congestive splenomegaly
D Disease‐ f/o underlying disease responsible for P. Htn
Toxic products of digestion bypass the liver and E Brain: Encephalopathy‐ Portocaval/ hepatic encephalopathy
reaches systemic circulation through collateral
F Lung: Fetor hepaticus
Splanchnic (GI) congestion G Congestive gastropathy
Clinical features: Silent= Asymptomatic OR ≥ 1 of the following may appear in ANY ORDER
A Ascites: Abdominal swelling
B Bleeding varices: Hematemesis and/or Melena (Black semisolid stool)
It may progress into hemodynamic instability.
C Caput medusae (collateral at periumbilical region) and superficial abdominal venous prominence:
Direction of filling is away from umbilicus
Congestive splenomegaly
D Features of the underlying disease
E Portosystemic encephalopathy
F Fetor hepaticus (sweetish/ ammoniacal smell in the breath of the patient due to presence of mercaptan)
G Gastropathy (causing non‐specific abdominal symptoms)
H Hypersplenism (peripheral destruction of blood cells due to hyperactive reticuloendothelial [RE] cells of spleen)
Investigation:
a. Blood: TC, DC (Pancytopenia due to hypersplenism)
1. FBC+ ESR/CRP 3. Coagulation profile: PT, aPTT, INR.
Hb: ↓ (due to GI bleed) 4. LFT: Bilirubin, Albumin, transaminase
2. Renal function: Na+/ K+ / Urea/ Creatinine
b. USG upper abdomen:
Shows portal venous diameter which can roughly a. May show splenomegaly
predict hypertension i b. Show any cirrhotic changes
Detect ascites
c. Upper GI endoscopy: To look for any varices
d. Other relevant investigations to assess the underlying cause.
Treatment:
Supportive: Definitive:
Treatment of:
1. Ascites
2. GI bleed
3. Encephalopathy
4. Gastropathy
Complications:
1. Ascites 4. Encephalopathy
2. GI bleed 5. Gastropathy
3. Congestive splenomegaly 6. Hypersplenism

Liver/Hepatocellular disease/damage/dysfunction

Types and causes: Acute/ Chronic depends on the Cause

Acute: Rapid progression Chronic: Slow progression of liver disease

Acetaminophen (Paracetamol) overdose Alcohol
Acute viral hepatitis (HAV, HBV; HDV; HEV) Autoimmune hepatitis “CAUSES OF CIRRHOSIS”
all EXCEPT cancer & drug
Autoimmune hepatitis Budd Chiari Syndrome
Budd Chiari syndrome Biliary cirrhosis (Primary/ Secondary)
Cardiogenic shock (Shock liver) Chronic hepatitis (HCV, HBV)
Drug induced liver injury(DILI) Cancer:
Exogenous toxin (Amanita phalloides, Aflatoxin) o Primary: Hepatocellular Carcinoma
o Secondary: Hepatic metastasis
Deposition:
o Cu: Wilson
o Fe: Hemochromatosis
o Amyloidosis
Drug induced liver injury(DILI)
Fatty Liver: Non‐alcoholic fatty liver disease (NAFLD)
 Some of the “causes” can damage the Liver in “both” ways
 “Chronic” etiologies when damage the liver
 Pre/Non cirrhotic stage of liver disease
 Cirrhosis
 From a clinical point of view Causes of Chronic Liver Disease (CLD) are…..
1.Alcoholic Liver disease 2.Rest of them= Non‐Alcoholic causes
 Diseased/ damaged LIVER

“Acute” etiology “Gradual” etiology

THE LIVER
THE LIVER: never becomes fibrotic Pre‐FIBROTIC stage

Acute Hepatocellular dysfunction Chronic Hepatocellular dysfunction FIBROTIC LIVER

Manifestation due to hepatocellular dysfunction
Sinusoidial resistance increases
Acute Liver disease & Pre-FIBROTIC stage of Chronic Liver disease
No Portal Hypertension Portal Hypertension
Let’s REVISE!!!!!
Acutely damaged Liver: Hepatocellular dysfunction BUT No Portal Hypertension
Chronic Liver disease:
 Pre/Non- Cirrhotic stage: Hepatocellular dysfunction BUT No Portal Hypertension
 Cirrhotic stage: Hepatocellular dysfunction AND Portal Hypertension
Let’s “REre”vise!!............................A diseased Liver IS NOT ALWAYS A CIRHHOTIC LIVER
Let’s conclude……. “Liver er case…toke to CIRRHOSIS bolei daNr korate hobey”….
My answer: Case ta daNriye jabe Kintu Daktar hoye aar daNrate parbo na
Pathophysiology effects of hepatocellular damage/ disease/failure
• Derangement of synthetic function of liver: Albumin & clotting factor synthesis
• Derangement of metabolic function: Bilirubin metabolism
• Derangement of detoxifying function: detoxifies metabolically generated waste/toxin( PV brings them to the liver)
• Derangement of hormone metabolism
• Derangement of synthesis and metabolism of endogenous vasoconstrictor and vasodilator
• Derangement of carbohydrate+ protein + fat metabolism
Clinical effects/manifestations of Liver disease: Asymptomatic!! OR ≥ 1 of the followings may appear in ANY order
Anasarca: (hypoalbuminemia)
Bilirubinemia‐ Jaundice (deranged Bilirubin metabolism)
Constituitional: Anorexia/Nausea/Weakness
Coagulopathy(deranged clotting factor synthesis)‐ Asymptomatic OR Spontaneous bleeding
Disease‐ ANY unique/specific manifestation of the UNDERLYING Etiology‐ depends on the disease
Encephalopathy (Accumulation of toxic metabolic waste products due to deranged detoxifying function)
A. Altered sensorium D. Delirium, disturbed sleep rhythm (reversal of sleep‐
B. Behavioral change (Indifference to others, childish wake cycle), disturbed mood
behavior) E. Features of cerebral edema (due to ↑ICT)
C. Confusion, coma, convulsion F. Flapping tremor
G. ↓GCS.
Fetor hepaticus
Glycemic
Hepato renal syndrome Derangement of synthesis and metabolism of endogenous vasoconstrictor and vasodilator
leads to an IMBALANCE which adversely affect Renal and Pulmonary Hemodynamics
Hepatopulmonary syndrome
Hyperestrogenemia: deranged metabolism of Testosterone leads to EXCESSIVE peripheral conversion to Estrogen
1. Testicular atrophy 3. Gynecomastia
2. Loss of secondary sexual characters (sparse pubic and axillary hair) 4. Spider nevus/ angioma
Hepatomegaly
Hypertension: Portal Hypertension ONLY when CIRRHOTIC stage develops
Asymptomatic!! OR ≥ 1 of the followings Pathophysiological changes clinical features
Ascites‐ Abdominal swelling Elevated portal venous A Ascites
hydrostatic pressure
Bleeding varices: Hematemesis and/or Melena
Opening up of portocaval B Bleeding varices GI
Collaterals‐ Visible over abdominal wall with direction of (Portosystemic) collaterals bleeding/ (at gastro-
filling “away from the umbilicus esophageal junction)

