Orris

provide a brief of the following diseases- Drug Reaction with Eosinophilia and systemic symptoms (DRESS) syndrome ; Non-cirrhotic portal fibrosis with portal hypertension, oesophageal varicose and pulmonary aspergillosis ; Guillain Barre syndrome & Myasthenia Gravis ; Posterior Reversible Encephalopathy Syndrome ; Acute non- hemorrhagic infarct in left parietal lobe ; Peripheral neuropathy in K/C/O rheumatoid arthritis ; Hodgkin lymphoma ; Inflammatory bowel disease- Crohn’s disease; Lipoma; Epididymoorchitis

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I now have sufficient textbook data combined with my medical knowledge to deliver comprehensive briefs for all 10 conditions. Here is the complete compilation:

Disease Briefs

1. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome

Definition: DRESS (also called Drug-Induced Hypersensitivity Syndrome / DiHS) is a severe, potentially life-threatening delayed hypersensitivity drug reaction characterised by a triad of extensive skin rash, fever, lymphadenopathy, and multi-organ involvement with eosinophilia.
Onset: Characteristically delayed — symptoms appear 2–6 weeks after initiation of the offending drug (much later than typical drug rashes).
Common causative drugs:
  • Anticonvulsants: phenytoin, phenobarbital, valproate, lamotrigine, carbamazepine
  • Antibiotics: sulfonamides, dapsone, minocycline, vancomycin, isoniazid
  • Allopurinol, abacavir, nevirapine
Clinical features:
  • High-grade fever (38–40°C)
  • Extensive maculopapular erythematous rash (may progress to exfoliative dermatitis)
  • Facial oedema (characteristic, especially periorbital)
  • Lymphadenopathy
  • Eosinophilia (hallmark)
  • Organ involvement: hepatitis (most common), interstitial nephritis, pneumonitis, myocarditis, encephalitis
Pathogenesis: Altered drug metabolism → reactive metabolite accumulation → immune-mediated T-cell activation; reactivation of latent herpesviruses (HHV-6, EBV, CMV) implicated.
Diagnosis: Clinical + RegiSCAR scoring criteria; eosinophilia + atypical lymphocytes on blood film; elevated liver enzymes.
Management: Immediate withdrawal of offending drug; systemic corticosteroids (prednisone 1–2 mg/kg/day); supportive care; monitor for organ dysfunction for weeks as condition may persist or worsen after drug withdrawal.
Prognosis: Mortality ~10% primarily from hepatic failure. — Goldman-Cecil Medicine, International Edition

2. Non-Cirrhotic Portal Fibrosis (NCPF) with Portal Hypertension, Oesophageal Varices & Pulmonary Aspergillosis

Non-Cirrhotic Portal Fibrosis (NCPF)

Definition: A distinct clinicopathological entity characterised by portal fibrosis and intrahepatic portal hypertension without cirrhosis. Also called Idiopathic Portal Hypertension (IPH) or Hepatoportal Sclerosis.
Epidemiology: Common in South Asia (India) and developing countries; typically affects young adults from lower socioeconomic backgrounds.
Aetiology: Multifactorial — repeated gut-derived bacterial infections, arsenic exposure, immunological mechanisms, and thrombophilic states have been implicated.
Pathology: Fibrosis and obliteration of small intrahepatic portal vein radicles → pre-sinusoidal block → portal hypertension with preserved hepatocellular function (distinguishes it from cirrhosis).
Portal Hypertension & Oesophageal Varices:
  • Portal vein pressure elevated (>12 mmHg); collaterals form → oesophageal & gastric varices
  • Splenomegaly (often massive) + hypersplenism (pancytopenia)
  • Ascites is less common than in cirrhosis
  • Oesophageal varices are the major complication causing recurrent upper GI bleeding
  • Liver function is relatively preserved until late stages
Management of varices: Non-selective beta-blockers (propranolol) for primary prophylaxis; endoscopic variceal ligation (EVL) or sclerotherapy for acute bleeds; TIPS in refractory cases; portosystemic shunt surgery (splenorenal shunt) may be curative in selected patients.

Pulmonary Aspergillosis (concurrent or complicating)

Definition: Fungal infection by Aspergillus fumigatus (most common). The clinical form depends on the host immune status:
  • Allergic Bronchopulmonary Aspergillosis (ABPA): In asthmatics/CF patients
  • Chronic Pulmonary Aspergillosis (CPA): In mildly immunocompromised or structurally abnormal lungs
  • Invasive Pulmonary Aspergillosis (IPA): In profoundly immunocompromised (neutropenic) hosts — most severe
In NCPF context: Splenomegaly-driven hypersplenism, possible immunosuppression from treatment, or concurrent conditions (e.g., steroid use, underlying TB-damaged lungs) can predispose to CPA or IPA.
Clinical features: Haemoptysis, cough, cavitating lung lesions (CPA); fever, pleuritic chest pain, haemoptysis (IPA); "halo sign" on CT chest in IPA.
Diagnosis: CT chest (halo sign / air-crescent sign); serum galactomannan; beta-D-glucan; bronchoscopy with BAL; culture.
Management: Voriconazole (drug of choice for IPA); isavuconazole or liposomal amphotericin B as alternatives.

