Liver: Comprehensive Review

1. LIVER ANATOMY

Weight and Location

Embryology

Lobes and Segments

• Anatomical lobes: Right and left, divided by the falciform ligament anteriorly
• Smaller lobes: Caudate lobe (posterior-superior, drains directly into IVC - important in Budd-Chiari syndrome) and quadrate lobe (undersurface of medial left lobe)
• Riedel's lobe: An anatomic extension of the right lobe that may feel like a mobile tumour
• Couinaud segments: The liver is divided into 8 functional segments, each supplied by terminal branches of the portal vein and hepatic artery, and drained by its own bile duct and hepatic vein

Ligaments and Peritoneal Reflections

Blood Supply

• Portal vein: ~80% of blood flow (70-80%), nutrient-rich blood from GI tract, spleen, pancreas, and gallbladder
• Hepatic artery (branch of coeliac trunk): ~20% of blood flow, oxygen-rich; each supplies approximately half the oxygen to the liver, making it highly resistant to infarction
• Portal vein is formed by the union of the splenic vein and superior mesenteric vein
• Venous drainage: Right and left hepatic veins exit posteriorly into the IVC near its entry into the right atrium

Biliary Drainage

Nerve Supply

Key Functions of the Liver (Summary)

• Temperature regulation and pH balance
• Synthesis of clotting factors (I, II, V, VII, IX, X, XI)
• Glucose metabolism: glycolysis and gluconeogenesis
• Urea formation from protein catabolism
• Bilirubin formation from haem degradation
• Drug and hormone metabolism (Cytochrome P450)
• Vitamin storage: A, D, E, K, B12
• Albumin production for transport of fatty acids, steroids, waste
• Immunological function via Kupffer cells (mononuclear phagocyte system)
• Removal of gut endotoxins and foreign antigens
• Bailey & Love's Surgery, 28th Ed

2. LIVER FUNCTION TESTS (LFTs)

Categories of LFTs

Individual Tests

• Activities significantly elevated days before onset of jaundice in acute viral hepatitis
• ALT is more specific for liver disease - not elevated in cardiac/skeletal muscle injury
• AST is elevated in diseases of liver, heart, lungs, kidneys, and muscle
• High ALT > AST: viral hepatitis
• AST:ALT ratio >2:1: suggests alcoholic liver disease

• Elevated in obstructive jaundice and cholestatic conditions
• Also elevated in bone disease (remember: bone, liver, placenta isoforms)

• Elevated with bile duct injury; sensitive marker for alcohol use and cholestasis

• Increase suggests cholestasis; obstruction of biliary tree must be excluded
• Fractionated analysis: direct (conjugated) vs indirect (unconjugated)

• Reflects hepatic synthetic function; low in chronic liver disease
• Half-life ~20 days (not useful for acute liver failure)

• Reflects synthesis of clotting factors (II, VII, IX, X) by the liver
• Most sensitive short-term synthetic marker (factor VII has half-life ~6 hours)
• Prolonged PT = impaired synthetic function

Pattern Interpretation

• Tietz Textbook of Laboratory Medicine, 7th Ed; Sleisenger & Fordtran's GI and Liver Disease

3. PORTAL HYPERTENSION

Definition and Normal Values

• Portal vein pressure normally = 5-7 mmHg; portal flow = 1000-1200 mL/min
• Portal hypertension = clinically significant when portal pressure gradient >10 mmHg; variceal bleeding risk increases at >12 mmHg

Classification by Site of Obstruction

Pathophysiology

1. Structural (static) resistance: Progressive collagen deposition and nodule formation distort sinusoidal blood flow → increased intrahepatic resistance
2. Dynamic resistance: Contraction of hepatic stellate cells (HSCs), imbalance of intrahepatic vasodilators (notably nitric oxide - deficient intrahepatic) and vasoconstrictors, injured hepatocytes

• In the splanchnic circulation paradoxically, NO is overproduced, causing splanchnic vasodilation, which increases portal blood flow and worsens portal hypertension

Portosystemic Collaterals (Sites of Varices)

Complications of Portal Hypertension

• Results from splanchnic arterial vasodilation → effective arterial hypovolemia → activation of renin-angiotensin-aldosterone system (RAAS) + sympathetic nervous system → renal sodium and water retention
• Inflammatory mediators (PAMPs from bacterial translocation, DAMPs from injured liver) further impair circulatory function

• Most dangerous complication; oesophageal varices most common bleeding source

• Impaired ammonia metabolism + abnormal neurotransmitters (portosystemic shunting bypasses liver)

• Renal vasoconstriction secondary to splanchnic vasodilation and reduced effective circulating volume