Caput medusae: collateral at periumbilical region C Collaterals- Visible over

Congestive splenomegaly abdominal wall with
direction of filling “away
Disease related features from the umbilicus”
Encephalopathy: Portosystemic encephalopathy Caput medusa- collaterals
surrounding umbilicus
Fetor hepaticus sweetish/ ammoniacal smell in the breath Portal venous congestion  C Congestive splenomegaly
due to presence of mercaptan Splenic venous congestion
Gastropathy: non‐specific abdominal symptoms D Disease- f/o underlying
disease responsible for P.
Hypersplenism: Splenomegaly with pancytopenia due to Htn
peripheral destruction of blood cells due to hyperactive Toxic products bypass the E Encephalopathy-
reticuloendothelial [RE] cells of spleen liver and reach systemic Portocaval
circulation through encephalopathy
Liver failure: conventionally this term is used when Portosystemic collateral
1.Detoxifying function fails F Lung: Fetor hepaticus
And/or Splanchnic congestion G Congestive gastropathy
2.Synthetic function fails

Liver disease patients

Pre/Non cirrhotic stage Cirrhotic stage
Clinico-investigation picture

Manifestation(s)/ Evidence(s) of liver damage Manifestation(s)/ Evidence(s) of liver damage

NO evidence of Portal Hypertension +++
evidence of Portal Hypertension

Investigations
1. Blood:
CBC, CRP
Na+ K+ Urea Creatinine
LFT: (detailed Discussion on LFT in “general” volume)
 Biochemical markers of HEPATO-BILIARY DISEASE: Bilirubin, Enzymes
 Synthetic function markers: Bilirubin & liver enzymes tell us it’s a
1. Serum Albumin level DISEASED LIVER Albumin/clotting profile/
2. Coagulation profile: PT, INR (Extrinsic), aPTT (intrinsic) Ammonia tell us HOW BAD is the diseased liver
 Detoxificating function marker: Serum Ammonia level
Disease/Etiology identifying/confirming blood tests
2. Imaging:
USG abdomen:
 Abnormal appearance of Liver helps helps to diagnose liver disease & it’s stage
 Biliary disease & it’s cause
 Shows many of the effects of Liver disease: Portal hypertension, ascites, Hepatosplenomegaly
CT/ MRI of Liver
MRCP: for Pancreato‐biliary disease

3. Upper GI Endoscopy: MUST!! If Portal hypertension (hence Cirrhosis) is suspected‐ to look for Varices
4. Liver biopsy/FNAC

Treatment of Hepatocellular failure

Supportive: Definitive:
Treatment for:
a. Ascites
b. Bleeding (or even non bleeding)varices
c. Coagulopathy
d. xx Etiology: Treat/ Remove
e. Encephalopathy End stage Liver failure: Liver transplantation
f. xx
g. Gastropathy
h. Hepato‐pulmonary/ Hepato‐renal syndrome
Portocaval collaterals
Anastomotic vessels which open up between portal and systemic circulation in a patient of portal hypertension.
Effects:
Beneficial Harmful
Reduction of portal hypertension Rupture of collateral at gastro‐esophageal region, leading to GI bleed
Toxic nitrogenous products bypass the liver & enter systemic circulation
leading to ● Portosystemic encephalopathy
● Fetor hepaticus
Sites: many but clinically relevant sites are: 1. Gastro‐esophageal region (Varices) 2. Superficial abdominal wall

Clinical features:
1. GI bleed:
 Hematemesis and/or Melena
 Hemodynamic instability
2. Visible collaterals:
Superficial abdominal venous prominence ± Caput
Direction of filling: Away from the umbilicus
3. Portosystemic shunting through collaterals:
 Portosystemic encephalopathy
 Fetor hepaticus.

Investigations: Same as portal hypertension

Treatment:
Supportive treatment
A.Airway:
To be protected: Intubation particularly if there is risk of aspiration
If required: Oropharyngeal suction
B. Breathing: Oxygen
C. Circulation:
IV fluid resuscitation (Preferred fluid of choice: Normal saline)
In case of severe bleeding: Blood transfusion
Coagulopathy (platelet, vitamin K, fresh frozen plasma).
D. Drugs: Reduces bleeding by splanchnic vasoconstriction:
 Vasopressin analogue: Terlipressin
 Somatostatin analogue: Octreotide
Definitive treatment
E. Endoscopy with Endoscopic Interventional treatment: Endoscopy confirms the presence of varices and
subsequently they can be treated endoscopically by the 2 following methods: both of which stop bleeding by variceal
“destruction”
 Endoscopic Variceal ligation (banding) {EVL}
 Endoscopic Injection sclerotherapy: Intra and para‐variceal administration of sclerosing agents:
o Ethanolamine oleate
o Sodium tetradecyl sulfate
F: Endoscopy not Feasible: this is highly unrealistic in today’s world
 Balloon tamponade of varices by Sengstaken-Blackmore tube:
F: Future bleeding prevention:
 Endoscopy‐ Surveillance Endoscopy with EVL/Sclerotherapy to achieve Eradication of varices
 Medical prophylaxis‐ Nonselective β blocker: Propranolol
(Propranolol reduces portal pressure by causing splanchnic vasoconstriction and by reducing cardiac output)
F: Failure of all the above definitive treatment: Transjugular intrahepatic portosystemic shunting (TIPS)
F: Final option: Liver transplantation (Shunt is created to DIVERT more blood from portal to systemic circulation)
So, variceal blood flow reduces BUT TIPS increases the risk of Encephalopathy
Ascites
Accumulation of free fluid in the peritoneal cavity.
Causes of ascites:
1. Ascites as part of anasarca: “systemic defect” 2. Ascites without anasarca: “local defect”
a. Cirrhosis a. Malignancy: Can be ANY malignancy with
b. CCF‐Right heart failure Peritoneal involvement BUT commonly….
c. Chronic kidney disease  GI malignancies
d. Constrictive pericarditis  Gynaecological malignancies
e. Nephrotic syndrome b. Peritoneal Infection
Theoretically this group of pts should develop “fluid  TB
accumulation” everywhere BUT practically they  Non Tubercular
develop “fluid accumulation” in ≥ 1 the potential c. Acute pancreatitis
areas, so they can come with fluid in any 1 area or
fluid in multiple areas.
Of all these diseases ASCITES is the “mode of presentation” typically in
So Ascites DOESNOT mean 1. Chronic Liver disease
But that DOESNOT mean these 3 types
it’s a case of Cirrhosis!!!! 2. Malignant Ascites of patients will ALWAYS present with
3. Peritoneal Infection: TB/ Non-TB ascites ascites!!
 Causes/ mechanism of ASCITES in Cirrhosis
If you are a doctor!! If you are a “Final MB”
………………
Principal factor is Portal Hypertension which leads
to a series of local and systemic events, all of which
contribute to develop ascites
An additional factor is Hypoalbuminemia (due to
Hepatocellular dysfunction) which by reducing
COT/COP contribute to develop ascites
Principal factor “>> “powerful” additional factor
So in a Liver disease patient ……………….
Ascites typically develops in Cirrhotics
“I repeat (again)………………………………………..
that doesn’t mean ALL Cirrhotics will have Ascites”