3. Guillain-Barré Syndrome (GBS)

Definition: An acute, immune-mediated polyradiculoneuropathy — the most common cause of acute flaccid paralysis worldwide.
Pathogenesis: Molecular mimicry following infection (most commonly Campylobacter jejuni, also CMV, EBV, Zika, COVID-19) → autoantibodies against peripheral nerve gangliosides (GM1, GD1b) → demyelination (AIDP) or axonal damage (AMAN/AMSAN).
Clinical features:
  • Ascending symmetrical weakness beginning in legs, progressing upward over days–weeks
  • Areflexia (hallmark)
  • Sensory symptoms (tingling, numbness in glove-and-stocking distribution)
  • Autonomic dysfunction (labile BP, cardiac arrhythmias, ileus, urinary retention) — a dangerous feature
  • Respiratory failure in 20–30% (requires ICU monitoring)
  • Miller Fisher Variant: ophthalmoplegia + ataxia + areflexia (anti-GQ1b antibodies)
Diagnosis:
  • CSF: cytoalbuminous dissociation (elevated protein with normal or near-normal cell count)
  • Nerve conduction studies: prolonged distal latencies, reduced velocities, conduction block (AIDP)
  • Anti-ganglioside antibodies
Management:
  • IVIG (2 g/kg over 5 days) or plasmapheresis — equally effective; do not combine
  • Supportive care: ventilatory support, DVT prophylaxis, pain management, physiotherapy
  • Steroids: not beneficial in GBS
  • Monitoring: FVC (forced vital capacity) serially; intubate if FVC <15–20 mL/kg
Prognosis: 85% recover full function; 5–10% residual disability; 3–5% mortality. — Adams and Victor's Principles of Neurology, 12th Ed.

4. Myasthenia Gravis (MG)

Definition: A chronic autoimmune neuromuscular junction disorder characterised by fatigable muscle weakness.
Pathogenesis: Autoantibodies (primarily anti-AChR IgG; less commonly anti-MuSK, anti-LRP4) attack the postsynaptic neuromuscular junction by:
  1. Direct blockade of acetylcholine binding
  2. Cross-linking and internalisation/degradation of AChRs
  3. Complement-mediated lysis of the postsynaptic membrane
Subtypes (Goldman-Cecil):
  • AChR antibody-positive, early-onset (F > M, thymic hyperplasia)
  • AChR antibody-positive, late-onset (M > F, atrophic thymus; onset after age 50)
  • MuSK antibody-positive (predominantly female; predominantly bulbar/facial weakness)
  • Thymoma-associated (~10% of patients; deficient AIRE → loss of immune tolerance)
  • Seronegative (~15%; no detectable antibodies)
Clinical features:
  • Ocular: ptosis + diplopia (most common initial presentation)
  • Bulbar: dysarthria, dysphagia, nasal regurgitation
  • Limb weakness: proximal > distal; fatigable on repetitive use
  • Myasthenic crisis: severe respiratory failure requiring ventilation — precipitated by infection, surgery, certain drugs (aminoglycosides, fluoroquinolones, beta-blockers)
Diagnosis:
  • Edrophonium (Tensilon) test (now less commonly used)
  • Ice pack test (for ptosis)
  • Anti-AChR antibodies (sensitivity ~85% in generalised MG)
  • Anti-MuSK antibodies (for seronegative cases)
  • Repetitive nerve stimulation: decremental response >10%
  • Single-fibre EMG: most sensitive test (jitter)
  • CT chest: thymic abnormality
Management:
  • Symptomatic: Pyridostigmine (AChE inhibitor) — first-line
  • Immunosuppression: Prednisolone ± azathioprine (long-term); mycophenolate, cyclosporin, tacrolimus as alternatives
  • Acute crisis: IVIG or plasmapheresis
  • Thymectomy: recommended for all thymoma-associated MG and for non-thymomatous AChR-positive patients under age 65 — improves remission rates
  • Complement inhibitor: Eculizumab (for refractory anti-AChR positive MG)
— Goldman-Cecil Medicine, International Edition