• Thrombocytopenia, anaemia, leucopenia

• Sleisenger & Fordtran's GI and Liver Disease; Tietz Textbook of Laboratory Medicine

4. LIVER ABSCESS

Epidemiology

• Incidence: approximately 1 in 5000 hospital admissions (fairly constant rate)
• Increased risk in: elderly, diabetics, immunosuppressed
• Worldwide, bacteria remain the most common cause

Types and Causative Organisms

A. Pyogenic (Bacterial) Liver Abscess

• Usually polymicrobial; most common organisms: Klebsiella, E. coli, and the Streptococcus milleri group
• Routes of infection:
  1. Biliary tract pathology - most common source (35%) - cholangitis, bile duct obstruction
  2. Portal spread from GI tract (20%) - diverticulitis, appendicitis
  3. Contiguous spread from subphrenic/intra-abdominal collections
  4. Bacteraemia secondary to trauma
  5. Infected cysts, necrotic tumours post-chemotherapy
  6. Cryptogenic (no source identified) - 10%

B. Amoebic Liver Abscess

• Caused by Entamoeba histolytica
• Endemic in tropical/subtropical regions
• "Anchovy sauce" appearance of aspirate
• Responds well to metronidazole (medical treatment often sufficient)

Clinical Features

• Fever (most consistent finding)
• Anorexia, malaise
• Right upper quadrant discomfort/pain
• Hepatomegaly
• Occasionally jaundice

Diagnosis

• Suggested by finding of a multiloculated cystic mass on ultrasonography or CT scan
• Confirmed by aspiration (for microbiology and culture)
• CT scan shows air-fluid level and rim enhancement

Differential Diagnosis

Treatment

• Metronidazole and clindamycin: wide anaerobic coverage, excellent penetration into abscess cavity
• Third-generation cephalosporins and aminoglycosides: effective against Gram-negative organisms

• Occur when initial lesion was large, multiple abscesses present, or continued biliary communication
• May require surgical intervention or prolonged drainage

Prognosis

• Overall mortality has declined with improved imaging and antimicrobial therapy
• Recurrence rate: 12-38%, especially if the organism is not identified or the patient has diabetes
• Outcome increasingly dependent on underlying cause and comorbidities
• Bailey & Love's Surgery, 28th Ed; Current Surgical Therapy, 14th Ed

5. HYDATID CYST (Echinococcosis)

Aetiology / Life Cycle

• A zoonosis caused by the larval stage of Echinococcus tapeworms
• Three species: E. granulosus (most common), E. multilocularis, E. ligartus
• Definitive host: Dog (adult tapeworm attached to ileal villi; thousands of ova shed in faeces)
• Intermediate host: Sheep (usual); humans are accidental intermediate hosts - end-stage for the parasite
• No human-to-human transmission
• Endemic: Mediterranean, Middle East, Far East, South America, Australia, New Zealand, East Africa

Cyst Structure

• Pericyst: Outer fibrous capsule from host tissues
• Ectocyst: Outer gelatinous membrane (from parasite)
• Endocyst: Inner germinal membrane (from parasite)
• Brood capsules: Intracystic masses producing scoleces (future worm heads)
• Hydatid sand: Free brood capsules and scoleces floating in hydatid fluid
• Daughter cysts: True replicas of the mother cyst

Epidemiology and Clinical Features

• Equal sex distribution; average age ~45 years
• ~75% in right lobe of liver; usually solitary
• Largely asymptomatic until complications occur
• Symptoms: abdominal pain, dyspepsia, vomiting
• Most frequent sign: hepatomegaly
• Jaundice and fever: each ~8% of patients
• Complications:
  • Bacterial superinfection (mimics pyogenic abscess)
  • Rupture into biliary tree (biliary colic, jaundice, cholangitis)
  • Rupture into bronchial tree (cough, haemoptysis)
  • Free rupture into peritoneum/pleura/pericardium → disseminated echinococcosis or fatal anaphylactic reaction (emergency presentation)

Diagnosis

• Ultrasound: Most widely used worldwide (available, affordable, accurate)
• CT scan: Best technique - space-occupying lesion with smooth outline and septa

• Serology: Available but plagued by low sensitivity and specificity; used when imaging is inconclusive
• Note: Calcification is highly suggestive but does not always imply an inactive/dead cyst

Treatment

• Active cysts should first receive a full course of albendazole before any procedure
• Also used when surgery is not possible

• Aspiration → injection of scolicidal agent (povidone-iodine or hypertonic saline) → re-aspiration

