General and Systemic Examination

PART 1: GENERAL EXAMINATION

1. General Appearance

• Built and Nutritional Status - Assess whether the patient appears well-built, average, thin (cachectic), or obese. Note any obvious wasting of muscles.
• Decubitus / Posture - Note the position in which the patient is comfortable: orthopnoea (sitting up) in heart failure; fetal position in peritonitis; opisthotonos in tetanus/meningitis.
• Gait - If ambulatory, observe for hemiplegic gait, parkinsonian shuffling gait, ataxic gait, waddling gait, etc.
• Facies - Look for characteristic facies: moon face (Cushing's), mask face (Parkinson's), leonine facies (leprosy), myxoedema facies, acromegalic facies.
• Consciousness level - Use the Glasgow Coma Scale (GCS) if needed: eye opening (1-4), verbal response (1-5), motor response (1-6). Alert, drowsy, stuporous, comatose.
• Cooperation and behavior - Agitation, confusion, restlessness.

2. Vital Signs

A. Pulse

• Rate: Normal 60-100 beats/min in adults. Tachycardia (>100), bradycardia (<60).
• Rhythm: Regular or irregular (regularly irregular vs. irregularly irregular).
• Volume: Normal, high volume (bounding - aortic regurgitation, fever, CO₂ retention), low volume (shock, AS, tamponade).
• Character/Waveform: Pulsus bisferiens (HOCM, AR+AS), pulsus alternans (LVF), collapsing pulse (AR), plateau pulse (AS).
• Vessel wall: Thickening, tortuosity.
• Radio-radial/radio-femoral delay: Coarctation of aorta.
• Sites: Radial (routine), carotid, brachial, femoral, popliteal, dorsalis pedis, posterior tibial.

B. Blood Pressure

• Normal: <120/80 mmHg. Hypertension: ≥130/80 (ACC/AHA) or ≥140/90 mmHg.
• Measure in both arms (>10 mmHg difference suggests subclavian stenosis or aortic dissection).
• Postural hypotension: fall of ≥20 mmHg systolic or ≥10 mmHg diastolic on standing.
• Pulse pressure: normal 30-40 mmHg. Widened (AR, atherosclerosis); Narrowed (cardiac tamponade, severe AS).

C. Respiratory Rate

• Normal: 12-20 breaths/min.
• Tachypnoea (>20), bradypnoea (<12).
• Cheyne-Stokes, Kussmaul (deep acidotic breathing in DKA/renal failure), Biot's breathing.

D. Temperature

• Normal oral: 36.5-37.5°C (97.7-99.5°F).
• Fever (>38°C), Hyperpyrexia (>41°C), Hypothermia (<35°C).
• Pattern: Continuous (typhoid), remittent (TB, most infections), intermittent (malaria), hectic/septic, pel-ebstein (Hodgkin's lymphoma).

E. SpO₂ (Oxygen Saturation)

• Normal: 95-100% on room air.

F. BMI and Anthropometry

• BMI = Weight (kg) / Height² (m²). Underweight <18.5, Normal 18.5-24.9, Overweight 25-29.9, Obese ≥30.

3. Pallor

• Sites to examine: Conjunctivae (lower palpebral - most reliable), oral mucosa (tongue, hard palate), nailbeds, palmar creases.
• Grading: Mild, moderate, severe.
• Causes: Anaemia (most common), shock, cold, syncope.
• Types based on conjunctival colour: Normochromic (normal red), hypochromic (pale/white), megaloblastic (slight yellow-white).

4. Icterus (Jaundice)

• Sites to examine: Sclera (earliest - detected at bilirubin 2-3 mg/dL), under tongue (sublingual jaundice), skin.
• Types:
  • Pre-hepatic: Haemolytic - lemon yellow, pallor present, dark urine (urobilinogen), no bilirubin in urine.
  • Hepatic (hepatocellular): Orange-yellow, liver enlarged or shrunken.
  • Post-hepatic (obstructive/cholestatic): Deep greenish-yellow, pale/clay-coloured stools, dark urine (conjugated bilirubin), pruritus.

5. Cyanosis

6. Clubbing

• Grade 1: Fluctuation at nail base (obliteration of Lovibond angle).
• Grade 2: Increased curvature of nail (watch-glass/drum-stick nail).
• Grade 3: Soft tissue swelling of terminal phalanx (parrot's beak/drum-stick appearance).
• Grade 4: Periosteal new bone formation (hypertrophic pulmonary osteoarthropathy - HPOA).