5. Posterior Reversible Encephalopathy Syndrome (PRES)

Definition: A clinico-radiological syndrome of neurological dysfunction characterised by headache, seizures, altered consciousness, and visual disturbances, with reversible vasogenic cerebral oedema predominantly affecting the posterior cerebral white matter.
Pathogenesis: Failure of cerebrovascular autoregulation (from sudden/severe hypertension or endothelial dysfunction) → breakthrough hyperperfusion → vasogenic oedema predominantly in parieto-occipital regions (watershed zones, relatively poor sympathetic innervation posteriorly).
Common precipitants:
  • Hypertensive emergency (most common; BP typically systolic >195 mmHg)
  • Eclampsia / pre-eclampsia
  • Immunosuppressive drugs: tacrolimus, cyclosporin, bevacizumab
  • Cytotoxic chemotherapy
  • Sepsis / thrombotic microangiopathy (TTP, HUS)
  • Renal disease
Clinical features:
  • Headache (often severe, acute onset)
  • Seizures (in up to 90% of patients)
  • Visual disturbances: cortical blindness, visual field defects, hallucinations, Balint syndrome
  • Altered mental status / confusion
  • Focal neurological deficits (less common)
  • Papilloedema, retinal haemorrhages (in hypertensive cases)
Imaging (MRI):
  • T2/FLAIR hyperintensity in parieto-occipital white matter (bilateral, symmetric)
  • DWI: typically ADC map increased (vasogenic not cytotoxic oedema — key distinction from infarct)
  • CT: bilateral posterior hypodensity
Management:
  • Treat underlying cause urgently (controlled BP reduction in hypertensive PRES — aim ~20–25% reduction in first hour; avoid rapid overcorrection)
  • Anti-epileptics for seizure control
  • Discontinue offending drug if drug-induced
  • Supportive care
Prognosis: Generally reversible (imaging and clinical normalisation over days–weeks) if treated promptly. Delayed treatment may result in permanent infarction. — Adams and Victor's Principles of Neurology, 12th Ed.; Brenner & Rector's The Kidney

6. Acute Non-Haemorrhagic Infarct in the Left Parietal Lobe

Definition: Ischaemic (non-haemorrhagic) stroke resulting from occlusion of a blood vessel supplying the left parietal lobe, leading to neuronal death without macroscopic bleeding.
Vascular territory: Usually involves branches of the left middle cerebral artery (MCA) — specifically the parietal (postcentral/superior parietal) branches; occasionally posterior cerebral artery (PCA) involvement.
Pathophysiology: Arterial occlusion (thromboembolism from cardiac source, large-vessel atherosclerosis, or small-vessel lacunar disease) → ischaemic penumbra → neuronal death in the core zone within hours.
Clinical features of left parietal lobe infarction:
  • Contralateral (right-sided) sensory loss — cortical sensory modalities: two-point discrimination, stereognosis, graphaesthesia
  • Contralateral hemineglect (usually less severe than right parietal; right hemisphere dominant for spatial attention)
  • Dominant hemisphere (left) specific deficits:
    • Gerstmann syndrome: acalculia, agraphia, finger agnosia, left-right disorientation
    • Ideomotor apraxia: inability to perform learned motor acts on command
    • Conduction aphasia (if supramarginal/angular gyrus involved): fluent speech with poor repetition and paraphasic errors
  • Contralateral lower facial weakness if adjacent sensorimotor strip involved
DWI-MRI: Restricted diffusion (bright DWI, dark ADC map) — confirms acute ischaemic infarct; distinguishes from PRES or demyelination.
Management (acute ischaemic stroke):
  • IV thrombolysis (Alteplase/Tenecteplase): within 4.5 hours of onset (if no contraindications)
  • Mechanical thrombectomy: up to 24 hours for large vessel occlusion (LVO)
  • Antiplatelet therapy (aspirin 300 mg loading, then dual antiplatelet short-term, then monotherapy)
  • Anticoagulation if cardioembolic (AF) — timing depends on infarct size
  • BP management, glycaemic control, temperature management
  • Stroke unit care + early rehabilitation (physiotherapy, OT, speech therapy)
Secondary prevention: Based on aetiology — anticoagulation (AF), statins + antiplatelets (atherosclerosis), blood pressure control.

7. Peripheral Neuropathy in Known Case of Rheumatoid Arthritis (RA)

Prevalence: Peripheral neuropathy occurs in 1–10% of RA patients clinically; electrophysiological evidence of neuropathy may be found in up to 57%.
Mechanisms and types (Bradley & Daroff's Neurology):
TypeMechanismFeatures
Compression/Entrapment neuropathyJoint deformity, rheumatoid nodulesCarpal tunnel (median nerve), tarsal tunnel (anterior tibial nerve) — most common; responsive to splinting/injection/surgery
Chronic symmetric sensory polyneuropathyOcclusive vasculopathy / low-grade vasculitisPatchy stocking-glove dysaesthesias & sensory loss; not associated with severe RA; good prognosis; no specific treatment
Mononeuritis multiplexSystemic rheumatoid vasculitisAcute onset; asymmetric; multiple individual nerve territories; seen with severe, longstanding RA
Distal symmetrical sensorimotor polyneuropathyVasculitisSeen in severe RA with systemic vasculitis
Vasculitic neuropathy (most severe form):
  • Occurs in severe longstanding RA with joint deformity, nodules, cutaneous vasculitic lesions
  • Elevated ESR, RF; low C4 complement
  • Nerve biopsy: necrotising vasculitis
  • 5-year survival: ~60%
  • Treatment: High-dose prednisolone + cyclophosphamide
Drug-induced neuropathy: Methotrexate (rarely), leflunomide, gold salts — must be considered in differential.
Diagnosis: Nerve conduction studies + EMG; nerve ± muscle biopsy for suspected vasculitis; ESR, RF, CRP, complement levels.
— Bradley and Daroff's Neurology in Clinical Practice; Goldman-Cecil Medicine