1. Laparoscopic marsupialisation (deroofing): Cyst aspirated → scolicidal agent injected → endocyst + daughter cysts removed → biliary communication oversewn → omentoplasty
2. Pericystectomy: Complete removal with fibrous pericyst
3. Hepatic segmentectomy: For deeply located or complex cysts

• Asymptomatic and inactive cysts (CE4, CE5) - leave alone, monitor by ultrasound
• Never aspirate without pre-treatment (risk of anaphylaxis and seeding)
• Multidisciplinary approach: hepatobiliary surgeon + physician + interventional radiologist
• Increasingly: laparoscopic approach

• Sabiston Textbook of Surgery, 22nd Ed; Bailey & Love's Surgery, 28th Ed

Quick Comparison: Liver Abscess vs Hydatid Cyst

Liver - Bailey & Love's Short Practice of Surgery (28th Ed)

1. LIVER ANATOMY

Embryology

Summary Box - Liver Anatomy Key Points

• There are two anatomical lobes with a separate blood supply, bile duct and venous drainage
• There is a dual blood supply: 80% portal vein and 20% hepatic artery
• The liver regenerates to 90-100% of its previous volume following resection
• Resection is based on anatomical lines to preserve maximal functioning liver and blood supply

Ligaments and Peritoneal Reflections

Blood Supply

2. LIVER BLOOD TESTS (LFTs)

"The liver performs a myriad of biochemical, metabolic and immunological functions. Anhepatic humans survive for 24-48 hours. It is the only organ in the body that regenerates. Awareness of currently available liver blood tests and their significance is essential."

Main Functions of the Liver (Summary Box 69.2)

• Maintaining core body temperature
• pH balance and correction of lactic acidosis
• Synthesis of clotting factors
• Glucose metabolism, glycolysis and gluconeogenesis
• Urea formation from protein catabolism
• Bilirubin formation from haemoglobin after breakdown of effete red cells in the spleen
• Drug and hormone metabolism and excretion
• Removal of gut endotoxins and foreign antigens
• Vitamin and mineral storage: A, D, E, K and B12
• Immunological function as part of the mononuclear phagocyte system
• Albumin production for transport of fatty acids, steroids and waste products
• Angiotensin synthesis
• Cytochrome P450 detoxifies contaminants, pollutants, insecticides, food additives and alcohol

Clinical Signs of Liver Dysfunction

Assessment of Chronic Liver Disease

Features of Chronic Liver Disease (Summary Box 69.6)

• Grade 1: Inverted sleep pattern, agitation, forgetfulness, irritability, apraxia
• Grade 2: Lethargy, time and/or place disorientation, personality change, ataxia
• Grade 3: Somnolence to semistupor but responds to verbal stimuli, place disorientation, asterixis, hyperactive reflexes
• Grade 4: Coma

King's College Criteria (non-paracetamol ALF - poor prognosis indicators)

• Duration of jaundice before development of encephalopathy >7 days
• PT >50 seconds (approximate INR >3.5)
• Serum bilirubin >18 mg/dL (300 µmol/L)

Causes of Acute Liver Failure (Summary Box 69.3)

• Viral hepatitis (A, B, C, D, E)
• Drug reactions: halothane, isoniazid-rifampicin, antidepressants, NSAIDs, valproic acid
• Paracetamol overdose
• Prescription medicines: antibiotics, anticonvulsants, statins
• Mushroom poisoning
• Toxins (carbon tetrachloride)
• Shock and multiorgan failure
• Autoimmune disease
• Acute Budd-Chiari syndrome
• Metabolic: Wilson's disease
• Cancer
• Fatty liver of pregnancy
• Heat stroke; Reye's syndrome (children post-viral infection)
• SARS-CoV-2 can cause liver failure in up to 20% of patients with a severe episode

3. PORTAL HYPERTENSION

"Portal hypertension is most commonly due to liver cirrhosis, although it also occurs with extrahepatic portal vein occlusion, intrahepatic veno-occlusive disease and occlusion of the main hepatic veins (Budd-Chiari syndrome)."

1. Ascites
2. Oesophageal varices
3. Portosystemic shunting for problems not managed by other methods
4. Left-sided portal hypertension and hypersplenism

Causes of Portal Hypertension (Summary Box 69.9)

Management of Variceal Bleeding

• Admit to ITU; large-bore peripheral cannulae; resuscitation with blood
• LFTs reveal underlying liver disease; coagulation profile identifies coagulopathy
• Hypervolaemia may increase portal pressure and exacerbate bleeding
• Vitamin K 10 mg IV; coagulopathy requires FFP + major transfusion protocol
• Thrombocytopenia secondary to hypersplenism treated if platelet count <50 × 10⁹/L
• Treatment protocols: splanchnic vasoconstrictors (terlipressin, octreotide, somatostatin) + prophylactic antibiotics
• 30% will have a non-variceal source of bleeding - confirm endoscopically once haemodynamically stable