• Respiratory: Bronchogenic carcinoma, lung abscess, bronchiectasis, empyema, fibrosing alveolitis.
• Cardiac: Cyanotic congenital heart disease (Fallot's tetralogy, Eisenmenger's), infective endocarditis.
• GI: Crohn's disease, ulcerative colitis, cirrhosis, malabsorption.
• Others: Thyroid acropachy, familial (benign).

7. Lymphadenopathy

• Localised lymphadenopathy: Reactive (infection in drainage area), malignant metastasis.
• Generalised lymphadenopathy: Infections (TB, HIV, EBV, CMV), haematological malignancy (lymphoma, leukaemia), autoimmune (SLE, RA), sarcoidosis.

8. Oedema

• Pitting oedema: Leave a pit on pressure (retained for >30 seconds) - cardiac, renal, hepatic, nutritional.
• Non-pitting oedema: No pit on pressure - lymphoedema, myxoedema, lipedema.
• Grading (pitting):
  • +1: Trace, up to 2mm
  • +2: Mild, 2-4mm
  • +3: Moderate, 4-6mm, pits easily
  • +4: Severe, >6mm, very deep pit, limb swollen
• Distribution: Bilateral dependent (cardiac, hypoproteinaemia), facial/periorbital (nephrotic, angioedema), sacral (bedridden patients), anasarca (generalized).

9. Dehydration

10. Skin, Hair and Nails

• Skin: Rashes, pigmentation (acanthosis nigricans, vitiligo, hyperpigmentation of Addison's), texture (thickened in myxoedema, thin in Cushing's), spider naevi, purpura, petechiae.
• Hair: Alopecia, hirsutism.
• Nails: Koilonychia (iron deficiency anaemia), leukonychia (hypoalbuminaemia), Terry's nails (cirrhosis), Lindsay's nails (CKD), splinter haemorrhages (IE, vasculitis), onycholysis (thyrotoxicosis, psoriasis).

11. Hands

• Palmar erythema: Liver disease, pregnancy, thyrotoxicosis.
• Dupuytren's contracture: Liver cirrhosis, diabetes, alcoholism.
• Asterixis (liver flap): Hepatic encephalopathy, CO₂ retention, uraemia.
• Tremor: Fine (thyrotoxicosis), intention (cerebellar), resting pill-rolling (Parkinson's).
• Thenar/hypothenar wasting: CTS, ulnar nerve palsy.

12. Head and Neck

• Eyes: Exophthalmos (Grave's), Horner's syndrome, arcus senilis, xanthelasma, scleral icterus, anaemia, argyll robertson pupil.
• Mouth: Angular stomatitis (iron deficiency), glossitis (B12/iron deficiency), gum hypertrophy (phenytoin, leukaemia), foetor hepaticus, foetor uraemicus.
• Neck: JVP (jugular venous pressure - cardiac function), thyroid gland (goitre, nodule), lymph nodes, tracheal position (deviated in pleural effusion, pneumothorax, fibrosis).

• Patient at 45°; JVP seen medial to SCM.
• Normal JVP: <3 cm above sternal angle.
• Raised JVP: CCF, tamponade, SVC obstruction.
• Kussmaul's sign: JVP rises on inspiration (constrictive pericarditis).
• Waveforms: 'a' wave (atrial contraction), 'c' wave (tricuspid closing), 'v' wave (venous filling).

PART 2: SYSTEMIC EXAMINATION

SYSTEM 1: CARDIOVASCULAR SYSTEM (CVS)

Inspection

• Shape of chest (pectus excavatum, carinatum)
• Visible apex beat (forceful in volume overload)
• Visible pulsations (parasternal heave, epigastric pulsation)
• Scars (sternotomy, thoracotomy)

Palpation

• Apex beat: Normally 5th ICS, mid-clavicular line. Displaced (cardiomegaly), heaving (pressure overload - AS, HTN), thrusting/hyperdynamic (volume overload - AR, MR).
• Parasternal heave: RV hypertrophy (mitral stenosis, pulmonary HTN).
• Thrills: Palpable murmurs (grade ≥4/6). Systolic thrill at apex (MR, VSD), aortic area (AS).
• Pericardial friction rub: Felt in pericarditis.

Percussion

• Cardiac dullness: Normally limited. Shifting dullness of cardiac border if pericardial effusion.