8. Hodgkin Lymphoma (HL)

Definition: A malignant lymphoma arising from germinal centre or post-germinal centre B cells, characterised by the pathognomonic Reed-Sternberg (RS) cells in an inflammatory background.
Epidemiology: Bimodal age distribution — peak at 15–35 years and again after age 55. Slightly more common in males. Association with EBV (particularly mixed cellularity subtype).
WHO Classification:
  1. Classical HL (95%):
    • Nodular Sclerosis (most common, ~70%): young adults, mediastinal mass, fibrous bands + lacunar cells
    • Mixed Cellularity (~25%): older patients, EBV-associated, RS cells in mixed inflammatory background
    • Lymphocyte-Rich (rare): good prognosis
    • Lymphocyte-Depleted (rare): poor prognosis, HIV-associated
  2. Nodular Lymphocyte Predominant HL (NLPHL, ~5%): "Popcorn cells" (LP cells); CD20+; indolent; low risk of transformation
Clinical features:
  • Painless cervical/supraclavicular lymphadenopathy (most common presentation)
  • Mediastinal mass (widened mediastinum on CXR — "cotton wool" appearance)
  • Splenomegaly, hepatomegaly
  • B symptoms (present in ~40%): fever >38°C, drenching night sweats, unexplained weight loss >10% in 6 months
  • Alcohol-induced lymph node pain (pathognomonic but uncommon)
  • Pruritis
Diagnosis:
  • Excisional lymph node biopsy: RS cells (large binucleate cells, "owl eye" nucleoli), CD15+, CD30+, CD45−
  • Staging: CT chest/abdomen/pelvis + PET-CT (Ann Arbor staging I–IV)
  • Bone marrow biopsy for stage III–IV
Treatment:
  • Stage I–II (favourable): ABVD × 2–4 cycles ± involved-field radiotherapy
  • Stage III–IV or unfavourable: ABVD × 6 cycles (or escalated BEACOPP in high-risk)
  • Relapsed/refractory: Brentuximab vedotin (anti-CD30 ADC), checkpoint inhibitors (pembrolizumab/nivolumab), autologous SCT
  • Cure rates: up to 80% — one of the most curable malignancies. — Swanson's Family Medicine Review; Cummings Otolaryngology

9. Inflammatory Bowel Disease — Crohn's Disease

Definition: A chronic, relapsing-remitting, idiopathic transmural granulomatous inflammation that can affect any part of the GI tract from mouth to anus, most commonly the terminal ileum and proximal colon. — Goldman-Cecil Medicine
Epidemiology: Incidence ~20 per 100,000 person-years in North America; peak onset 2nd–4th decade (second peak in 7th decade); no clear gender predominance; higher incidence in White, Ashkenazi Jewish populations; increasing globally.
Pathobiology: Genetic predisposition (NOD2/CARD15 mutations most studied) + dysregulated immune response to gut microbiome + environmental triggers (cigarette smoking worsens Crohn's; NSAIDs exacerbate disease).
Distinguishing features from Ulcerative Colitis:
FeatureCrohn's DiseaseUlcerative Colitis
LocationEntire GI tract (skip lesions)Colon only (continuous, from rectum)
DepthTransmuralMucosal/submucosal
GranulomasYes (non-caseating)No
SmokingWorsensProtective
Rectal involvement50%Always
Perianal diseaseCommonRare
Clinical features:
  • Chronic diarrhoea (non-bloody more typical than UC), abdominal pain (RLQ most common)
  • Malabsorption, weight loss, nutritional deficiencies (B12, folate, iron, fat-soluble vitamins)
  • Complications: Strictures, fistulae (enteroenteric, enterovesical, enterocutaneous, perianal), abscesses, perforation, obstruction
  • Extra-intestinal manifestations: Erythema nodosum, pyoderma gangrenosum, uveitis/episcleritis, primary sclerosing cholangitis (more UC), peripheral arthropathy, ankylosing spondylitis, clubbing
Diagnosis: Ileocolonoscopy with biopsies (transmural inflammation, non-caseating granulomas); CT/MRI enterography (bowel wall thickening, skip lesions, fistulae); capsule endoscopy for small bowel; elevated CRP, faecal calprotectin.
Management:
  • Induction: Corticosteroids (prednisolone, budesonide for ileocaecal), exclusive enteral nutrition
  • Maintenance: Azathioprine/6-MP, methotrexate; Biologics: infliximab, adalimumab (anti-TNF), vedolizumab (anti-α4β7 integrin), ustekinumab (anti-IL-12/23), risankizumab
  • Surgery: For refractory disease, strictures, fistulae, abscesses — not curative (recurrence common post-resection); ileostomy/colostomy as needed