1. Blood transfusion
2. Correct coagulopathy
3. Oesophageal balloon tamponade (Sengstaken-Blakemore or Minnesota tube)
4. Terlipressin (drug therapy)
5. Endoscopic sclerotherapy or banding
6. Assess portal vein patency (Doppler USS or CT)
7. TIPSS (Transjugular Intrahepatic Portosystemic Stent Shunt)
8. Surgery: portosystemic shunts / splenectomy and gastric devascularisation / Sugiura procedure

• Side-to-side portocaval anastomosis
• End-to-side portocaval
• Mesocaval 'H graft'
• Splenorenal anastomosis
• Selective shunts have lower incidence of encephalopathy; no evidence prophylactic shunting is beneficial

Ascites Management (Summary Box 69.11 & 69.12)

• Imaging (USS/CT): irregular cirrhotic liver, portal vein patency, splenomegaly
• Aspiration: culture/microscopy, protein content, cytology, amylase level
• SAAG (Serum-Ascites Albumin Gradient): High gradient (>1.1 g/dL) indicates portal hypertension

1. Salt restriction
2. Diuretics: spironolactone or frusemide (regular biochemical monitoring required)
3. Abdominal paracentesis
4. Peritoneovenous shunts
5. TIPSS
6. Liver transplantation

4. LIVER ABSCESS

Epidemiology

• Occurs at a fairly constant rate of approximately 1 in 5000 hospital admissions
• Bacterial, parasitic and fungal organisms can cause liver abscess; worldwide, bacteria remain the most common
• Infection is usually polymicrobial: Klebsiella, Escherichia coli and the Streptococcus milleri group are the usual organisms
• Increased incidence in: elderly, diabetics, and the immunosuppressed

Sources of Infection

1. Biliary tract pathology - most common source (35%)
2. Portal spread from GI tract (diverticulitis, appendicitis) - (20%)
3. Contiguous spread from subphrenic or intra-abdominal collections
4. Bacteraemia secondary to trauma
5. Infected cysts and necrotic tumours following chemotherapy
6. Cryptogenic (cause not identified) - 10%

Clinical Features

• Anorexia, fever, malaise
• Right upper quadrant discomfort

Diagnosis

• Suggested by finding of a multiloculated cystic mass on ultrasonography or CT scan
• Confirmed by aspiration
• CT shows air-fluid level and rim enhancement

Treatment

• Metronidazole + clindamycin: wide anaerobic coverage, excellent penetration into the abscess cavity
• Third-generation cephalosporins + aminoglycosides: very effective against most Gram-negative organisms

Recurrent or Refractory Abscesses

• Occur when initial lesion was large, abscesses were multiple, or there is continued communication with the biliary tree
• Recurrence rate: 12-38% (depending on whether organism identified and whether patient has diabetes)
• Re-aspiration or insertion of a drain required
• If unsuccessful, laparoscopy (allows full examination of peritoneal cavity, especially when source not identified) has replaced laparotomy

Prognosis

• Overall mortality has declined because of improved imaging and effective antimicrobial therapy
• Outcome increasingly dependent on underlying cause and comorbidities

5. HYDATID CYST

Summary Box 69.13 - Infections of the Liver (Bailey & Love Key Points)

• Pyogenic liver abscesses: 1/5000 admissions
• Worldwide billions of people have parasitic infections
• Parasitic infections cause liver abscess and biliary tract damage
• Biliary tract involvement predisposes to cholangiocarcinoma
• Parasitic infections mimic pyogenic abscesses
• Obstructive jaundice from calcified flukes or biliary tract involvement

Aetiology and Life Cycle

• Definitive host: Dog (adult worm in small intestine; eggs passed in faeces - highly resistant to temperature extremes, survive long periods)
• Intermediate hosts: Sheep, cattle, and humans (accidental)
• Transmission to humans: Close contact with infected dog → oral contamination by ova → entry into GI tract → development of larval stage in organs
• The liver is the organ most often affected; the lung is next most common
• E. multilocularis: variant in colder climates - spreads by actual invasion rather than expansion

Cyst Structure - Three Layers

1. Outer pericyst: Derived from compressed host organ tissues
2. Intermediate hyaline ectocyst: Non-infective
3. Inner endocyst: The germinal membrane - contains viable parasites that can separate, forming daughter cysts