Auscultation

• 4 standard areas: Aortic (2nd ICS, right parasternal), Pulmonary (2nd ICS, left parasternal), Tricuspid (4th ICS, left parasternal/lower sternal), Mitral (apex).
• Heart sounds:
  • S1 (M1+T1): Mitral and tricuspid valve closure. Loud in MS, soft in MR, long PR interval.
  • S2 (A2+P2): Aortic and pulmonary closure. Wide splitting in RBBB; fixed splitting in ASD; reversed splitting in LBBB; loud P2 in pulmonary HTN.
  • S3 gallop: Ventricular filling sound - physiological in young; pathological in LVF, MR, VSD.
  • S4 gallop: Atrial kick against stiff ventricle - HTN, AS, hypertrophic cardiomyopathy.
• Murmurs: Note timing (systolic/diastolic/continuous), site, radiation, grade (Levine 1-6), quality (harsh, blowing, rumbling), dynamic auscultation (Valsalva, standing, squatting).

SYSTEM 2: RESPIRATORY SYSTEM

Inspection

• Shape of chest: Barrel chest (COPD/emphysema), kyphoscoliosis, pectus deformities.
• Movement: Symmetry of expansion, paradoxical movement (flail chest), use of accessory muscles, intercostal recession (airway obstruction in children).
• Tracheal position: Central or deviated (towards collapse, away from effusion/tension pneumothorax).
• Respiratory pattern: Rate, rhythm, depth.

Palpation

• Tracheal deviation: Two-finger technique.
• Apex beat: Shifted (mediastinal shift).
• Chest expansion: Hands placed symmetrically on either side. Normal >5 cm. Reduced unilaterally (effusion, consolidation, collapse, fibrosis); bilaterally reduced (COPD, fibrosis).
• Vocal fremitus: Vibrations palpated by ulnar surface of hand while patient says "99". Increased (consolidation), Reduced/absent (effusion, pneumothorax, collapse).

Percussion

• Begin at the apices (compare side to side), moving downward.
• Resonant: Normal lung.
• Dull: Consolidation (pneumonia), effusion (stony dull - fluid damps vibration more), collapse, fibrosis, tumour.
• Hyperresonant: Pneumothorax, emphysema.
• Shifting dullness (pleural effusion): Dull in flanks, resonant in center.
• Liver dullness (right, normally starts at 5th ICS MCL) and cardiac dullness should be noted.

Auscultation

• Normal breath sounds: Vesicular (heard over most of lung fields - soft, low-pitched, inspiratory > expiratory).
• Abnormal breath sounds:
  • Bronchial breathing: Consolidation, cavitation (loud, harsh, equal inspiration and expiration, gap between).
  • Reduced/absent: Effusion, pneumothorax, collapse.
• Added sounds:
  • Crackles (crepitations): Fine (fibrosing alveolitis, early pulmonary oedema), coarse (bronchiectasis, pneumonia, late pulmonary oedema).
  • Wheeze (rhonchi): Widespread polyphonic (asthma, COPD), monophonic (single bronchus obstruction).
  • Pleural friction rub: Dry pleurisy - creaking/leathery sound in inspiration and expiration.
• Vocal resonance: Patient says "99". Increased (bronchophony - consolidation), Whispering pectoriloquy (consolidation), Aegophony/Bleating quality (over effusion).

SYSTEM 3: GASTROINTESTINAL / ABDOMINAL SYSTEM

Inspection

• Contour: Flat, scaphoid (wasted), distended (5 F's: Fat, Fluid, Flatus, Faeces, Fetus/Foetus, Fibroid).
• Umbilicus: Central (normal), everted (ascites/umbilical hernia), displaced.
• Skin: Jaundice, striae, spider naevi, caput medusae (dilated periumbilical veins in portal HTN), Grey Turner's sign (flank bruising - retroperitoneal haemorrhage), Cullen's sign (periumbilical bruising - haemoperitoneum).
• Scars: From previous surgery.
• Visible peristalsis: Gastric outlet obstruction, intestinal obstruction.
• Pulsation: Aortic pulsation, transmitted pulsation from mass.
• Respiratory movement: Absent with peritonitis.

