Orthopedic Postgraduate Exam Review: Basic Sciences and Applied Sciences Study Guide

SECTION 1: BASIC AND APPLIED SCIENCES

CALCIUM METABOLISM

1. General Properties

   • Calcium is the most abundant cation in the human body.

   • Total amount of calcium in an adult ($60\,kg$) = $1.2\,kg$.

   • Distribution:

     • $99\%$ Skeleton: Consists of a $99\%$ non-exchangeable pool and a $1\%$ exchangeable pool with extracellular fluid (ECF).

     • $1\%$ Plasma ECF ($9-11\,mg/dL$): $53\%$ is unfiltrate (Ionized or Complexed); $47\%$ is protein-bound to albumin and globulin.

2. Daily Requirements

   • Adult: $1,000\,mg/day$

   • Pregnant: $1,200-1,500\,mg/day$

   • Lactating: $2,000\,mg/day$

   • Infants: $500\,mg/day$

3. Preparations and Sources

   • Common Preparations: Ca gluconate, Ca lactate, Ca carbonate.

   • Sources: Milk, green leafy vegetables, drinking water, fish, Fruits (Sitaphal), Dry fruits (Dates), Ragi, and egg yolk.

4. Calcium Absorption and Excretion

   • Absorption: Vitamin D mediated; $50\%$ absorption occurs in the duodenum and upper jejunum ($500\,mg$).

   • Excretion Paths:

     • Skin (Sweat): $30-150\,mg$

     • Stool: $650\,mg$ (Total dietary excretion minus endogenous loss of $150\,mg$ from digestive juices).

     • Urine: $200\,mg$ ($99\%$ reabsorbed in the kidney: $65\%$ from PCT, $10\%$ from distal nephron under PTH control).

5. Biological Functions

   • Primary constituent for bone formation and resorption.

   • Essential for blood coagulation and neuromuscular excitation.

   • Required for transmission of nerve impulses and cellular adhesiveness.

   • Maintenance and function of cell membranes.

   • Activation of specific enzymes and aid in nucleic acid/protein synthesis.

RICKETS

1. Definition

   • A metabolic bone disease characterized by a defect in the mineralization of osteoid matrix due to inadequate Calcium and Phosphorus, occurring prior to the closure of the physis.

2. Vitamin D Metabolism

   • Skin: UVB sunlight converts 7-Dehydrocholesterol to Vitamin $D_3$ (Cholecalciferol).

   • Liver: $25\text{-Hydroxylase}$ converts $D_3$ to $25(OH)D_3$.

   • Kidney: $1,25\text{-Hydroxylase}$ converts $25(OH)D_3$ to $1,25(OH)_2D_3$ (Calcitriol).

   • Action of Calcitriol: Increases Calcium and Phosphorus absorption and bone formation; provides negative feedback to PTH and its own renal secretion.

3. Etiological Classification

   • Vitamin D Disorders: Nutritional deficiency, Vitamin D-dependent types 1 and 2 (VDDR-1, VDDR-2), Congenital deficiency, malabsorption, and Chronic Renal Failure (CRF).

   • Renal Losses: Vitamin D-resistant rickets (familial hypophosphatemic), Fanconi syndrome, and Renal tubular acidosis.

   • Production of Phosphatonins: McCune-Albright syndrome, Neurofibromatosis, Tumor-induced.

   • Calcium Deficiency: Low intake or malabsorption.

   • Phosphate (PO$_4$) Deficiency: Premature infants, aluminum-containing antacids.

4. Pathophysiology

   • Nutritional: $\downarrow 1,25D_3 \rightarrow \downarrow Sr. Ca \rightarrow \uparrow PTH \rightarrow \text{Bone resorption}$. Leads to failure of calcification of cartilage/osteoid, joint swelling, and pressure cupping of metaphysis.

   • Vitamin D-Resistant (VDRR): Most common heritable form ($1-2$ years of age). Caused by renal tubule inability to absorb phosphate.

     • Types: X-LD (PHEX gene mutation), AD (FGF23 mutation), AR (DMP-1 or FGF23 gene mutation).

5. Clinical Features

   • General: Failure to thrive, listlessness, generalized muscle weakness, protuberant abdomen, and hypocalcemic tetany.

   • Head: Craniotabes, frontal bossing, and delayed dentition/fontanelle closure.

   • Spine: Kyphosis ("Rachitic Cat back"), Scoliosis, and increased lumbar lordosis.

   • Chest: Rachitic rosary, Harrison's sulcus, and Pectus carinatum.

   • Limbs: Bone pain, Coxa vara, Genu varum > Genu valgus, Windswept deformity, bowing of long bones, and widening of joints. "Double malleoli sign" due to enlarged ankle epiphysis.