WHO Classification (WHO-IWGE, 2003) - Ultrasound Staging

• Group 1 (Active): Cysts larger than 2 cm, often fertile
• Group 2 (Transitional): Cysts starting to degenerate; host resistance or treatment; may still contain viable protoscolices
• Group 3 (Inactive): Degenerated, partially or totally calcified; unlikely to contain viable protoscolices

Clinical Features (Summary Box 6.9)

• In the UK, the usual sufferer is a sheep farmer
• While any organ may be involved, the liver is by far the most commonly affected
• Elective clinical presentation: gradually enlarging painful mass in the right upper quadrant (hepatic lesion causes dull pain from stretching of the liver capsule)
• Disease may be asymptomatic - discovered coincidentally at postmortem or on incidental imaging
• Emergency presentation: anaphylactic shock due to rupture of the hydatid cyst
• CT scan is the best imaging technique - diagnostic feature is a space-occupying lesion with a smooth outline with septa

Treatment (Summary Box - Hydatid Cyst of the Liver)

• Ideally managed in a tertiary unit by a multidisciplinary team of hepatobiliary surgeon, physician and interventional radiologist
• Leave asymptomatic and inactive cysts (CE4, CE5) alone - monitor size by ultrasonography
• Active cysts: First treat with a full course of albendazole
• Several procedures available: PAIR, pericystectomy with omentoplasty, hepatic segmentectomy
• Increasingly, a laparoscopic approach is being tried

• Options range from liver resection or local excision to deroofing with evacuation of contents
• Contamination of peritoneal cavity with active hydatid daughters must be avoided by:
  • Continuing albendazole + adding preoperative praziquantel
  • Packing peritoneal cavity with 20% hypertonic saline-soaked packs
  • Instilling 20% hypertonic saline into cyst before opening
• Biliary communication must be actively sought and sutured
• Omentoplasty (pedicled greater omentum) reduces bile leaks and infection
• Calcified cysts may be dead; if doubt exists whether cyst is active, follow on ultrasonography

• Percutaneous Aspiration, Injection (scolicidal agent - povidone-iodine or hypertonic saline), Re-aspiration

• Cyst aspirated (avoiding spillage) → scolicidal agent instilled → endocyst + daughter cysts removed → biliary communication oversewn → pedicled omentum sutured to margins (omentoplasty)
• If cyst small and superficial: cystopericystectomy (entire cyst removed intact)

Pulmonary Hydatid Disease

• Lung is the second commonest organ affected
• Right lung, lower lobes slightly more often involved; usually single
• "Meniscus" / "Crescent" sign on CXR: air between pericyst and laminated membrane = sign of impending rupture
• "Water-lily sign" on CT: collapsed endocyst floating on residual fluid after rupture
• Treatment: primarily surgical

All content above is drawn exclusively from Bailey and Love's Short Practice of Surgery, 28th Edition (ISBN 9780367548117).

Hypertension in Pediatrics

1. DEFINITION AND CLASSIFICATION

BP Classification Table (AAP 2017)

• Elevated BP = sustained on 3 or more occasions
• Normative data is based on children with normal BMI (NHANES data)
• For children ≥13 years: definitions align with adult AHA/ACC criteria
• Tintinalli's Emergency Medicine; National Kidney Foundation Primer

Hypertensive Crisis Terminology

• Hypertensive urgency: Severely elevated BP without evidence of target organ damage
• Hypertensive emergency: BP exceeding the 99th percentile for age/sex with acute end-organ damage requiring immediate treatment
• Acute severe hypertension (2017 AAP preferred term): Any acute symptomatic presentation of hypertension
• Target organs most commonly damaged: CNS, kidneys, cardiovascular system
• Hypertensive crises in younger children are usually secondary to an underlying disease

2. EPIDEMIOLOGY

• Prevalence of clinical hypertension in pediatrics: approximately 3.5%
• Essential hypertension now affects 3-5% of US adolescents
• Boys, adolescents, and Hispanic and African American races have higher rates in the USA
• Associated risk factors: obesity, family history, sedentary lifestyle, high dietary sodium, African ancestry, history of prematurity and/or low birth weight
• If left untreated: increased risk of adult hypertension, cardiovascular disease, and metabolic syndrome
• Rosen's Emergency Medicine; Comprehensive Clinical Nephrology

3. AETIOLOGY

Primary (Essential) Hypertension

• Once considered rare in children; now routinely encountered in clinical practice
• More prevalent in adolescents, especially obese adolescents
• No identifiable underlying cause
• Risk factors: obesity, family history, sedentary lifestyle, high sodium diet

Secondary Hypertension

Causes by Age Group

Summary of Secondary Causes (By Category)

