Liver Cirrhosis

Definition

Etiology

1. Alcohol-associated liver disease
2. Chronic viral hepatitis, especially hepatitis B and C
3. Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH)
4. Autoimmune hepatitis
5. Cholestatic diseases such as primary biliary cholangitis and primary sclerosing cholangitis
6. Metabolic and genetic disorders
   • Hemochromatosis
   • Wilson disease
   • Alpha-1 antitrypsin deficiency
7. Drugs, toxins, chronic right-sided heart failure, and cryptogenic causes

Pathogenesis

• Increased resistance to portal blood flow, causing portal hypertension
• Reduced hepatic synthetic function, causing low albumin and prolonged INR
• Impaired detoxification, causing hepatic encephalopathy
• Reduced bile formation and excretion, causing jaundice
• Increased risk of hepatocellular carcinoma (HCC)

Clinical Features

Compensated cirrhosis

• Fatigue, anorexia, weight loss
• Nausea
• Right upper abdominal discomfort
• Hepatomegaly or a small shrunken liver
• Spider angiomas, palmar erythema
• Gynecomastia, testicular atrophy, loss of body hair in men
• Easy bruising

Decompensated cirrhosis

1. Portal hypertension
   • Splenomegaly
   • Thrombocytopenia due to hypersplenism
   • Esophageal or gastric varices
   • Caput medusae
2. Ascites
   • Abdominal distension, pedal edema
   • May become refractory
   • Can lead to spontaneous bacterial peritonitis (SBP)
3. Variceal bleeding
   • Hematemesis, melena, shock
   • A medical emergency
4. Hepatic encephalopathy
   • Sleep disturbance, personality change, confusion
   • Asterixis and coma in severe cases
5. Hepatorenal syndrome
   • Functional acute kidney injury in advanced cirrhosis
6. Hepatocellular carcinoma
   • A major long-term complication

Investigations

Blood tests

• Complete blood count: anemia, leukopenia, thrombocytopenia
• Liver function tests: raised bilirubin, AST, ALT, alkaline phosphatase
• Serum albumin: decreased
• Prothrombin time/INR: prolonged
• Renal function and serum electrolytes
• Viral markers: HBsAg, anti-HCV
• Autoimmune and metabolic work-up where appropriate

Imaging

• Ultrasound with Doppler: nodular liver, splenomegaly, ascites, portal vein changes
• Transient elastography: estimates liver stiffness and fibrosis
• CT or MRI: evaluates complications and suspected HCC

Endoscopy

Ascitic fluid analysis

Liver biopsy

Severity Assessment

Child-Turcotte-Pugh score

• Encephalopathy
• Ascites
• Bilirubin
• Albumin
• Prothrombin time/INR

MELD-Na score

Management

1. Treat the underlying cause

• Complete alcohol abstinence in alcohol-associated cirrhosis
• Antiviral therapy for hepatitis B or C
• Weight reduction, diabetes control, and cardiovascular-risk management in MASLD
• Corticosteroids with or without azathioprine for autoimmune hepatitis when indicated
• Phlebotomy for hemochromatosis
• Chelation therapy for Wilson disease
• Stop hepatotoxic medicines and avoid unnecessary herbal products

2. General measures

• Nutritional assessment and treatment of sarcopenia
• Adequate calorie and protein intake, usually about 1.2-1.5 g protein/kg/day unless a specialist advises otherwise
• Avoid prolonged fasting and consider a late-evening snack
• Avoid alcohol completely
• Avoid nonsteroidal anti-inflammatory drugs because they can precipitate renal failure and gastrointestinal bleeding
• Avoid unnecessary sedatives, especially benzodiazepines
• Vaccinate against hepatitis A and B if nonimmune, and provide routine influenza and pneumococcal vaccination as appropriate
• Review drug doses because hepatic dysfunction alters drug metabolism