10. Lipoma

Definition: A benign mesenchymal tumour composed of mature adipocytes (fat cells), representing the most common soft tissue tumour in adults.
Epidemiology: Incidence peaks in the 4th–5th decades; slightly more common in males; can be solitary or multiple (multiple lipomas may indicate familial lipomatosis).
Locations: Most common in the subcutaneous tissue of the posterior neck, upper back, shoulders, proximal extremities, and abdominal wall. Can also occur in deeper locations (intermuscular, intramuscular, retroperitoneal, parosteal, epidural).
Clinical features:
  • Soft, fluctuant, mobile, non-tender subcutaneous mass
  • Typically 1–5 cm (larger "giant lipomas" >10 cm described)
  • Skin overlying normal
  • No constitutional symptoms
  • Slow growing, rarely symptomatic unless compressing adjacent structures (nerve compression → pain/weakness)
Variants:
  • Angiolipoma: painful, vascular component; common in forearms of young men
  • Fibrolipoma: fibrous stroma; firmer consistency
  • Spindle cell/Pleomorphic lipoma: benign; posterior neck/shoulder in older males; may mimic liposarcoma on imaging
  • Hibernoma: composed of brown fat; rare
  • Lipomatosis: diffuse infiltration of a body region (e.g., Madelung disease — symmetric cervical lipomatosis)
Diagnosis:
  • Clinical in most cases (characteristic soft, mobile, subcutaneous lump)
  • Ultrasound: hyperechoic, compressible lesion with internal striations
  • MRI: follows fat signal on all sequences (T1 bright, T2 bright, suppressed on fat-sat) — needed for deep lipomas to exclude liposarcoma
  • Biopsy/histology: mature adipocytes without atypia — only when diagnosis uncertain
Management:
  • Most require no treatment — observation acceptable
  • Surgical excision for: symptomatic lipomas, cosmetic concern, diagnostic uncertainty, or rapid growth
  • Recurrence rare with complete excision; liposarcoma must always be excluded for deep-seated or large (>5 cm) lesions

11. Epididymo-orchitis

Definition: Inflammation of the epididymis (epididymitis) often extending to the testis (orchitis), constituting epididymo-orchitis — the most common cause of the acute scrotum in adult men.
Aetiology (age-dependent):
Age GroupCommon Pathogens
<35 years (sexually active)Chlamydia trachomatis (most common), Neisseria gonorrhoeae
>35 years / childrenE. coli, Klebsiella, Pseudomonas (urinary tract organisms)
Any ageMycobacterium tuberculosis (TB epididymo-orchitis — important in endemic regions), mumps virus (orchitis without epididymitis)
ImmunocompromisedCryptococcus, Brucella, fungal
Clinical features:
  • Unilateral scrotal pain and swelling (typically gradual onset over days, vs. sudden onset in testicular torsion)
  • Tender, enlarged epididymis ± testis
  • Prehn's sign: relief of pain with elevation of scrotum (classically positive in epididymo-orchitis; negative in torsion) — not fully reliable
  • Urethral discharge, dysuria, frequency (if STI or UTI-associated)
  • Fever, systemic features in severe cases
  • Reactive hydrocele may develop
Investigations:
  • Urine microscopy & culture (midstream urine)
  • Urethral swab / NAAT (PCR) for Chlamydia and Gonorrhoea
  • Scrotal Doppler ultrasound: increased blood flow to epididymis/testis (distinguishes from torsion — decreased flow); confirms diagnosis; excludes abscess
  • FBC, CRP; consider STI screen (HIV, syphilis)
  • Radionuclide scan or surgical exploration if torsion cannot be excluded
Management:
  • STI-associated (< 35 yrs): Ceftriaxone 500 mg IM (single dose) + Doxycycline 100 mg BD × 10–14 days (covers both gonorrhoea and chlamydia); per local STI guidelines
  • Enteric organism (> 35 yrs): Ciprofloxacin 500 mg BD × 10–14 days OR ofloxacin; treat underlying UTI
  • TB epididymo-orchitis: Standard anti-TB therapy (6-month RHEZ regimen)
  • Supportive: scrotal elevation, analgesia (NSAIDs), rest
  • Surgical drainage for abscess formation; orchiectomy if testicular necrosis
Complications: Infertility (bilateral orchitis), testicular atrophy, chronic epididymitis, abscess, reactive hydrocele.
Sources: Goldman-Cecil Medicine International Edition; Adams and Victor's Principles of Neurology 12e; Bradley and Daroff's Neurology in Clinical Practice; Brenner and Rector's The Kidney; Murray & Nadel's Textbook of Respiratory Medicine; Swanson's Family Medicine Review; Cummings Otolaryngology Head and Neck Surgery — supplemented with standard clinical knowledge from Harrison's Principles of Internal Medicine and established clinical guidelines.

disease hypertension, diabetes mellistus

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I now have rich textbook data from both Fuster & Hurst's The Heart and Rosen's Emergency Medicine to compile comprehensive briefs on both diseases. Here is the complete output:

Disease Briefs

1. Hypertension (HTN)

Definition

A chronic medical condition characterised by persistently elevated arterial blood pressure, conferring increased risk for cardiovascular, cerebrovascular, renal, and retinal disease.

Classification (ACC/AHA 2017 Guideline)

CategorySystolic BP (SBP)Diastolic BP (DBP)
Normal< 120 mmHgand< 80 mmHg
Elevated120–129 mmHgand< 80 mmHg
Stage 1 HTN130–139 mmHgor80–89 mmHg
Stage 2 HTN≥ 140 mmHgor≥ 90 mmHg
Hypertensive Crisis> 180 mmHgand/or> 120 mmHg
The older JNC 7 threshold of ≥ 140/90 mmHg for HTN is still used widely in many countries and guidelines (ESC/ESH 2018).