• Renal (most common overall): Glomerulonephritis, haemolytic-uraemic syndrome, FSGS, renal dysplasia, polycystic kidney disease, chronic infections, obstructive lesions; renovascular disease (renal artery stenosis, fibromuscular dysplasia) - most common secondary cause in children
• Cardiovascular: Coarctation of the aorta
• Endocrine: Pheochromocytoma/neuroblastoma (catecholamines), Cushing's syndrome (cortisol excess), hyperthyroidism
• Neurological: Elevated intracranial pressure (space-occupying lesions, acute haemorrhage, infection, CSF obstruction) → body elevates BP to maintain cerebral perfusion pressure
• Medications/Toxins: Oral contraceptives, steroids, stimulants (cocaine, amphetamines), NSAIDs, calcineurin inhibitors
• Genetic/Structural: Neurofibromatosis type 1, monogenic tubular disorders
• Neonatal special risk: Umbilical vein catheter manipulation → risk of renal vein thrombosis

4. CLINICAL FEATURES

Symptoms (Range from Mild to Life-Threatening)

History Points to Elicit

• Maternal complications at birth, gestational age
• Umbilical vein catheter manipulation (risk of renal vein thrombosis)
• Dietary salt intake
• Family history of hypertension
• Palpitations, weight loss, flushing, diarrhoea (endocrine causes)
• Snoring/pauses in sleep (obstructive sleep apnoea)
• Medications and substances
• Rosen's Emergency Medicine

Physical Examination

• 4-extremity blood pressure - to look for coarctation of the aorta (BP higher in arms than legs)
• Signs of secondary causes: café-au-lait spots (NF1), moon face/buffalo hump (Cushing's), abdominal bruit (renal artery stenosis)

5. BP MEASUREMENT

• Gold standard: Auscultation - all normative pediatric data generated by auscultation
• Oscillometric devices: Known to overestimate BP by up to 5-10 mmHg in children; elevated readings must always be confirmed by manual auscultation
• Confirmed hypertension = BP elevated on 3 or more separate occasions

Ambulatory Blood Pressure Monitoring (ABPM)

• White-coat hypertension: Elevated office BP + normal ABPM (isolated office hypertension)
• Masked hypertension: Normal office BP + hypertension on ABPM
• Advantages: Distinguishes white-coat from true HTN, detects masked HTN, characterises BP during daily activities and sleep, more closely correlates with end-organ changes (LVH) than office-based readings
• 2017 AAP guidelines: Recommend ABPM confirmation of elevated readings where possible; children with CKD + HTN should have annual ABPM
• National Kidney Foundation Primer

6. INVESTIGATIONS / DIAGNOSTIC EVALUATION

Initial Workup (for all children with confirmed HTN)

• Basic metabolic panel (BMP): Electrolytes, creatinine, BUN
• Urinalysis (UA): Haematuria, proteinuria (suggests renal parenchymal disease)
• Lipid panel: Fasting lipid profile
• Kidney ultrasound: Renal parenchymal disease, structural abnormalities

Additional Tests Based on Clinical Context

• Rosen's Emergency Medicine; National Kidney Foundation Primer

7. MANAGEMENT

Long-Term Treatment Goals

• Achieve BP <90th percentile, or <130/80 mmHg in adolescents ≥13 years
• Children with CKD: target <50th percentile based on ABPM
• Purpose: Reduce end-organ damage and cardiovascular risk in adulthood

A. Lifestyle Modifications (First-Line for Essential Hypertension)

• DASH diet: Dietary Approaches to Stop Hypertension - low sodium, plant-based, whole grains, low-fat dairy, lean meats
• Moderate to vigorous exercise on most days of the week
• Achievement and maintenance of normal BMI
• Limited screen time
• Avoidance of precipitating medications/substances

B. Pharmacologic Therapy - Indications

1. HTN persists despite lifestyle changes
2. Secondary hypertension identified
3. HTN associated with end-organ damage
4. HTN associated with chronic disorders (diabetes, CKD)
5. Stage 2 hypertension in adolescents

Antihypertensive Drug Classes (Approved for Paediatric Use)

C. Management of Hypertensive Emergency

• Immediate IV antihypertensives - avoid rapid correction (risk of cerebral ischaemia)
• Target: Reduce BP by no more than 25% in the first 8 hours
• IV agents used: Labetalol, hydralazine, nicardipine, sodium nitroprusside
• Identify and treat underlying cause
• Monitor for end-organ damage: neurological status, urine output, ECG