6. Radiology

   • Cupping, fraying, and widening of the physis.

   • Generalized osteopenia (low bone density).

   • Looser's Zones: Sharply defined radiolucent transverse zones (pseudofractures) caused by pulsatile artery pressure against soft bone.

7. Treatment

   • Nutritional: STOSS therapy ($3,00,000-6,00,000\,IU$ Vitamin $D_3$ over $1-5$ days) or $60,000\,IU$ weekly, followed by $800\,IU/day$ and Calcium ($500\,mg/day$).

   • VDRR: Oral phosphorus.

   • VDDR-1: Calcitriol.

   • VDDR-2: High-dose Vitamin $D_3$.

   • Deformities: Hemiepiphysiodesis for skeletally immature or osteotomy for mature patients.

OSTEOMALACIA

1. Introduction

   • Adult metabolic bone disease with defective mineralization causing accumulation of unmineralized osteoid tissue. Bone catabolism and anabolism are normal.

2. Etiology

   • Vitamin D deficiency (pregnancy, anti-epileptics, poor nutrition, low SES).

   • Gastrointestinal disorders (post-gastrectomy, celiac disease).

   • Phosphate depletion (renal leak, chronic antacid use).

3. Clinical Features

   • Proximal muscular weakness, waddling gait (hip adductor weakness).

   • Pathological fractures (vertebral compression), Coxa vara, Protrusio acetabuli.

4. Radiograph and Labs

   • Generalized demineralization (loss of transverse trabeculae).

   • Cod-fish spine: Nucleus pulposus expands and indents vertebral end plates.

   • LOOSER ZONES (Pseudofractures): Bilateral symmetrical transverse lines of rarefaction (neck of femur, rib, ischium).

   • Labs: $\downarrow Sr.\,Ca, \downarrow Sr.\,P, \downarrow Vit.\,D_3, \uparrow ALP, \uparrow PTH$.

OSTEOPOROSIS

1. Overview

   • Reduction in bone density where resorption rate exceeds formation.

   • WHO Definition: Bone Mineral Density (BMD) $2.5$ Standard Deviations (SD) below the mean for young adults (T-score).

2. Pathogenesis

   • Bone mass increases until $25-30$ years; maintained until $45$; thereafter resorption exceeds formation (remodeling imbalance).

   • Accelerated loss in women after menopause.

3. Risk Factors

   • Non-modifiable: Advanced age, ethnicity, genetics (OI, Marfan's), family history of fragility fracture.