Epidemiology

  • Affects ~31% of adults globally (1.39 billion people); prevalence rising with aging populations and increasing obesity.
  • Leading modifiable risk factor for CVD, accounting for 22% of CVD population-attributable fraction — greater than high cholesterol, tobacco, or diabetes.
  • For every 20/10 mmHg increase in SBP/DBP, mortality from coronary heart disease doubles.
  • Control rates remain poor: < 50% in the USA, as low as 8–14% in low- and middle-income countries. — Fuster & Hurst's The Heart, 15th Ed.

Types

  1. Primary (Essential) Hypertension (~90–95%): No identifiable cause; multifactorial (genetic + environmental).
  2. Secondary Hypertension (~5–10%): Identifiable, potentially reversible cause.
Causes of Secondary Hypertension:
  • Renal disease (most common cause in adults): chronic kidney disease, renovascular HTN (renal artery stenosis)
  • Endocrine: Primary hyperaldosteronism (Conn syndrome), phaeochromocytoma, Cushing syndrome, hyperthyroidism, hyperparathyroidism
  • Obstructive sleep apnoea
  • Coarctation of the aorta
  • Drug-induced: NSAIDs, oral contraceptives, corticosteroids, sympathomimetics, cocaine

Pathophysiology

  • Blood pressure = Cardiac Output (CO) × Total Peripheral Resistance (TPR)
  • In primary HTN: CO is typically normal; TPR is elevated (often as an autoregulatory response)
  • Key mechanisms:
    • Renin-Angiotensin-Aldosterone System (RAAS) activation → sodium & water retention → increased CO and vasoconstriction
    • Sympathetic nervous system overactivity → vasoconstriction, increased heart rate and CO
    • Endothelial dysfunction → reduced nitric oxide → impaired vasodilation
    • Vascular remodelling → structural thickening of arterial walls → sustained increased TPR
    • Chronic HTN shifts the autoregulatory curve to higher BP ranges → tolerance of high BP but risk of hypoperfusion with rapid reduction

Modifiable Risk Factors

High sodium intake, obesity/overweight, physical inactivity, excessive alcohol, smoking, high-fat diet, psychological stress.

Clinical Features

Most patients are asymptomatic — HTN is the "silent killer." Symptoms, when present, relate to end-organ damage:
  • Headache (typically occipital, morning)
  • Visual blurring, epistaxis (severe HTN)
  • Features of end-organ damage (EOD):
    • Heart: LVH, angina, MI, heart failure
    • Brain: Stroke, TIA, hypertensive encephalopathy, PRES, dementia
    • Kidneys: Proteinuria, CKD, renal failure
    • Eyes: Hypertensive retinopathy (Keith-Wagener-Barker grading I–IV: arteriolar narrowing → AV nipping → flame haemorrhages/exudates → papilloedema)
    • Aorta: Dissection

Hypertensive Crisis

  • Hypertensive Urgency: BP > 180/120 mmHg, no acute EOD → oral agents, gradual reduction over 24–48 h
  • Hypertensive Emergency: Severe elevation + acute EOD (STEMI, aortic dissection, acute kidney injury, hypertensive encephalopathy, pulmonary oedema, eclampsia) → IV agents in ICU, controlled reduction (not more than 20–25% in first hour; target 160/100 mmHg in first hour)
    • IV agents of choice: Labetalol, nicardipine, sodium nitroprusside (used cautiously), hydralazine (eclampsia)

Investigations

  • Urinalysis, serum creatinine & eGFR (renal involvement)
  • Electrolytes (hypokalaemia → hyperaldosteronism)
  • Fasting glucose, lipid profile (CV risk stratification)
  • ECG (LVH: Sokolow-Lyon criteria), echocardiogram
  • Fundoscopy (retinopathy grading)
  • 24-hour urinary catecholamines/metanephrines (phaeochromocytoma screen)
  • Renal artery Doppler / aldosterone:renin ratio (secondary HTN work-up)

Management

Lifestyle Modifications (All patients)

  • DASH diet (reduced sodium < 2.3 g/day, increased K, Ca, Mg)
  • Weight loss (1 mmHg reduction per 1 kg weight loss)
  • Regular aerobic exercise (30 min/day, most days)
  • Limit alcohol (< 2 drinks/day men, < 1 drink/day women)
  • Smoking cessation