8. COMPLICATIONS / END-ORGAN DAMAGE

9. QUICK SUMMARY - KEY POINTS

Syndromes That Include Hypertension

1. ENDOCRINE SYNDROMES

A. Conn Syndrome (Primary Aldosteronism)

• Pathology: Tumour of zona glomerulosa cells (or bilateral adrenal hyperplasia) → excess aldosterone secretion
• Mechanism: Aldosterone drives renal sodium and water retention → increased blood volume and BP
• Key features:
  • Hypertension (almost always present)
  • Hypokalemia (muscle weakness, occasionally paralysis from depressed action potentials)
  • Mild metabolic alkalosis
  • Slight increase in extracellular fluid and blood volume
  • Mild hypernatraemia (usually <4-6 mEq/L rise)
  • Suppressed plasma renin (hallmark diagnostic criterion - due to feedback suppression from volume expansion)
• Treatment: Surgical removal of tumour OR spironolactone/eplerenone (mineralocorticoid receptor antagonists)
• Guyton and Hall Medical Physiology; Fuster & Hurst's The Heart

B. Cushing Syndrome (Glucocorticoid Excess / Hypercortisolism)

• Pathology: Excess cortisol from any cause (exogenous steroids, ACTH-dependent, ACTH-independent)
• Key clinical features (with approximate frequencies):
  • Truncal obesity (90%)
  • Hypertension (85%) - due to mineralocorticoid effects of cortisol + increased angiotensinogen
  • Decreased glucose tolerance / diabetes (80%)
  • Hirsutism (70%)
  • Wide purple abdominal striae (65%)
  • Osteoporosis (55%)
  • Moon face, plethoric facies
  • Easy bruising, thin skin
  • Buffalo hump (dorsocervical fat pad)
  • Proximal muscle weakness
• Mechanism of hypertension: Cortisol has weak mineralocorticoid activity; also upregulates angiotensinogen, increases vascular sensitivity to catecholamines
• Harvey Cushing originally described 11 patients with moon facies, truncal obesity, hypertension, and other features in 1932
• Swanson's Family Medicine Review; Campbell-Walsh-Wein Urology

C. Pheochromocytoma

• Pathology: Catecholamine-secreting tumour of adrenal medulla (or extra-adrenal paraganglioma)
• Classic presentation: "Spells" of headache, hyperhidrosis, palpitations, cardiac arrhythmias, tremulousness, anxiety
• Hypertension features:
  • Paroxysmal hypertension is the classic sign (but documented in only ~30-50% of patients)
  • Can occur on background of baseline essential hypertension
  • ~5% of patients remain normotensive
  • Norepinephrine-secreting → alpha-adrenergic vasoconstriction → predominantly diastolic hypertension
  • Epinephrine-secreting → beta-adrenergic cardiac stimulation → mainly systolic hypertension + tachycardia + sweating, tremors, flushing
  • Patients with epinephrine-predominant tumours: hypertension alternating with hypotension
  • Can lead to intracranial haemorrhage; seizures in ~5%
• Mechanism: Periodic bursts of catecholamine release → moderate to severe hypertensive episodes → target organ injury
• Note: BP is often only modestly correlated with plasma catecholamine levels
• Fuster & Hurst's The Heart; Campbell-Walsh-Wein Urology

D. Congenital Adrenal Hyperplasia (CAH) - certain forms

• Most common form (21-β-hydroxylase deficiency): Usually causes hypotension from salt-wasting
• 11-β-hydroxylase deficiency form: Accumulation of deoxycorticosterone (mineralocorticoid activity) → hypertension + virilisation
• 17-α-hydroxylase deficiency: Excess mineralocorticoids → hypertension + hypokalemia + absent puberty
• Guyton and Hall Medical Physiology

2. RENAL / GENETIC SYNDROMES

E. Liddle Syndrome

• Genetics: Autosomal dominant gain-of-function mutation in ENaC (epithelial sodium channel - beta or gamma subunit C-terminus), the amiloride-sensitive Na⁺ channel of the collecting tubule
• Mechanism: ENaC constitutively overexpressed at cell membrane, not inhibited by intracellular Na⁺ → permanent sodium retention → hypertension
• Key features:
  • Severe hypertension
  • Hypokalemia
  • Suppressed aldosterone and suppressed renin (distinguishes from Conn's)
  • Resembles hyperaldosteronism but aldosterone is actually low ("apparent mineralocorticoid excess" phenotype)
• Pharmacology: Resistant to spironolactone (mineralocorticoid receptor blocker); responsive to amiloride and triamterene (ENaC blockers) - this is the diagnostic differentiator
• Distinguished from AME syndrome: AME responds to both spironolactone and amiloride; Liddle responds only to amiloride
• Brenner & Rector's The Kidney