   • Modifiable: Low BMI (F < 20, M < 25), glucocorticoids, smoking, alcohol, $>4 cups of coffee/day, prolonged immobilization, space travel.\n\n4. **Classification (Riggs and Melton)**\n * **Primary:** Type 1 (Postmenopausal, High turnover, vertebral fractures) and Type 2 (Senile/Involutional, Low turnover, age $>75$, hip fractures).\n * **Secondary:** Hormonal, Nutritional, Drugs, Chronic liver/renal disease.\n\n5. **Diagnostics**\n * **Singh's Index:** Grading trabecular loss in the proximal femur (Grade 1=6; Grade 1 is the most severe loss).\n * **DEXA (Dual Energy X-ray Absorptiometry):** Gold standard. Reports reported in g/cm^2; utilizes Z-score (age-matched) and T-score (peak bone mass matched for fracture risk prediction).\n * **Bone Turnover Markers:** \n * Formation: Procollagen 1 carboxy terminal propeptide (PICP, PINP), osteocalcin.\n * Resorption: Plasma tartrate-resistant acid phosphatase (TRAP), urinary hydroxyproline, N-telopeptide.\n\n6. **Treatment**\n * **Calcium/Vit D:** Prophylactic (1,200-1,500\,mg/d Ca for postmenopausal women).\n * **Bisphosphonates:** First-line for prevention/treatment if T\text{-score} < -2.5.\n * **Calcitonin:** Relieves pain in acute vertebral fractures.\n * **Teriparatide:** Recombinant PTH; activates osteoblasts. Contraindicated in Paget's/Osteosarcoma risk.\n * **Denosumab:** Monoclonal against RANKL.\n * **Romosozumab:** Monoclonal Ig2 binding to sclerostin (activates Wnt pathway).\n\n# BISPHOSPHONATES (BP)\n\n1. **Mechanism of Action**\n * Accumulate in bones; ingested by osteoclasts. \n * **Nitrogen-containing (N-BP):** Inhibit farnesyl pyrophosphate synthase, preventing GTP formation required for osteoclast survival (Cytoskeletal alterations/death).\n * **Non-nitrogen containing:** Produce toxic ATP analogs leading to premature apoptosis.\n\n2. **Clinical Notes**\n * **Effects:** "Metabolic freeze" leads to increased bone strength initially, but bone becomes brittle with prolonged use.\n * **Classification:** Oral (Alendronate, Risedronate) vs IV (Zoledronic acid - once a year).\n * **Adverse Reactions:** Influenza-like illness, Esophageal ulceration, BRONJ (Bisphosphonate-related Osteonecrosis of the Jaw), and Atypical subtrochanteric fractures.\n\n# PARATHYROID DISORDERS\n\n1. **PTH Mechanism**\n * Stimulates bone resorption via osteoblasts (receptor activation of RANKL).\n * Secretion stimulated by low serum Calcium.\n\n2. **Categories**\n * **Primary:** Parathyroid adenoma (75\% asymptomatic). Classical signs: "Stones, groans, bones, and psychiatric moans."\n * **Secondary:** Chronic renal failure (MCC) or Malabsorption.\n * **Tertiary:** ESLD; fixed autonomous PTH production despite Ca levels.\n\n3. **Brown Tumor**\n * Reparative cellular process (not neoplastic) seen in hyperparathyroidism. \n * **Histology:** Multinucleated giant cells in Howship's lacunae; hemosiderin creates the brown color.\n\n# SCURVY\n\n1. **Etiology**\n * Nutritional disorder from severe Vitamin C deficiency. Bimodal age group: 5-10$months and$>60 years.\n * **Pathology:** Deficiency in chondroitin sulfate and collagen leads to impaired cohesive connective tissue property.\n\n2. **Radiology**\n * **White line of Frankel:** Broadened zone of provisional calcification.\n * **Trummerfeld zone:** Radiolucent "Scurvy line" of bone resorption.\n * **Wimberger ring sign:** Dense ring around epiphysis.\n * **Corner sign of Park:** Metaphyseal clefts.\n * **Pelkan spurs:** Metaphyseal fractures.\n\n# SKELETAL FLUOROSIS\n\n1. **Mechanism**\n * Fluoride replaces hydroxyl groups in calcium hydroxyapatite to form calcium fluorapatite.\n * Upper safe limit: 6\,mg/day. \n\n2. **Clinical Symptoms**\n * Prolonged symptom-free period (10-30 years) followed by radiculomyelopathy from spinal sclerosis/osteophytes.\n * Radiology: Ground-glass appearance of bone; marked calcification of ligaments (paraspinous, sacrospinous).\n\n# SKELETAL DEVELOPMENT\n\n1. **Ossification Types**\n * **Intramembranous:** Mesenchymal connective tissue forms membrane model (Skull, facial bones, distraction osteogenesis).\n * **Endochondral:** Cartilage model replaced by bone (Long bone formation, non-rigid fracture healing).\n\n2. **Joints**\n * Mesenchyme between bone ends condenses to form Interzonal mesenchyme (future joint sites).\n\n3. **Limb Buds**\n * Appear in 5^{\text{th}} week. AER (Apical Ectodermal Ridge) promotes growth.\n * 6^{\text{th}} week: Digit outlines. \n * 7^{\text{th}}$week: rotation (Upper limb rotates$90^\circ$laterally; Lower limb rotates$90^\circ medially).\n\n# BONE HEALING\n\n1. **Indirect Healing (Callus Formation)**\n * **Stage 1: Hematoma (Day 1).** Disrupted vessels, fibrin fibers stabilize.\n * **Stage 2: Inflammation (Days 1-5).** Cytokines (TNF\text{-}\alpha, IL\text{-}1,6) trigger vasodilation. MSC migration.