Factors Aggravating ascites in cirhhosis:

Adherence: Nonadherence to treatment: particularly Noncompliance to diuretic and diet ( salt & fluid restriction)
Bacterial Peritonitis: Spontaneous bacterial peritonitis (SBP)
Carcinoma: Development of Hepatocellular Ca which some of the cirrhotics develop “silently”
D: Disease progression
Clinical features: In a patient of Ascites there will be OFTEN( not always!!) 2 sets of symptoms & signs
1. Those due to ascites
2. Those due to the underlying cause
Symptoms: Asymptomatic till ascites is insignificant! OR ≥ 1 of the followings
Abdominal swelling: Progression will vary according to the rate & amount of fluid accumulation
Abdominal discomfort/heaviness: severity will vary according to the rate & amount of fluid accumulation
Body weight gain
Breathlessness: ONLY in patients with MASSIVE ascites: due to “mechanical effect”
Cause related symptoms: ‘Diseases causing ascites’ will also produce ‘other symptoms’ which help us to predict the
provisional cause of ascites BUT in some patients these ‘other symptoms’ are absent‐ this may happen with any of the
disease. So, an ascitic patient will NOT ALWAYS have “cause related symptoms”
Signs
1. Due to ascites: Shifting dullness For “Final MB”s!!: 2. Flanks: full 3. Fluid thrill 4. Puddle
2. Signs of underlying diseases: If & when present help to predict the provisional cause
(same as “Cause related symptoms”)
Therefore, after assessing a patient with Ascites

Scenario 1 Scenario 2
Cause can be predicted Cause can NOT be predicted
Provisional diagnosis achieved No clear provisional diagnosis…BUT
MOST of the time a doctor will have differential diagnosis

Liver disease Malignancy Infection Occult Liver disease

Occult Malignancy
Occult infection: TB or Non-TB ascites
Investigation: Aim is to diagnose the disease responsible for ascites
1. Blood: Hb, TC, DC, CRP
2. Renal function: Na+ K+ Urea Creatinine (because CKD may be a cause)
3. Liver function test (because CLD may be a cause)
4. Urine analysis (because nephrotic may be a cause)
5. NT Pro BNP/BNP(because CCF may be a cause)
6. CXR (because malignancy may be a cause)
7. USG: may give vital clue of the underlying disease like
 Cirrhosis
 Suspected Intra‐abdominal malignancy

8. Ascitic Fluid aspiration: Often the nature of the fluid gives vital clue of the underlying disease:
Physical appearance:
 Turbid: SBP
 Hemorrhagic: Most of the time it’s Malignancy; but rarely in TB as well
Biochemistry:
 Serum Ascitic Albumin Gradient (SAAG): >1.1 gm/dL: Suggestive of portal hypertension
 High Adenosine Deaminase (ADA): Suggestive of TB
Cytology:
 WBC count:
 Neutrophilic leukocytosis: Suggestive of SBP
 Lymphocytic leukocytosis: Suggestive of TB/ Malignancy
 Atypical cells/Abnormal cell: Malignancy

Microbiology:
 Gram stain
 AFB staining + Mycobacterial culture
Special tests: GeneXpert TB: To detect M.tb DNA
“Not for Final MBs!!...only for Doctors” as this part is NOT important for exam
Further investigations: Fluid analysis may not be conclusive or even if conclusive the underlying disease often will
need further investigations to confirm the exact nature
CT Chest‐ abdomen/PET CT whole body:
 to look for a (radiologically) SUSPECTED malignancy
 to look for a (radiologically) SUSPECTED infection‐ TB
Biopsy/FNAC: from the suspected lesion
 To confirm Malignancy
 To confirm TB/ infection
Endoscopy: If ascites is suspected to be due to cirrhosis/ portal hypertension, to look for varices
Treatment of ascites
1. Diet (fluid and salt restriction)
2. Diuretic: Useful ONLY if ascites is due to “volume overload”= causes where there is a “systemic defect”
a. Spironolactone: K+ sparing diuretic; having side effects of dehydration, hyponatremia, hyperkalemia and painful
gynecomastia
b. Furosemide: loop diuretic; having side effects of dehydration, hyponatremia and hypokalemia.
3. Daily (means regularly) monitoring of the following parameters:
a. Body weight c. Fluid intake and output
b. Abdominal girth
4. Drain (Therapeutic abdominal paracentesis):
 Indication:
a. Significant ascites (symptomatic)
b. Ascites refractory to diuretics
c. If required, even 5‐6 L fluid may be drained in a single sitting.
5. Treat the underlying Disease
Hepatic encephalopathy
Neuropsychiatric syndrome due to cerebral dysfunction due to hepatocellular failure and/or portal hypertension.
Pathogenesis
Underlying/Fundamental defect:
1. Hepatocellular failure: Toxic nitrogenous products and other toxins can’t get detoxified in the liver, so they reach
systemic circulation and then go to brain causing encephalopathy.
2. Portal hypertension: Due to portosystemic collaterals, toxins bypass the liver and reach systemic circulation and go to
Brain‐ after reaching the brain they cause cerebral dysfunction, leading to encephalopathy.
Toxins responsible for hepatic encephalopathy:
A. Ammonia
M. Mercaptan
M. Manganese
O. Octopamine
N. Benzodiazepine
I. Inhibitory neurotransmitters (GABA)
A. Fatty acids
Aggravating/ precipitating factors: These worsen encephalopathy in a person who have “fundamental” defect(s)
1. Conditions which cause ↑↑ NH3 production in intestine:
Increased intestinal protein load
 High dietary protein intake
 GI bleeding
Aggravating factors are CLINICALLY VERY RELEVANT: they are preventable/treatable
 Constipation
Metabolic alkalosis (which may occur in hypokalemia: Here conversion of NH3 to NH4+ is hampered
2. Hepatotoxins:
 Alcohol
 Hepatotoxic drugs
3. Infection
Clinical features
Symptoms & Signs
Altered sensorium
Behavioral change
Confusion/ Coma/Convulsion ++ ↓GCS
Delirium, disturbed sleep rhythm (reversal of sleep‐wake cycle), disturbed mood
Flapping tremor
Focal neurological signs:
a.Apraxia: Inability to perform a skillful voluntary activity which needs precision in spite of normal motor, sensory &
cerebellar function
Constructional apraxia: Tested by
 Inability to draw a 5 pointed star
 When asked to join 20 numbered points by a line, the patient either takes too much time or unable to do it
b.Jerks: Usually normal, however in deep coma: hypo/areflexia may occur
c.Plantar: Normal, however in deep coma: plantar may be bilateral extensor/ absent
Investigation: (basically investigating a “Liver patient”)
1. Blood: Hb, TC, DC, CRP/ESR
2. Renal function: Na+ K+ Urea Creatinine
3. LFT + PT+INR+APPTT
4. NH3 level: ↑ (Ideally Arterial NH3, inreality often venous NH3 ic measured)
5. Arterial blood gas: To assess acid base equilibrium
6. USG abdomen
7. Upper GI endoscopy (to look for any varices)
8. Diagnostic ascitic fluid tap and analysis (if pt has ascites)
9. CT head: To look for any “cerebral” disease particularly the cause of encephalopathy is not clear