Pharmacological Treatment

BP Targets (AHA/ACC 2017):
  • General population with CVD risk: < 130/80 mmHg
  • Diabetes or CKD: < 130/80 mmHg
  • Elderly (≥ 65 yrs, ambulatory): < 130 mmHg systolic if tolerated
First-line Drug Classes (monotherapy or combination):
ClassExamplesPreferred In
ACE Inhibitors (ACEi)Enalapril, Ramipril, LisinoprilDiabetes, CKD with proteinuria, HF
ARBsLosartan, Valsartan, TelmisartanACEi-intolerant, Diabetes, CKD
Calcium Channel Blockers (CCB)Amlodipine, NifedipineElderly, Isolated systolic HTN, Black patients
Thiazide/Thiazide-like diureticsHydrochlorothiazide, Chlorthalidone, IndapamideBlack patients, Elderly, isolated systolic HTN
Beta-blockersMetoprolol, Bisoprolol, CarvedilolPost-MI, HFrEF, Angina (not first-line for uncomplicated HTN)
Combination Therapy: Most patients with Stage 2 HTN require ≥ 2 agents. Standard combination: ACEi/ARB + CCB ± thiazide diuretic.
Resistant HTN (uncontrolled on ≥ 3 agents including diuretic):
  • Add mineralocorticoid receptor antagonist (spironolactone) — highly effective
  • Exclude secondary causes, non-adherence, white coat phenomenon
  • Refractory HTN (≥ 5 agents): consider renal denervation

Prognosis

Effective BP control significantly reduces: stroke risk by ~35–40%, MI by ~20–25%, heart failure by ~50%, CKD progression. — Fuster & Hurst's The Heart, 15th Ed.; Miller's Anesthesia, 10th Ed.

2. Diabetes Mellitus (DM)

Definition

A group of metabolic disorders characterised by chronic hyperglycaemia resulting from defects in insulin secretion, insulin action, or both, leading to disturbances in carbohydrate, fat, and protein metabolism and long-term multi-organ complications.

Classification (ADA)

TypeKey Feature
Type 1 DMAutoimmune destruction of pancreatic β-cells → absolute insulin deficiency
Type 2 DMProgressive insulin resistance + relative insulin deficiency; β-cell exhaustion
Gestational DM (GDM)Glucose intolerance first detected in pregnancy
Other specific typesMODY, LADA, secondary (chronic pancreatitis, CF, Cushing, drugs)
PrediabetesIFG (FPG 100–125 mg/dL) or IGT (2-hr PG 140–199 mg/dL) or HbA1c 5.7–6.4%

Epidemiology

  • ~537 million adults affected worldwide (IDF 2021); projected to reach 783 million by 2045
  • Type 2 DM accounts for ~90–95% of all cases
  • Peak incidence: 2nd–4th decade for T1DM; 4th–6th decade for T2DM
  • Strong association with obesity, sedentary lifestyle, family history

Pathophysiology

Type 1 DM

  • Autoimmune destruction of β-cells, mediated by T-cells (CD4+ and CD8+)
  • Autoantibodies: anti-GAD65, anti-IA2, anti-insulin (IAA), anti-ZnT8
  • Genetic susceptibility: HLA-DR3, HLA-DR4 (> 90% of patients)
  • Results in absolute insulin deficiency → uncontrolled lipolysis and ketogenesis → DKA
  • Late stage: near-total absence of β-cells; α-cells (glucagon) preserved

Type 2 DM

  • Dual defect: Peripheral insulin resistance (muscle/adipose) + progressive β-cell failure
  • Insulin resistance: defects in insulin receptor signalling; impaired muscle glycogen synthesis; adipokine dysregulation (↑ TNF-α, ↑ free fatty acids)
  • Compensatory hyperinsulinaemia initially → β-cell exhaustion over years → relative insulin deficiency
  • Glucotoxicity and lipotoxicity accelerate β-cell decline
  • Incretins (GLP-1, GIP) impaired in T2DM → reduced glucose-stimulated insulin secretion
  • No HLA association; no autoantibodies; ketosis rare — Rosen's Emergency Medicine

Diagnostic Criteria (ADA 2021)

Any ONE of the following:
  1. HbA1c ≥ 6.5% (preferred confirmatory test)
  2. Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) — fasting = no caloric intake ≥ 8 h
  3. 2-hour plasma glucose ≥ 200 mg/dL during 75 g OGTT
  4. Random plasma glucose ≥ 200 mg/dL + classic symptoms (polyuria, polydipsia, unexplained weight loss)
In asymptomatic patients, two abnormal tests from two separate occasions are required for confirmation.

Clinical Features

Type 1 DM:
  • Acute onset, typically in children/young adults
  • Classic triad: Polyuria, Polydipsia, Polyphagia + weight loss
  • Fatigue, blurred vision
  • Prone to Diabetic Ketoacidosis (DKA): Nausea, vomiting, abdominal pain, Kussmaul breathing, fruity breath, altered consciousness
Type 2 DM:
  • Often asymptomatic for years (diagnosed on routine screening)
  • Same triad when symptomatic, but milder
  • Recurrent infections (skin, urinary, candidal)
  • Acanthosis nigricans (insulin resistance marker)
  • Prone to Hyperosmolar Hyperglycaemic State (HHS) rather than DKA

Complications

Microvascular

ComplicationFeatures
Diabetic NephropathyMicroalbuminuria → proteinuria → declining GFR → ESRD; leading cause of CKD worldwide
Diabetic RetinopathyNon-proliferative (microaneurysms, haemorrhages, exudates) → Proliferative (neovascularisation, vitreous haemorrhage, traction detachment) → Blindness; leading cause of blindness in working-age adults
Diabetic NeuropathyDistal symmetric polyneuropathy (most common); autonomic neuropathy (gastroparesis, orthostatic hypotension, erectile dysfunction, diabetic cystopathy); mononeuropathies; Charcot neuroarthropathy