3. Management of ascites

• Dietary sodium restriction, generally less than 2 g sodium/day
• Diuretics: spironolactone, often combined with furosemide in a 100 mg:40 mg ratio
• Monitor body weight, renal function, sodium, potassium, and blood pressure
• Large-volume paracentesis for tense or refractory ascites, with albumin replacement when large volumes are removed
• Evaluate refractory ascites for TIPS in selected patients and for transplantation

4. Prevention and treatment of variceal bleeding

• Screen for varices with endoscopy when indicated
• Primary prophylaxis with a nonselective beta blocker, such as carvedilol, propranolol, or nadolol, in suitable patients
• Endoscopic variceal ligation where indicated
• Acute bleeding requires resuscitation, vasoactive therapy such as octreotide or terlipressin, prophylactic antibiotics, and urgent endoscopic band ligation
• TIPS may be necessary for uncontrolled or recurrent bleeding

5. Hepatic encephalopathy

• Identify and correct precipitating factors: infection, gastrointestinal bleeding, constipation, dehydration, electrolyte disturbance, sedatives, and renal failure
• Lactulose is first-line treatment and is titrated to about 2-3 soft stools daily
• Add rifaximin for recurrent episodes despite lactulose
• Avoid unnecessary sedatives

6. Spontaneous bacterial peritonitis

• Suspect in a patient with ascites who develops fever, abdominal pain, encephalopathy, hypotension, or renal dysfunction
• Treat promptly with appropriate intravenous antibiotics, commonly a third-generation cephalosporin depending on local resistance patterns
• Albumin may be given in selected patients to reduce renal complications
• Secondary antibiotic prophylaxis is often required after an SBP episode

7. Hepatorenal syndrome

• Stop nephrotoxic agents and diuretics where appropriate
• Give albumin and treat triggers such as infection or hypovolemia
• Use vasoconstrictor therapy according to local specialist protocol
• Expedite transplant assessment

8. HCC surveillance

9. Liver transplantation

Prognosis

Conclusion

Diabetic Ketoacidosis (DKA)

Definition

1. Hyperglycemia or known diabetes
2. Ketosis
3. Metabolic acidosis

Etiology and precipitating factors

• Omission, inadequate dose, or interruption of insulin therapy
• New-onset diabetes mellitus
• Infection, especially pneumonia, urinary infection, and sepsis
• Myocardial infarction
• Stroke
• Pancreatitis
• Trauma, surgery, or burns
• Pregnancy
• Alcohol or cocaine use
• Drugs such as corticosteroids, thiazide diuretics, sympathomimetics, and atypical antipsychotics
• Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which may cause euglycemic DKA with only mildly elevated glucose

Pathophysiology

• Increased hepatic gluconeogenesis and glycogenolysis, causing hyperglycemia
• Increased lipolysis, releasing free fatty acids
• Hepatic conversion of free fatty acids to ketone bodies, mainly beta-hydroxybutyrate and acetoacetate
• High-anion-gap metabolic acidosis due to ketone accumulation
• Osmotic diuresis due to hyperglycemia, causing dehydration and major electrolyte loss

Clinical features

Symptoms

• Polyuria, polydipsia, thirst
• Weakness and fatigue
• Nausea, vomiting, abdominal pain
• Weight loss
• Fever or symptoms of an underlying infection
• Altered mental state in severe cases

Signs

• Dehydration, dry mucosa, poor skin turgor
• Tachycardia and hypotension
• Tachypnea and deep, labored Kussmaul respiration
• Fruity or acetone odor on breath
• Abdominal tenderness
• Drowsiness, confusion, coma in severe DKA

Investigations

Essential tests

• Capillary and venous plasma glucose
• Venous blood gas: pH and bicarbonate
• Blood beta-hydroxybutyrate, preferred over urine ketones where available
• Serum electrolytes: sodium, potassium, chloride, bicarbonate
• Urea, creatinine, magnesium, phosphate
• Complete blood count
• Urinalysis and urine culture if infection suspected
• ECG, especially to detect potassium-related abnormalities or ischemia
• Blood cultures, chest radiograph, troponin, lipase, or other testing when clinically indicated