Treatment: ≥ 1 of the flowing depending on the clinical scenario

Airway: To be protected, if in deep coma
Aggravating factors: treat/prevention strategy
Breathing: Oxygen and if required Ventilation, if in deep coma
Aviod hepatoxins: Alcohol/hepatotoxic drugs
Bed sore prevention: Back care‐ during the period of immobility
Bleed: if any GI bleed‐ promptly treat
Circulation: IV fluid: to maintain fluid and electrolyte balance
Constipation: MUST be avoided
Capillary blood glucose monitoring: as rick of Hypoglycemia
Lactulose/Lactilol
Catheter: to monitor output
 Orally/Ryles tube
Diet: NPM and R/T feeding till very drowsy/comatose
 Enema
DVT prophylaxis: during the period of immobility
Diet: Protein restricted
Encephalopthy: recurrent/ End stage liver disease
Electrolyte imbalance: to be avoided/ treated
 Consider Liver transplant
Fever: = INFECTION‐ prompt treatment
Role of lactulose in hepatic encephalopathy Gut cleansing agent: Rifaximin
1. Being a non‐absorbable disaccharide, it gets metabolized in the gut, to form H+ which converts toxic NH3 to
nontoxic NH4+.
2. It directly acts on ammonia forming colonic flora and reduces their load.
3. It also acts as a laxative.

Spontaneous bacterial peritonitis (SBP)

Bacterial infection of ascitic fluid, in absence of any intra‐abdominal focus of infection.
Risk factors:
Any patient with ascites are at risk of SBP, however, chronic liver disease/ cirrhotic patients, particularly those with
ascitic fluid albumin level <1gm/dL are at greater risk as they and hence their ascetic fluid is often deficient in opsonins
(Opsonins: subsets of complement components and immunoglobulins who play important role in immune mechanism)

Pathogens: Organisms enter ascitic fluid either by translocation across the gut wall/ through intestinal lymphatics.
Clinical features: 1. Blood: CBC, ESR/ CRP
1. Fever 2. Blood culture sensitivity
2. Pain abdomen 3. Ascitic fluid: diagnostic criteria of SBP
3. Aggravation of ascites a. Cell count: Polymorph. >250/mm3
4. Hepatic encephalopathy may get precipitated AND/OR
5. Tenderness ± signs of peritonitis are usually absent. b. Gram stain + culture sensitivity
Investigation:
Treatment: Treatment of SBP
Established case of SBP‐ 1⁰/2⁰ prevention in high risk patients- recommended
IV Ceftriaxone ± Metronidazole by SOME authorities
• To be changed to proper oral form after few days Long term antibiotic prophylaxis
• Total duration of antibiotic therapy: 7‐10 days  Ciprofloxacin/ Norfloxacin
 Hepatopulmonary syndrome (HPS)
A complication of Liver disease charaterised by pulmonary gas exchange abnormalities leading to arterial
deoxygenation, and evidence of intrapulmonary vascular dilatations
Pathogenesis: of HPS still remains unclear!!.
The hallmark of HPS is microvascular dilatation within the pulmonary arterial circulation. attributable to inadequate
synthesis or metabolism of pulmonary vasoactive substances ( most likely Nitric Oxide) by a damaged liver.
Microvascular dilatation impairs ventilation‐perfusion matching and can produce anatomical and functional shunt
physiology, leading to hypoxemia.

Clinical features:
Symptom: Breathlessness: becomes more prominent when the patient is in standing position (Platypnea)
Signs: SpO2 saturation low‐ falls further when the patient is in standing position (Orthodeoxia)

Investigation
1. Arterial blood gas (ABG)
2. Chest X Ray (CXR): To rule out ANY OTHER focal lung lesion
3. ECG and Echocardiogram: To rule out any cardiac abnormality
4. Echocardiogram with IV saline agitated microbubble (Need to know this if you consider yourself DM before becoming MBBS!!)
Under normal circumstances these microbubbles are trapped in the pulmonary vasculature and absorbed. However in
the presence of Intrapulmonary shunt( as in these patients) or Intracardiac right to left shunts, these microbubbles are
seen in the left heart very quickly.
Treatment: 1.Oxygen 2. Ventilation 3. Liver transplantation
Hepatorenal syndrome (HRS)
A state of renal dysfunction occurring as a consequence of CLD.
Diagnostic criteria:
1. Presence of azotemia: Creatinine↑
2. No other causes of kidney dysfunction
3. No improvement of renal function even after withholding diuretic therapy for 48 hours.
Pathogenesis:
 Due to CLD, there is impaired synthesis/ metabolism of vasodilators, leading to intense renal vasoconstriction;
leading to reduced renal blood flow.
 There is altered hemodynamics but no structural damage to kidneys.
Clinical features:
1. Oliguria/ anuria
2. Features of uremic encephalopathy (due to accumulation of toxins in blood)
Investigations: Renal function test: Na+ K+ Urea Creatinine: Urea, creatinine: ↑
Treatment:
1. Combination of medical agents: Midodrine/Vasopressin/ Terlipressin/Norepinephrine/Somatostatin/ Octreotide
2. Liver transplantation
Coagulopathy
Cause: Impaired synthesis of coagulation factors due to deranged hepatic function.
Clinical features: 1 of the followings
1. Asymptomatic
2. Bleeding manifestation:
External: Gum bleeding, epistaxis, ecchymosis
Internal: Intracerebral hemorrhage, GI bleed, GU bleed.
3. Circulatory crisis: If blood loss is significant, patient may become hemodynamically unstable.
Investigation: Coagulation profile
1. BT/ CT/ Platelet count
2. PT, INR (Extrinsic pathway) ↑
3. aPTT (Intrinsic pathway) ↑
- Often only PT/INR is elevated in CLD as factor VII is the first factor to get depleted.
Treatment:
1. Fresh frozen plasma transfusion, only when there is active bleeding/ before invasive procedure
2. Although it is very commonly used, vitamin K has no role, unless coexistent vitamin K deficiency is suspected
Congestive splenomegaly
It is a common complication of portal hypertension where portal and splanchnic venous congestion leads to passive
congestion in the spleen and finally, splenomegaly.
Hypersplenism
It can occur in a patient with long standing portal hypertension and defined as the combined presence of the following:
1. Splenomegaly
2. Pancytopenia (which gets corrected after splenectomy)
3. Bone marrow hyperplasia..
Congestive Gastropathy/ Portal Hypertensive Gastropathy
Pathogenesis:

Clinical features: Asymptomatic or of the followings

4. Abdominal pain: epigastric discomfort ± pain
5. Bleeding: Overt (Melaena and /or Hematemesis) OR Occult
Diagnosis: Endoscopy shows gastric mucosal congestion and hyperemia.
Treatment: Endoscopic Interventional treatment: Argon Plasma coagulation

“Individual” Liver diseases..underdstanding them as well as the “notes”

Etiology/ cause of Liver disease
ALL SOME of them
Liver involvement/manifestation Extra‐hepatic Involvement/manifestation

Identical irrespective of the etiology Varies according to the etiology

Not mentioned in details as already mentioned before Mentioned

ONLY thing to remind……AGAIN!!