Palpation

• Light palpation (all 9 regions): Tenderness, guarding, rigidity.
• Deep palpation: Organomegaly, masses.
• Liver: Begin from RIF moving upward, feel for edge on inspiration. Note size (cm below costal margin), surface (smooth/nodular), edge (sharp/blunt), consistency (soft/firm/hard), tenderness.
• Spleen: Begin from RIF toward left hypochondrium. Normal not palpable. Note size (Hackett's grading 0-5), notch, texture.
• Kidneys: Bimanual ballotment technique.
• Rebound tenderness: Peritoneal irritation.
• Murphy's sign: Cessation of inspiration on pressing RUQ (acute cholecystitis).
• McBurney's point tenderness: Appendicitis.

Percussion

• Liver: Upper border (5th ICS), lower border - gives liver span (8-12 cm).
• Spleen: Traube's space (left 9th-11th ribs, midaxillary line) - normally resonant; dull if spleen enlarged.
• Ascites: Shifting dullness (>1500 mL), fluid thrill (>2000 mL, tense ascites).

Auscultation

• Bowel sounds: Normal (every 5-15 sec), absent (paralytic ileus, peritonitis), high-pitched tinkling (mechanical obstruction), hyperactive (early obstruction, diarrhoea).
• Bruit: Over aorta, renal arteries (renal artery stenosis), hepatic (hepatocellular carcinoma, AV fistula).

SYSTEM 4: CENTRAL NERVOUS SYSTEM (CNS)

Higher Mental Functions

• Orientation (time, place, person), memory (immediate, recent, remote), attention, concentration, intelligence, judgement, mood, affect.
• Mini-Mental State Examination (MMSE) if cognitive decline suspected.

Cranial Nerves (CN I-XII)

Motor System

• Bulk: Wasting, hypertrophy, fasciculations.
• Tone: Spasticity (UMN), rigidity (extrapyramidal - cogwheel/lead-pipe), hypotonia (LMN, cerebellar).
• Power: MRC scale 0-5 (0 = no movement, 5 = normal power).
• Coordination: Finger-nose test (cerebellar), heel-shin test, rapid alternating movements (dysdiadochokinesia), tandem walking.
• Reflexes (Deep tendon): Biceps (C5,6), Supinator (C5,6), Triceps (C7,8), Knee (L3,4), Ankle (S1,2). Grade 0 (absent) to 4+ (clonus).
  • Plantar reflex: Babinski sign - extensor (UMN lesion), flexor (normal).
  • Abdominal reflexes (T8-T12): Absent in UMN and obesity.

Sensory System

• Superficial sensation: Light touch, pain (pinprick), temperature.
• Deep sensation: Vibration (128 Hz tuning fork), proprioception (joint position sense), deep pain.
• Cortical sensation: Two-point discrimination, stereognosis, graphaesthesia.
• Sensory level: Important in spinal cord lesions.

Meningeal Signs

• Neck stiffness: Resistance to passive neck flexion.
• Kernig's sign: Unable to extend knee when hip is flexed at 90°.
• Brudzinski's sign: Hip and knee flex spontaneously on neck flexion.

SYSTEM 5: MUSCULOSKELETAL SYSTEM

• Look: Deformity, swelling, skin changes, muscle wasting, gait.
• Feel: Temperature, tenderness, synovial thickening, effusion, crepitus.
• Move: Active range, passive range, painful arc.
• Special tests: McMurray's (knee meniscus), Lachman's (ACL), Neer/Hawkins (shoulder impingement), FABER/FADIR (hip), Finkelstein (De Quervain's).
• Function: Activities of daily living.

SYSTEM 6: GENITOURINARY SYSTEM

• Renal angle tenderness: Costovertebral angle tenderness (pyelonephritis, renal calculi).
• Bladder: Suprapubic palpation/percussion for retention.
• Genitalia: Examined when clinically indicated.
• Peripheral oedema: Lower limb oedema from nephrotic syndrome.
• Blood pressure: Hypertension (renal cause).

SYSTEM 7: ENDOCRINE SYSTEM

• Thyroid: Inspection (swelling), palpation (from behind, ask patient to swallow - thyroid rises), percussion (retrosternal extension), auscultation (bruit in Grave's disease).
• Adrenal: Signs of Cushing's (moon face, buffalo hump, striae, central obesity, hypertension), Addison's (pigmentation, postural hypotension).
• Pituitary: Signs of acromegaly, gigantism, pan-hypopituitarism.