F. Gordon Syndrome (Pseudohypoaldosteronism Type 2 / Familial Hyperkalemic Hypertension)

• Mirror image of Gitelman syndrome
• Genetics: Autosomal dominant; mutations in WNK kinases (WNK1, WNK4) or KLHL3/CUL3
• Key features:
  • Hypertension
  • Hyperkalemia (in contrast to Conn's/Liddle's which have hypokalemia)
  • Mild hyperchloremic metabolic acidosis (non-anion gap)
  • Normal GFR
  • Hypercalciuria; normal serum magnesium
• Mechanism: Increased NaCl reabsorption in distal tubule → volume expansion → hypertension + impaired K⁺/H⁺ secretion → hyperkalemia + acidosis
• Comprehensive Clinical Nephrology; National Kidney Foundation Primer

G. Apparent Mineralocorticoid Excess (AME) Syndrome

• Deficiency of 11-β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)
• Normally, 11β-HSD2 converts cortisol (which binds mineralocorticoid receptor) to inactive cortisone in the kidney
• When deficient: cortisol acts like aldosterone → sodium retention, potassium wasting → hypertension
• Features: severe early-onset hypertension, hypokalemia, suppressed aldosterone and renin
• Differential: responds to both spironolactone and amiloride (unlike Liddle's)

3. CARDIOVASCULAR SYNDROMES

H. Coarctation of the Aorta

• Structural narrowing of the descending aorta (usually at or just distal to ductus arteriosus)
• Hypertension pattern: Upper body/arm hypertension with reduced or absent femoral pulses
• Classical finding: BP in legs lower than arms (normally legs > arms by ~20 mmHg)
• A key secondary cause of hypertension in neonates and children
• Associated with Turner syndrome, bicuspid aortic valve
• May go undiagnosed depending on degree of narrowing

4. OBSTETRIC SYNDROMES

I. Pre-eclampsia

• Definition: New-onset hypertension (SBP ≥140 mmHg AND/OR DBP ≥90 mmHg) after 20th week of gestation + at least one additional feature (proteinuria, thrombocytopenia, renal insufficiency, impaired liver function, pulmonary oedema, cerebral/visual symptoms)
• Mechanism: Abnormal cytotrophoblast invasion of spiral arterioles → reduced uteroplacental perfusion → placental ischaemia → widespread maternal vascular endothelial dysfunction:
  • Enhanced ET-1, thromboxane, superoxide
  • Increased vascular sensitivity to Angiotensin II
  • Decreased NO and prostacyclin (vasodilators)
  • Elevated sFlt-1 (soluble VEGF receptor) → sequesters free VEGF and PlGF → impaired angiogenesis + renal endotheliosis + proteinuria
• Progression to eclampsia: seizures + high risk of fetal and maternal mortality
• Hypertension remits after delivery - placenta is the central culprit
• Complicates up to 10% of pregnancies

HELLP Syndrome

• Haemolysis, Elevated Liver enzymes, Low Platelets
• Severe variant of pre-eclampsia
• Features: hypertension + haemolysis + elevated AST/ALT + thrombocytopenia
• Fuster & Hurst's The Heart; Brenner & Rector's The Kidney

5. METABOLIC SYNDROME

J. Metabolic Syndrome (Syndrome X / Insulin Resistance Syndrome)

• Characterised by the cluster of:
  • Hypertension
  • Insulin resistance / impaired glucose tolerance / type 2 diabetes
  • Dyslipidaemia (high triglycerides, low HDL)
  • Central/truncal obesity (increased waist circumference)
• Associated with increased risk for diabetes and cardiovascular disease
• Obstructive sleep apnoea may predict metabolic syndrome even in the absence of other features
• Antipsychotic medications (especially clozapine, olanzapine) are a cause - up to 40% of patients on long-term antipsychotics have impaired glucose tolerance
• Treatment: weight reduction, increased physical activity, metformin; GLP-1 agonists (liraglutide) show benefit
• Goldman-Cecil Medicine

6. NEUROLOGICAL / OTHER SYNDROMES

K. Obstructive Sleep Apnoea (OSA) Syndrome

• Commonly associated with: hypertension, obesity, increased proinflammatory cytokines, impaired glucose tolerance, insulin resistance
• Mechanism: intermittent hypoxia → sympathetic activation → sustained hypertension
• May predict metabolic syndrome independently
• Harrison's Principles of Internal Medicine

L. Neurofibromatosis Type 1 (NF1)

• Hypertension in NF1 may result from renal artery stenosis (fibromuscular dysplasia involving renal vasculature) or pheochromocytoma (2-5% of NF1 patients)

M. Turner Syndrome

• Hypertension secondary to coarctation of the aorta (present in ~10-20%) and intrinsic cardiovascular abnormalities

Quick Reference Summary Table