Acute liver disease causing etiology Chronic liver disease (CLD) causing etiology

Pre/Non Cirrhotic stage Cirrhotic stage

Manifestation of liver dysfunction Manifestation of liver dysfunction

++
Manifestation of Portal Hypertension
Investigations
Etiology/ cause of Liver disease

Liver related Extra‐hepatic Involvement related Etiology confirming Investigation

Treatment: Liver related Extra‐hepatic Involvement related
Everything “Liver related” has been covered already….So you will see the “heading” only!!!!
 Acute viral hepatitis
Virus Incubation period Mode of transmission Acute hepatitis Fulminant hepatic failure Chronic hepatitis
HAV 15‐45 days Faeco‐oral + + -
HBV 30‐180 Sexual/Parenteral + + ++
HCV 50‐160 Sexual/Parenteral - - ++
HDV 30‐180 Sexual/Parenteral + - -
HEV 15‐60 Faeco‐oral + + (in pregnancy) -

Viral markers
HAV: Anti‐HAV antibody (Anti HAV): IgM Anti HAV (acute) and IgG Anti HAV (acute or remote)
HBV:
HBsAg:
 In most cases, the first viral marker to appear
 Appears very early during acute hepatitis and usually disappear within few months
 If persists 6 months after an episode of acute hepatitis it signifies a carrier/ chronic hepatitis stage
Anti HBs
 Appears after disappearance of HbsAg
 Presence signifies immunity EITHER achieved by vaccine OR a previous episode of acute hepatitis
 Chronic Hepatitis B patients never develop this
Anti-HBc-antibody: 2 types:
 IgM: Rises during acute infection & gets cleared off the serum after few weeks/months
 IgG: Develops during acute period and persists indefinitely
HBeAg: Secretory form of core antigen.
Appears during acute infection- marker of active viral replication. Therefore, its presence suggests high infectivity.
Anti-HBe-antibody: Appears after disappearance of HbeAg
HBV-DNA: Marker of viral replication
Quantification of HBV‐DNA denotes viral load and therefore is monitored during initiation and monitoring of antiviral
treatment response in chronic hepatitis
Chronic Hepatitis B: here it’s
Acute Hepatitis B: Confirmation of
important to know Infectivity &
virus is enough, nothing else is
viral load‐ so these are checked
relevant‐ so only this is checked
HBsAg
HBsAg HBeAg
Anti-HBe-antibody
HBV-DNA

Viral markers S: E: B: C: E: S: C
HBsAg HBeAg HBV‐DNA Anti‐HBc (IgM) Anti‐HBeS Anti‐HBs Anti‐HBc (IgG)
HCV:
Anti‐HCV: Usually appears during acute period: indicates Hep C infection
HCV‐RNA Quantification: Titre signifies viral load and is monitored during antiviral treatment

HDV: The marker is HDV‐RNA

HEV: Anti‐HEV‐antibody (Anti HEV): It is of 2 types: IgM and IgG.

Clinical features of Acute viral hepatitis: It goes through 3 stages
Pre-icteric stage Icteric stage Recovery stage:
(first few days-1week): (end of 1st week-3rd week):
Uncomplicated disease Abdo pain: RUQ pain Symptoms start to subside Symptoms and signs
Anorexia + Nausea +/‐ vomiting Bilirubinemia: Icterus appears gradually disappears
Some of them Hepatomegaly: Soft, tender Hepatomegaly: Soft, tender