Macrovascular

  • Coronary artery disease (CAD): 2–4× higher risk; often silent MI
  • Cerebrovascular disease: Stroke
  • Peripheral arterial disease (PAD): Claudication, diabetic foot, amputation

Other Complications

  • Diabetic foot: Neuropathy + ischaemia + infection → ulceration → amputation (15× higher risk)
  • Increased susceptibility to infections (TB, UTIs, fungal)
  • DKA (T1DM > T2DM): Hyperglycaemia + ketosis + metabolic acidosis; triggers — infection, missed insulin, surgery
  • HHS (T2DM): Extreme hyperglycaemia (> 600 mg/dL) + severe dehydration, hyperosmolality, no significant ketosis; high mortality (10–20%)

Investigations

  • HbA1c (glycaemic control over 3 months); target < 7% (53 mmol/mol) for most
  • FPG, OGTT (diagnosis and monitoring)
  • Urinalysis + spot urine ACR (microalbuminuria)
  • Serum creatinine, eGFR
  • Lipid profile (cardiovascular risk)
  • Fundoscopy (annual retinal screening)
  • Foot examination (annual — ABI, monofilament sensation)
  • ECG / cardiac workup (silent ischaemia)
  • C-peptide + autoantibodies (type classification)

Management

Type 1 DM

  • Insulin therapy (lifelong) — basal-bolus regimen:
    • Basal: long-acting insulin (glargine, detemir, degludec)
    • Bolus: rapid-acting insulin (lispro, aspart, glulisine) with meals
  • Continuous subcutaneous insulin infusion (CSII/pump)
  • Carbohydrate counting + sick day rules
  • Islet cell transplantation (experimental/select centres)

Type 2 DM — Stepwise Approach

Step 1 — Lifestyle Modification (all patients):
  • Medical nutrition therapy (MNT): caloric restriction, low-glycaemic-index diet
  • Physical activity (≥150 min/week moderate-intensity aerobic)
  • Weight loss (7% body weight target)
Step 2 — Pharmacotherapy:
Drug ClassMechanismKey Notes
Metformin↓ Hepatic glucose production (AMPK activation)First-line; weight-neutral; cheap; contraindicated in eGFR < 30; may cause B12 deficiency
SGLT2 Inhibitors (Empagliflozin, Dapagliflozin, Canagliflozin)↓ Renal glucose reabsorptionCV and renal protective; weight loss; preferred in HFrEF and CKD; risk: DKA, UTI, Fournier's gangrene
GLP-1 Receptor Agonists (Semaglutide, Liraglutide, Dulaglutide)↑ Glucose-dependent insulin; ↓ glucagon; slows gastric emptyingCV protective; significant weight loss; preferred in obesity; injectable (semaglutide also oral)
DPP-4 Inhibitors (Sitagliptin, Saxagliptin)↑ Endogenous GLP-1Weight-neutral; well-tolerated
Sulfonylureas (Glibenclamide, Glipizide, Gliclazide)↑ Insulin secretion from β-cellsHypoglycaemia risk; weight gain; inexpensive
Thiazolidinediones (TZDs) (Pioglitazone)↑ Insulin sensitivity (PPAR-γ)CV benefit in some; weight gain; fluid retention; contraindicated in HF
InsulinReplaces/supplements insulinRequired in T1DM; may be needed in T2DM (progressive β-cell failure)
Current Priority (ADA 2024):
  • In patients with established CVD or high CV risk: SGLT2i or GLP-1 RA regardless of HbA1c
  • In patients with CKD: SGLT2i preferred (renoprotective)
  • In patients with HFrEF: SGLT2i preferred
Glycaemic Targets:
  • HbA1c < 7% for most adults
  • < 8% for elderly, frail, or those with frequent hypoglycaemia
  • < 6.5% if achievable without hypoglycaemia (young, short duration)

Management of DKA

  • IV fluids (normal saline), IV insulin infusion, potassium replacement, bicarbonate (if pH < 6.9), identify and treat precipitant

Management of HHS

  • Aggressive IV fluid resuscitation, slow insulin infusion, electrolyte correction, VTE prophylaxis

Prognosis

The UKPDS showed that each 1% reduction in HbA1c is associated with 21% reduction in diabetes-related deaths, 37% reduction in microvascular complications, 14% reduction in MI. Multifactorial risk factor management (BP, lipids, glycaemia, smoking) dramatically reduces complications. — Rosen's Emergency Medicine; Textbook of Family Medicine, 9th Ed.; Fuster & Hurst's The Heart, 15th Ed.
Sources: Fuster & Hurst's The Heart 15th Ed. | Rosen's Emergency Medicine | Textbook of Family Medicine 9th Ed. | Miller's Anesthesia 10th Ed. | Goodman & Gilman's Pharmacological Basis of Therapeutics | Brenner & Rector's The Kidney
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