Summary: Sequence of a Complete Examination

1. Wash hands, introduce yourself, obtain consent
2. Position and exposure
3. General inspection (from end of bed)
4. Vital signs
5. Hands → Arms → Face/Head/Neck → Chest → Abdomen → Lower limbs → Back
6. Systemic examination of relevant system(s)
7. Neurological if indicated
8. Document findings clearly

• Bailey and Love's Short Practice of Surgery, 28th Edition
• Rheumatology, 2-Volume Set (Elsevier, 2022)
• Bradley and Daroff's Neurology in Clinical Practice

Wild Type Phenotype

Definition

• The term "wild type" comes from the idea of organisms found "in the wild" - i.e., in their natural state.
• It is commonly abbreviated as wt, WT, or symbolized by a + in genetic notation.
• The wild type allele is the allele that produces this normal phenotype.

"A phenotype is a description of a whole organism, and is a result of the expression of the organism's genotype in a particular environment."

• Kandel's Principles of Neural Science, 6th Edition

Genotype vs. Phenotype (Background)

Wild Type in Relation to Mutant Phenotypes

1. Recessive Mutant Phenotype

• The mutant phenotype is expressed only when both alleles are mutant (homozygous mutant, or compound heterozygote).
• A single wild type allele (+/mutant) is enough to maintain the normal (wild type) phenotype.
• This occurs because one functional copy of the gene produces enough protein for normal function.
• Example: Cystic fibrosis - one wild type CFTR allele is sufficient; disease appears only when both alleles are mutant.

2. Dominant Mutant Phenotype

• One mutant allele in combination with one wild type allele (+/mutant) is enough to produce the mutant phenotype.
• Two main mechanisms:
  • Haploinsufficiency: 50% of the gene product (from the single wild type allele) is not sufficient for a normal phenotype. Example: NF1 mutations.
  • Dominant negative effect: The mutant protein actively interferes with (antagonizes) the product of the wild type allele. Example: TP53 mutations in cancer.

"If a mutant phenotype results from a combination of one mutant and one wild-type allele, the phenotypic trait and mutant allele are said to be dominant."

• Kandel's Principles of Neural Science, 6th Edition

Key Properties of Wild Type

Wild Type in Medical Context

Cancer Genomics

• Wild type refers to the non-mutated form of a cancer-related gene.
• Example: KRAS wild type colorectal cancer responds to anti-EGFR therapy (cetuximab); KRAS-mutant cancers do not.
• BRAF wild type vs. BRAF V600E mutant melanoma - targeted therapy with vemurafenib only works in BRAF mutant tumors.

Pharmacogenomics

• Wild type alleles of drug-metabolizing enzymes (e.g., CYP2D6) define "normal" drug metabolism. Mutant alleles cause poor or ultra-rapid metabolism.

Mitochondrial Genetics

• Cells can have a mixture of wild type and mutant mitochondrial DNA - a state called heteroplasmy.
• If the proportion of mutant mtDNA exceeds a threshold, the wild type phenotype is lost and disease appears. If 100% wild type, this is called homoplasmy for wild type.

"...causes the disease expression, or 100% wild-type homoplasmy."

• Harrison's Principles of Internal Medicine, 22nd Edition

Recessive Inheritance

• A phenotype is recessive if it is expressed only in individuals who lack a wild type allele entirely (homozygous mutants or compound heterozygotes).
• A phenotype is dominant if it is expressed even when a wild type allele is present.

"A phenotype is recessive if it is expressed only in homozygotes or compound heterozygotes, all of whom lack a wild-type allele, and never in heterozygotes, who do have a wild-type allele."

• Thompson & Thompson Genetics and Genomics in Medicine, 9th Edition

Wild Type in Microbiology

• Wild type bacteria can grow on minimal media (prototrophic).
• Auxotrophic mutants require additional nutrients the wild type does not need.
• Complementation testing: A wild type gene frequently complements its mutant homologue, restoring the wild type phenotype. This is used in merodiploid analysis to study allele interactions.

"A wild-type gene frequently complements its mutant homologue, and selection for the wild-type phenotype can allow maintenance of merodiploids in the laboratory."

• Jawetz, Melnick & Adelberg's Medical Microbiology, 28th Edition

Summary Table

• Thompson & Thompson Genetics and Genomics in Medicine, 9th Edition
• Kandel's Principles of Neural Science, 6th Edition
• Harrison's Principles of Internal Medicine, 22nd Edition
• Jawetz, Melnick & Adelberg's Medical Microbiology, 28th Edition