\n * **Stage 3: Granulation Tissue (Days 5-14).** Fibrovascular pro-callus forms.\n * **Stage 4: Soft Callus (Weeks 2-4).** Fibrocartilage anchorage.\n * **Stage 5: Hard Callus (Weeks 4-16).** Woven bone transforms to lamellar through Enchondral ossification.\n * **Stage 6: Remodeling (Weeks 16 to years).** Osteoclasts form cutting cones; bone follows Wolff's Law (functional stress).\n\n2. **Direct Repair**\n * No callus. Requires rigid fixation (Contact healing < 200\mu$,$Gap healing 200-500\mu).\n\n# CARTILAGE\n\n1. **Articular Cartilage Zones**\n * **Superficial (Tangential):** Parallel collagen, flat chondrocytes.\n * **Transitional (Intermediate):** Random collagen, round chondrocytes.\n * **Deep (Basal):** Perpendicular collagen, linear arrangement.\n * **Calcified:** Separated by the tidemark; lacks supply, never heals if injury is superficial.\n\n2. **Outerbridge Classification of Defects**\n * Grade 0: Normal.\n * Grade 1: Softening/Swelling.\n * Grade 2: Superficial fissures.\n * Grade 3: Deep fissures ("crab meat").\n * Grade 4: Exposed subchondral bone.\n\n3. **Procedures**\n * **Microfracture:** 3-4\,mm$deep perforations in subchondral bone to access MSCs (lesions$<2-3\,cm^2).\n * **OATS/Mosaicplasty:** Cylinder bone plugs from low-weight bearing donor sites.\n * **ACI (Autologous Chondrocyte Implantation):** Two-stage cell-based therapy harvesting cells arthroscopically then re-implanting under periosteal flap.\n\n# GAIT ANALYSIS\n\n1. **Basics**\n * **Stance Phase (60\%):** Heel strike, Foot flat, Mid-stance, Heel off, Toe off.\n * **Swing Phase (40\%):** Acceleration, Mid-swing, Deceleration.\n * **Center of Gravity:** 5\,cm$in front of$S_2. \n\n2. **Pathological Gaits**\n * **Trendelenburg (Abductor Lurch):** Defective abductor mechanism (Gluteus medius/minimus). Sound side of pelvis drops during swing phase.\n * **Antalgic:** Pain in weight-bearing limb; short stance phase.\n * **Rocking Horse:** \text{Gluteus maximus} dysfunction.\n * **Scissoring:** Common in CP (Cerebral Palsy).\n * **Hand-to-knee:** Weak quadriceps; patient physically pushes thigh back to prevent buckling.\n\n# BLOOD AND TRANSFUSION\n\n1. **Red Blood Cells (PRBC):** 1 unit raises Hb by 1.2\,g/dL$. Storage at$2-6^\circ C.\n2. **PRP (Platelet Rich Plasma):** Count 4-5 times normal. Used for Lateral epicondylitis and Rotator cuff tears.\n3. **Cryoprecipitate:** Contains Fibrinogen and Factor VIII. Used for Hemophilia/Von Willebrand disease.\n\n# THROMBOPROPHYLAXIS\n\n1. **LMWH (Low Molecular Weight Heparin):** Enoxaparin 20\,mg$BD (low risk) or$40\,mg$BD (high risk). Inactivates factors$IIa, IXa, Xa.\n2. **Fat Embolism Triad:** Cardiopulmonary dysfunction (tachycardia, tachypnea), Neurologic dysfunction (confusion), and Cutaneous changes (petechial rash in neck/axilla).\n\n# COMPARTMENT SYNDROME\n\n1. **Vicious Circle (Eaton and Green):** \text{Arterial damage} \rightarrow \text{Ischemia} \rightarrow \text{Edema} \rightarrow \uparrow \text{Pressure} \rightarrow \text{Vascular compression}.\n2. **Thresholds:** Absolute pressure of 30\,mmHg$(Mubarak) or Delta Pressure ($\text{Diastolic BP} - \text{Intracompartmental Pressure} < 30).\n3. **Clinical Signs:** Pain out of proportion, pain with passive stretch, palpably tense, paresthesia, paralysis, pallor, pulselessness.\n4. **Tissue Survival:** Muscle (8\,hours$irreversible), Nerves ($8\,hours irreversible).\n5. **Fasciotomy:** Leg requires single (Matsen) or double (Mubarak) incisions separating 4 compartments. Forearm has 3 compartments (Volar, Dorsal, Mobile Wad).\n\n# SECTION 2: PEDIATRIC ORTHOPEDICS\n\n# PROXIMAL FEMORAL FOCAL DEFICIENCY (PFFD)\n\n1. **Classification (Aitken)**\n * **Type A:** Femoral head present; short femoral segment; subtrochanteric varus.\n * **Type B:** Femoral head present; Moderately dysplastic acetabulum; no osseous connection between head and shaft.\n * **Type C:** Femoral head absent/ossicle; Severe acetabular dysplasia; short tapered segment.\n * **Type D:** Femoral head absent; enlarged acetabulum; no relationship between femur parts.\n\n2. **Van Nes Rotationplasty:** Limb is rotated 180^\circ to allow the ankle to function as a knee joint for prosthetic fitting.\n\n# PERTHES DISEASE\n\n1. **Etiology:** Avascular necrosis of the femoral head epiphysis. Associated with ADHD, passive smoking, and the COL2A1 gene.\n2. **Waldenstrom Stages:** Initial (Sclerosis), Fragmentation (Fissures), Reconstitution (New bone at periphery), and Complete healing.\n3. **Herring (Lateral Pillar) Classification:** \n * Group A: No loss of height.\n * Group B: Loss <50\%.\n * Group C: Loss >50\%$$.

4. Head at Risk Signs: Gage's sign (V-shaped lucent defect), calcification lateral to epiphysis, and lateral subluxation.