Typical biochemical abnormalities

• Hyperglycemia
• Positive blood or urine ketones
• Metabolic acidosis with low pH and low bicarbonate
• Raised anion gap
  Anion gap = Na⁺ − (Cl⁻ + HCO₃⁻)
• Raised urea and creatinine from dehydration
• Potassium may be initially high, normal, or low
• Corrected sodium may be low due to hyperglycemia

Management

1. Restore intravascular volume
2. Correct electrolyte deficits, particularly potassium
3. Stop ketogenesis with insulin
4. Identify and treat the precipitating cause
5. Monitor closely for complications

1. Initial assessment

• Assess airway, breathing, circulation, and mental status.
• Establish intravenous access.
• Record vital signs, fluid balance, urine output, body weight, and neurological status.
• Send initial blood tests and obtain ECG.
• Search actively for infection, myocardial infarction, stroke, pancreatitis, and insulin omission.

2. Fluid replacement

3. Potassium replacement

4. Insulin therapy

• Start regular insulin intravenously at 0.1 unit/kg/hour.
• A bolus is not routinely required when a suitable continuous infusion protocol is used.
• Aim for a glucose fall of about 50-75 mg/dL per hour.
• Continue insulin until ketoacidosis resolves, not merely until glucose normalizes.

• Add 5-10% dextrose to intravenous fluids.
• Reduce insulin infusion, commonly to 0.05 unit/kg/hour.
• Maintain glucose around 150-200 mg/dL while ketone clearance and acidosis correction continue.

5. Bicarbonate and phosphate

• Bicarbonate is not routinely indicated. It may be considered only in severe acidosis, usually when pH is <7.0.
• Phosphate is not routinely replaced. Consider replacement in severe hypophosphatemia, particularly if there is respiratory weakness, cardiac dysfunction, or significant muscle weakness.

6. Treat the precipitating cause

• Antibiotics for confirmed or strongly suspected infection
• Management of myocardial infarction, stroke, or pancreatitis
• Correction of insulin delivery problems, including insulin-pump malfunction
• Discontinuation of precipitating medications where appropriate
• Specialist review of possible SGLT2 inhibitor-associated euglycemic DKA

Monitoring

• Capillary glucose every 1-2 hours
• Electrolytes, bicarbonate, creatinine, venous pH, and beta-hydroxybutyrate about every 4 hours
• ECG where potassium abnormality is present
• Blood pressure, pulse, respiratory rate, oxygen saturation, mental status
• Fluid input, urine output, and cumulative fluid balance

Resolution of DKA

• Beta-hydroxybutyrate <0.6 mmol/L, and
• Venous pH ≥7.3 or bicarbonate ≥18 mmol/L

Complications of treatment

• Hypoglycemia
• Hypokalemia
• Fluid overload and pulmonary edema
• Hyperchloremic metabolic acidosis
• Cerebral edema, particularly in children and young adults
• Venous thrombosis in severely dehydrated patients

Prevention

• Do not stop basal insulin during illness without medical advice.
• Follow sick-day rules: monitor glucose and ketones more frequently, drink fluids, and seek help early.
• Know warning symptoms: vomiting, abdominal pain, deep breathing, increasing ketones, or persistent hyperglycemia.
• Review insulin technique, storage, adherence, affordability, and pump function.
• Arrange early diabetes follow-up after any DKA admission.