Complicated disease ENCEPHALOPATHY & COAGULOPATHY

Fulminant hepatic 2 most important and common complications
failure: Encephalopathy Fetor hepaticus Fetor hepaticus
Some die
within few weeks of onset Glycemic: tendency to fall Glycemic: tendency to fall
of illness
Hepato‐renal/Pulmonary Hepato‐renal/Pulmonary
Investigation
1.Blood: Viral Markers
Hb, TC, DC, CRP/ESR: Leukopenia may be seen a. Anti‐HAV Transaminases VERY HIGH >>500
Renal function test: Na+ K+ Urea Creatinine b. HbsAg Think of 3I
Liver function test: c. Anti‐HCV Infective Hepatitis
 Bilirubin (Unconjugated and conjugated): ↑↑ d. Anti HEV Iatrogenic: Acute Drug induced Hepats
 Transaminases: ALT, AST: ↑↑↑ (often >1000 U/L)
 GGT/ ALP: ↑ (mild to moderate rise in level) Ischemic: Acute Ischemic Liver injury
 Albumin: normal/ ↓; PT, INR, aPTT: normal/ ↑
Falling albumin level and coagulation abnormalities are warning signals of a possible impending hepatic failure
2.USG abdomen
Treatment: Level of treatment MAINLY DEPENDS ON WHETHER ENCEPHALOPATHIC OR NOT
≥ 1 of the following
Absolute bed rest: till transaminase level STARTS to come down/ patient becomes asymptomatic
Admit:
 If (even if mild) manifestation of Encephalopathy
 If poor oral intake
Basic investigations: periodically Monitor INR & Albumin…(“kolkattayia style daily Bili/SGOT/SGPT is NOT required”!!)
Circulation: IV fluid if oral intake is inadequate: Dextrose
Diet: Normal palatable diet, restrict protein IF encephalopathy
Drugs:
N-Acetylcysteine: Traditionally used for Paracetamol overdose
 Avoid hepatotoxic drugs
Has been recommended for
 Antiemetic “Non- Paracetamol” Acute Fulminant Hepatic failure
Encephalopathy: Look for early signs of
Fulminant Hepatic failure‐ Encephalopathic patient: ≥ 1 of these
Aggravating factors: treat/prevention
 Airway: To be protected, if in deep coma
Aviod hepatoxins: Alcohol/hepatotoxic drug
 Breathing: Oxygen and if required Ventilation, if in deep coma
Bleed: if any GI bleed‐ promptly treat
 Bed sore prevention: Back care‐ during the period of immobility
Constipation: MUST be avoided
 Circulation: IV fluid: to maintain fluid and electrolyte balance
Lactulose/Lactilol
 Capillary blood glucose monitoring: as rick of Hypoglycemia
 Orally/Ryles tube
 Catheter: to monitor output  Enema
 Diet: NPM and R/T feeding till very drowsy/comatose Diet: Protein restricted
 Drug: N‐Acetylcysteine Electrolyte imbalance: to be avoided/ treated
 DVT prophylaxis: during the period of immobility Fever = INFECTION‐ prompt treatment
 Encephalopthy: Refractory to medical therapy‐ Liver transplant Gut cleansing agent: Rifaximin
Complications: Fulminant hepatic failure
 Alcoholic liver disease
Risk factors:
1. Alcohol related: men > 40 g, particularly > 80 g/day for > 10 yrs (Women: Half of this amount)
2. Non-alcohol related: a. Malnutrition b. Gender: Females risk > males c. Coexisting liver disease of another type
Clinical features:
Pre/Non Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
++
 Asymptomatic OR ≥ 1 manifestation of Portal Hypertension
Clinical “Stigma”/Evidence of chronic alcohol excess:
For a doctor For a “ Final MB”
1. History of “significant alcohol consumption” Haptic facies: Wasted face with+ muddy discolouration
2. History of “significant alcohol consumption” Bilateral parotid swelling
3. History of “significant alcohol consumption” Dupuytren’s contracture: Fibrotic thickening of palmar
4. History of “significant alcohol consumption” fascia leading to fixed flexion deformity & limited
5. History of “significant alcohol consumption” extension of ring and little finger
6. History of “significant alcohol consumption” Hyperestrogenemic manifestations: More prominent than
10000!!: History of “significant alcohol consumption” in other causes of CLD
Investigation
1. Blood:
a.CBC, ESR/ CRP
 Hb: ↓ in case of GI bleed TC, DC, Platelet: Cytopenia: Due to marrow toxicity of chronic excessive alcohol
 ↑MCV: Due to coexisting folic acid deficiency( which is often present in alcoholics)
b. Renal function test: Na+ K+ Urea Creatinine: Urea‐creatinine level may be ↓ due to low catabolic state.
c.LFT:
 Bilirubin: May be ↑
 ALT, AST: Mild to moderate ↑, usually don’t exceed 300 U/L
 Typically OFTEN (due to alcohol induced inhibition of pyridoxal phosphate, a coenzyme of ALT)
 GGT, ALP: Mild to moderate ↑ (markers of cholestasis)
 Albumin: Normal/ ↑ PT, aPTT, INR: Normal/ ↑
2. USG abdomen: May show (depending on the stage)
a. Fatty liver b. Hepatomegaly c. Cirrhotic look d. Evidence of portal hypertension‐ Ascites/Splenomegaly
3. Upper GI endoscopy: To look for varices
4. Fibroscan
Treatment of alcoholic liver disease
Supportive: Complication directed treatment Definitive:
Treatment for: Etiology: Treat/ Remove
Ascites Alcohol Abstinence:
Bleeding (or even non bleeding) varices Acute withdrawal syndrome: If required, drug to control it
Coagulopathy Chlordiazepoxide/ Diazepam/Acamprosate
D xx B vitamin supplementation partcularly Thiamine
Encephalopathy as alcoholics are often deficient in B1
F xx Corticosteroid: Prednisolone for 4 weeks
Gastropathy
Hepato‐pulmonary/ Hepato‐renal syndrome End stage Liver failure: Liver transplantation
 Non-alcoholic fatty liver disease (NAFLD)/ Non-alcoholic steatohepatitis (NASH)
Liver disease due to fatty infiltration (in absence of alcohol abuse) with/ without accompanying inflammation.
Risk factors:
1. BMI : High 4. Drugs (Corticosteroid/ Amiodarone)
2. Cholesterol: High 5. Endocrine (Cushing’s syndrome)
3. Diabetes
Pathogenesis: The following factor play important role in NAFLD:
Insulin resistance: It ultimately leads to lipid peroxidation and oxidative damage to the liver
(In Alcoholic liver disease, 2 important factors are: toxic effect of acetaldehyde and toxic effect of TNF)
Clinical features:
Pre/Non Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
++
 Asymptomatic OR ≥ 1 manifestation of Portal Hypertension
Investigation
1. Liver disease related investigations…already covered multiple times (no more wastage of paper!!)
2. Etiology related: Risk factor stratification
 Blood:
Lipid profile
Blood glucose: Fasting and post‐prandial
Treatment
Treatment for NAFLD/NASH
Supportive: Complication directed treatment (see above!!)
Definitive: Etiology: Treat/ Remove
Risk factor modification
 Alcohol Avoid: as simultaneous alcohol may worsen NAFLD
 BMI: if high Body weight rediction
 Cholesterol: if high Hypocholestolemic drug
 DM: strict glycemic control
 Etiology: Treat any other risk factor
End stage Liver failure: Liver transplantation
Haemochromatosis
It is a disorder of iron metabolism characterized by excessive hepatic and extrahepatic iron deposition.
Pathogenesis:
HFE gene: In mutations of this gene, there is ultimately excess intestinal iron absorption.
Hepcidin: A key iron regulatory protein which is not synthetized properly. So, there is excessive hepatic iron deposition
which “spills over” into extrahepatic sites.
Clinical features: “HAEM”
H- Hepatic
Pre/Non Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
++
 Asymptomatic OR ≥ 1 manifestation of Portal Hypertension
H- Heart‐ Cardiomyopathy‐ Cardiac failure/ Conduction disturbances
A-Arthralgia/ Arthritis‐ Commonly affects MCP joints (particularly 2nd and 3rd)
E- Endocrinal glands‐ Pancreas‐ Diabetes; Pituitary‐ Hypogonadism
M- Melanin (brown) + excess iron deposition in skin‐ Slate grey/ Greyish brown‐ Bronzing of skin/ Bronze diabetes

Investigation
To diagnose organ defect: To confirm hemochromatosis:
Liver: “Liver related investigations” Iron study: Serum iron: ↑↑ Serum ferritin: ↑↑
DM: Fasting and post‐prandial Liver biopsy with estimation of hepatic iron index
Heart: ECG; Echocardiogram Molecular testing: Detection of C282Y mutation
Treatment
1. Supportive treatment: For organ complications
2. Treatment of iron deposition: 1. Regular phlebotomy 2. Iron chelators: Desferrioxamine/Deferriprone

Wilson’s disease (HepatoLenticular Degeneration)

It is a disorder of copper metabolism characterized by excessive hepatic and extrahepatic copper deposition.
Risk factors: Mutations of the ATP7B gene result in impaired trafficking of copper (decrease in biliary copper excretion)
in and through the hepatocytes which leads to excessive hepatic copper deposition which then “spills over” to different
extra‐hepatic sites.
Clinical features:
H- Hepatic
Pre/Non Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
++
 Asymptomatic OR ≥ 1 manifestation of Portal Hypertension
L- Lentiform nucleus Cu++ deposition‐
● Parkinsonism ● Movement disorder ● Cerebellar degeneration ● Psychiatric manifestation
D- Descemet membrane Cu++ deposition‐Brownish‐yellow ring‐ Best seen by slit lamp= Corneal Kayser-fleischer ring
Investigation
To assess organ damage: To confirm the disease:
“Liver related investigations” ↓ Serum Ceruloplasmin
MRI brain ↑ Free serum copper, but ↓ total serum copper
↑ 24 hours Urine copper excretion
Liver biopsy: if other tests are inconclusive
 High Hepatic copper concentration
Screen family members for mutation if diagnosis is
confirmed.
Treatment
Supportive: Complication directed treatment (see above!!)
 Treatment for Liver disease
 Treatment for Neuropsychiatric manifestation
Definitive:
Etiology: Treat/ Remove
 Cu++ chelating agent: D‐Penicillamine‐ If fails/ patient can't tolerate‐ Triamtene
 Reduction of Cu++ absorption from intestine: Zinc
End stage Liver failure: Liver transplantation
 Primary biliary cirrhosis (PBC)
Autoantibody mediated by inflammation and subsequent fibrotic obliteration of intrahepatic biliary canaliculi.
Pathogenesis: Antibodies against Pyruvate dehydrogenase complex of canalicular cell mitochondria (Anti‐
mitochondria antiantibody) ‐ Intrahepatic cholestasis ‐ Canalicular inflammation and fibrosis ‐ Eventually liver disease
Clinical features:
P: Pigmentation
B: ↑Bile acid: Pruritus
C:
Cholestasis Fat malabsorption- Steatorrhea/ Flatulence
Vit A, D, E, K malabsorption: A- Night blindness D‐Musculoskeletal pain K‐ Coagulopathy
Conjugated hyperbilirubinemia‐ Icterus
Chronic liver disease
Pre/Non Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
++
 Asymptomatic OR ≥ 1 manifestation of Portal Hypertension
Clubbing
Cholesterol: Hypercholesterolemia: Xanthelesma Xanthomata
Investigations:
1. “Liver related investigations” 2. To confirm the disease: Serum anti‐mitochondrial antibody(AMA)

Treatment:
1. Symptomatic: 2. Treatment of chronic liver disease
 Cholestasis: Ursodeoxycholic acid (UDCA)
 Pruritus: Cholestyramine (Bile acid binding agent)
 Vitamin supplementation (if required)
Autoimmune Hepatitis (AH”)
Autoantibody mediated inflammation of liver which may lead to acute hepatitis as well as chronic liver disease.
Clinical features:
Age‐ young females Association: Other Autoimmune disorders‐ Sjogren’s syndrome, autoimmune thyroiditis
Amenorrhea: Often occurs in these patients
Hepatic‐ Acute hepatitis ± fulminant hepatic failure or Chronic Hepatitis
Pre/Non Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
++
 Asymptomatic OR ≥ 1 manifestation of Portal Hypertension
Investigations:
1. “Liver related investigations”
2. To confirm the disease: Serum Autoantibodies:
 Type 1 AH: Anti‐soluble liver antibody (ASLA); ANA
 Type 2 AH: Anti‐liver kidney microsomal antibody type 1 (ALKM1)
Treatment Supportive:
 Treatment for Liver disease (see above!!)
 Definitive: Corticosteroid + Azathioprine OR Mycophenolate mofetil
 Liver abscess
2 TYPES: Amebic and Pyogenic
Pathogenesis:
Amebic: Trophozoite of Entamoeba histolytica- Organism enters by faeco-oral route - Cyst/ vegetative form in the intestine -
Trophozoite in the liver- Abscess formation
Pyogenic: Portal of entry:
1. Through portal vein: Pylephlebitis (infection of portal vein)
2. Through CBD: Ascending cholangitis
3. Through hepatic artery: Bacteremia
Clinical features: SAME for both
Constitutional symptoms: Focal: May not be present
Fever RUQ discomfort
++ ≥ 1 of these On examination:
Appetite loss 1. RUQ tenderness: On percussion, tenderness over
Body weakness; Bodyache right lower intercostal spaces noted
Chill (+/‐ rigor) 2. Hepatomegaly may be present.
Drowsiness
Energy lack

Investigation SAME for both

Blood: Hb, TC, DC, ESR/CRP
Blood C/S
LFT: Nonspecifically mildly deranged
USG abdomen/CT abdomen: Usually confirms abscess (Abscess is a RADIOLOGICAL diagnosis!!)
Aspiration of Pus: Microbilogical tests of the pus

Treatment
Empirically IV Ceftriaxone + Metronidazole To be changed to appropriate oral forms once patient starts to
improveTotal duration: Approx. 3 weeks.
Hepatocellular carcinoma (HCC)
Primary malignancy of liver. Remember!!...general discussion on “Malignancy”
Risk factors:
 Chronic hepatitis infection PARTICULARLY chronic HCV, also chronic HBV
 Cirrhosis (of any etiology) itself is an independent risk factor
Clinical features: Asymptomatic OR ≥ of the following
Constitutional:
Appetite loss
Body weight loss
Cachexia
D xx
Energy lack
Fever: “disease/malignancy fever”)
Loco-regional: Liver related…ABCDEFGH….
(Portal hypertension is present in some of these of patients as they may have a background of Cirrhosis)
Metastatic: Bone/Brain/Peritoneal (ascites)/Lung Involvement
Investigation
To confirm malignancy: Cytology/Histopathology: FNAC/Biopsy: Radiologically guided Liver biopsy/FNAC
To know the spread: Radioimaging (also gives the 1st clue of the diagnosis)
 Contrast CT‐ brain+ thorax + abdomen
 Contrast MRI‐ brain+ thorax + abdomen
 PET‐ CT whole body
 Isotope bone scan‐ specially for Bone mets
Overall physical assessment: CBC +LFT + KFT + Ca + ECG + Echo + PFT
Tumor Marker: Serum AFP (α‐fetoprotein): Significantly high
Treatment
Treatment of HCC
depending on the scenario
Disease directed treatment Palliative treatment
(Symptoms/complication directed treatment)
Based on these Medical /Surgical therapy
1. Exact histopatholgical Type 4. Age
2. Stage of the malignancy 5. Financial factor
3. Comorbidities/Level of fitness 6. Response to any treatment already offered

Curative intention Disease downsizing/downgrading intention

(aim is to make disease free) (aim is to decrease disease burden)

Treatment options
● Surgery and/or ● Oncomedicine and/or ● Radiotherapy

Tumor resection Liver transplantation TACE Systemic Radiofrequency ablation of tumor

TransArterial ChemoEmbolisation
TACE: Local delivery of chemotherapy with a procedure called embolization to treat cancer, most often of the liver. It is a
non‐surgical and minimally invasive procedure performed usually by an interventional radiologist.
Budd Chiari syndrome
Thrombosis of the hepatic vein
Causes:
Hypercoagulable state/ disorders:
 Anti‐phospholipid antibody syndrome
 Nephrotic syndrome
 Protein C/ protein S/ antithrombin 3 deficiency
Idiopathic
Clinical features:
1. Sudden RUQ pain 3. Patient may develop fulminant hepatic failure
2. Tender soft hepatomegaly 4. Ascites.
Investigation
1. USG abdomen with Doppler study
2. CECT abdomen
3. Coagulation studies
Treatment: Anticoagulation
 Wernicke Korsakoff Syndrome
It is a neurodegenerative complication of vitamin B1 deficiency, most commonly seen in chronic alcohol abusers.