Conclusion

Organophosphorus (OP) Poisoning

Definition

Mechanism of Toxicity

• Muscarinic receptors: secretions, bronchospasm, bradycardia, miosis, diarrhea
• Nicotinic receptors: fasciculations, weakness, paralysis
• Central nervous system receptors: agitation, seizures, coma, respiratory depression

Clinical Features

Muscarinic features

• D: diarrhea and defecation
• U: urination
• M: miosis
• B: bronchorrhea and bronchospasm
• E: emesis
• L: lacrimation
• S: salivation and sweating

Nicotinic features

• Muscle fasciculations
• Muscle cramps
• Weakness
• Tachycardia or hypertension may occur initially
• Paralysis of respiratory muscles

Central nervous system features

• Anxiety, confusion, agitation
• Headache
• Seizures
• Drowsiness
• Coma
• Central respiratory depression

Diagnosis

History

• History of pesticide exposure, ingestion, spraying, farming work, or a characteristic chemical odor
• Possible intentional ingestion in self-harm

Examination

• Miosis
• Profuse oral and bronchial secretions
• Wheeze and crepitations
• Bradycardia
• Sweating
• Fasciculations and weakness
• Reduced consciousness

Investigations

• Pulse oximetry and arterial or venous blood gas
• ECG
• Blood glucose, complete blood count, electrolytes, renal and liver function
• Chest radiograph if aspiration or pulmonary edema is suspected
• Plasma pseudocholinesterase and red-cell acetylcholinesterase levels, if available

Management

1. Resuscitation: ABC approach

• Remove the patient from further exposure.
• Give high-flow oxygen.
• Suction excessive airway secretions.
• Establish intravenous access and monitor ECG, oxygen saturation, blood pressure, and consciousness.
• Intubate and ventilate early if there is hypoxia, severe bronchorrhea, respiratory muscle weakness, worsening consciousness, or seizures.
• Avoid succinylcholine during intubation because cholinesterase inhibition can prolong neuromuscular blockade.

2. Decontamination

• Remove contaminated clothing.
• Wash skin and hair thoroughly with soap and water.
• Irrigate eyes with water or saline if exposed.
• Gastric decontamination is not routine. Activated charcoal may be considered early after a significant ingestion only when the airway is protected and following local toxicology advice.
• Do not induce vomiting.

3. Atropine

Adult regimen

• Give 1-3 mg IV, then repeat and rapidly escalate, often doubling the dose every 3-5 minutes, until atropinization is achieved.
• Severe poisoning may require very large cumulative doses.
• Once stabilized, start an atropine infusion, commonly about 10-20% of the total loading dose per hour, and titrate to clinical response.

End points of atropinization

• Chest clear of bronchial secretions on auscultation
• Adequate air entry and oxygenation
• Drying of excessive secretions
• Improved blood pressure and heart rate

4. Pralidoxime

• 1-2 g IV over 15-30 minutes, followed by repeat dosing or continuous infusion according to local protocol.

5. Diazepam or other benzodiazepines

• Seizures
• Severe agitation
• Marked muscle fasciculations
• Sedation during mechanical ventilation

6. Supportive care

• Intravenous fluids for hypotension, while avoiding fluid overload.
• Vasopressors if shock persists after atropinization and adequate fluid resuscitation.
• Treat aspiration pneumonia or other confirmed complications.
• Correct hypoxia, acidosis, electrolyte disturbances, and hypoglycemia.
• Monitor closely in a high-dependency unit or ICU.

Important Complications

Intermediate syndrome

• Proximal muscle weakness
• Neck flexor weakness
• Cranial nerve palsies
• Respiratory muscle paralysis

Organophosphate-induced delayed neuropathy

• Distal weakness
• Paraesthesia
• Foot drop
• Gait difficulty

Other complications

• Aspiration pneumonia
• Pulmonary edema
• Cardiac arrhythmias
• Pancreatitis
• Seizures
• Coma
• Recurrent cholinergic features after early cessation of atropine

Prognosis

Prevention

• Store pesticides securely and away from food.
• Use gloves, masks, protective clothing, and safe spraying techniques.
• Ensure prompt washing after occupational exposure.
• Restrict access to highly hazardous pesticides.
• After intentional ingestion, arrange psychiatric assessment and follow-up once medically stable.

Conclusion