Pathogenesis:
Degeneration of different areas of brain: mammillary body/ thalamus/ median temporal lobe/ cerebellum. Chronic
alcohol abuse interferes with absorption and metabolism of thiamine, often leading to severe thiamine deficiency.

Clinical features: WKS has two components: 1. Wernicke’s encephalopathy 2.Korsakoff psychosis
Wernicke’s encephalopathy: Usually these symptoms are reversible with thiamine replacement therapy
1. Ataxia
2. Ophthalmoplegia
3. Confusion
Korsakoff’s psychosis: Irreversible
1. Cognitive symptoms: Insomnia, Anxiety, Difficulties in concentration, Loss of memory for the immediate past, and
gradual degeneration of mental state
2. Confabulation: Incorrect memories that the patient holds to be true, and may act on, arising spontaneously without
any provocation. (In viva table we all “confabulate”only difference is there is a provocation!!)
3. Patient may have features of Wernicke’s encephalopathy
Investigation 1. MRI of brain: may show some “suggestive” changes 2. Vitamin B1 estimation
Treatment
1. Prevention: For ALL chronic alcoholic‐ must receive high dose thiamine
In patients with H/O significant alcohol abuse till recently, IF such a patient requires IV dextrose containing fluid, must receive
high dose thiamine before/ at least along with the fluid. (glucose oxidation is a thiamine consuming process and therefore,
may unmask any underlying deficiency and may precipitate Wernicke Korsakoff syndrome)
2. Established cases: High dose thiamine replacement.

Child-Pugh Score for chronic liver disease/ cirrhosis…….(”For Short Note obsessed”)
Points/Score 1 2 3
Ascites None Mild‐ moderate Severe
(diuretic responsive) (diuretic refractory)
Encephalopathy None Mild‐ moderate Severe
Albumin (gm/dL) >3.5 2.8‐3.5 <2.8
Bilirubin (mg/dL) <2 2‐3 >3
INR <1.7 1.7‐2.3 >2.3
Interpretation
Total score 5‐6 7‐9 10‐15
Prognosis Least severe Liver disease Moderately severe LD Most severe LD
 Cirrhosis……
Nothing new!!!...Basically “summary” of last few pages as we have already read EVERYTHING aboutit
It is a condition characterized by:
 Clinically by: Hepatocellular dysfunction + Portal hypertension
 Histopathologically by: Hepatic fibrosis + Necrosis + Regenerative nodules (pseudo‐lobules) + Architectural
destruction of liver.
Causes: ABCDE of chronic liver disease

Clinical features: ABCDEFGH including Portal Hypertension of liver disease

Disease related features
Alcoholic Cirrhosis: History….history….& history!!
Chronic Hepatits B/C: History..patient says “ I have hep B/C”!!! (A doctor who claims to diagnose B/C clinically is “a bc”)
Primary biliary cirrhosis (PBC):
 Clubbing Underlying diseases/causes
 Pigmentation Don’t expect to diagnose these clinically even the biggest “Cirrhosisologist” doesn’t
Wilson’s disease: MOST of these diseases are diagnosed from investigation results
 Kayser–Fleischer ring therefore from a clinical point of view Causes of chronic liver disease are…..
 Involuntary movements
1.Aloholic Liver disease 2.Rest of them= Non‐Alocholic causes
 Psychiatric manifestation
Hemochromatosis:
 Cardiomyopathy: Heart failure
 “Bronzing” of the skin
NAFLD: presence of risk factors
Investigations
Liver related Etiology related
CBC, CRP
Chronic Hep B: HBsAg/ HBeAg/ Anti-HBe-antibody/ HBV-DNA
Na+ K+ Urea Creatinine Chronic Hep C: Anti HCV/ HCV RNA
LFT: Hemochromatosis:
Bilirubin  Iron study: Serum iron: ↑↑ Serum ferritin: ↑↑
AST, ALT  Liver biopsy with estimation of hepatic iron index
GGT, ALP  Molecular testing: Detection of C282Y mutation
Albumin, PT, aPTT, INR Wilson disease:
NH3 level ↓ Serum Ceruloplasmin
↑ Free serum copper, but ↓ total serum copper
USG abdomen
↑ 24 hours Urine copper excretion
Upper GI endoscopy: any varices Liver biopsy: High Hepatic copper concentration
Diagnostic ascitic fluid aspiration: Autoimmune Hepatitis: Anti SLA/Anti LKM
 SAAG >1.1. gm/dL
 PMN >250: suggestive of SBP
Treatment of chronic liver disease
1. Treatment of complications:
Disease/Etiology related treatment
Ascites:
Alocholic Cirrhosis: STOP it!!
 Dietary Na+ and water restriction
(Not that Others will continue heavy drinking!!)
 Diuretics (Loop diuretics/ K+ sparing diuretics)
Chronic Hep B/C: Antiviral
 Daily body weight monitoring Biliary Cirrhosis: Symptomatic
 Daily intake‐output chart Drug induced: Stop the offending drug
 Drainage: therapeutic ascitic fluid aspiration Hemochromatosis: Iron chelator
Bleeding varices: Wilson disease: Cu chelator
 Circulation: IV fluid + blood transfusion) NAFLD: Risk factor modification
 Drugs (Terlipressin) AH: Steroid/Azthioprine/Mycophenolate
 Endoscopy
 Endoscopic band ligation
 Sclerotherapy
 Prevention: β‐blocker
Coagulopathy:
 Fresh frozen plasma in case of active bleeding
Encephalopathy:
A. Avoid alcohol/ hepatotoxic drugs End Stage Liver disease
B. Urgently treat any associated GI bleed Transplantation
C. Prevent/ treat constipation ESLD= Medically unmanageable/refractory
D. Dietary protein restriction  Ascites
E. Treat any electrolyte imbalance  Bleeding varices
F. Treat any associated infection  Encephalopathy
G. Gut cleansing agent (Rifaximin)  Hepatorenal
 Hepatopulmonary
Gastropathy: Endoscopic Argon Plasma coagulation
Hepatopulmonary: Ventilation
Hepatorenal: Dialysis
I expect you have realized why did I say “a summary” of previous pages!!!

PS:
CLD in Non-cirrhotic stage overall “synopsis” remains the same….EXCEPT (as discussed NUMEROUS TIMES)
Portal Hypertension part is not applicable