🔄 Flowchart Migration Preview

flowchart TD Start["🔍 Interim Analysis
• Pre-planned data review• Conducted by DSMB• Occurs before completion"] Penalty["⚖️ Statistical Penalty
• Alpha-spending function• Preserves Type I error rate• Prevents 'p-hacking' bias"] Decision{"🛑 Stop for Efficacy/Futility?
• Efficacy: Overwhelming benefit• Futility: No hope of benefit"} Terminate["⚠️ Terminate Trial
• Ethical duty to report• Notify IRB and FDA• Early analysis of results"] Continue["🏃 Continue Trial
• Maintain study masking• Continue patient enrollment"] Adjustments["⚙️ Trial Adjustments
• Sample Size Re-estimation• Adaptive design elements• Corrects underpowered studies"] Start --> Penalty Start --> Decision Decision -- "Yes" --> Terminate Decision -- "No" --> Continue Continue --> Adjustments style Start fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Penalty fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Decision fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Terminate fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Continue fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Adjustments fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845

flowchart TD A["🌬️ Hypoxia
• Low partial pressure of O2• Trigger for adaptive response• Common in high altitude or anemia"] B["🧬 HIF-1alpha stabilization
• Reduced degradation by VHL protein• Accumulation of transcription factor• Binds to Hypoxia Response Elements"] C["Kidney Renal EPO gene transcription
• Peritubular interstitial cells• Increased Erythropoietin mRNA• Secretion into systemic circulation"] D["🦴 Bone marrow erythropoiesis
• Stimulates CFU-E progenitors• Inhibits erythroblast apoptosis• Increased reticulocyte production"] E["🩸 Increased Hematocrit and O2 capacity
• Higher red blood cell mass• Improved oxygen delivery to tissues• Restores homeostatic balance"] A --> B B --> C C --> D D --> E style A fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style B fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style C fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style D fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style E fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD A["🍄 Lanosterol
• Primary precursor in fungal sterol synthesis• Derived from squalene epoxide"] B["💊 Azoles Action
• Inhibits 14-alpha-demethylase enzyme• Cytochrome P450-dependent mechanism• Blocks conversion pathway to ergosterol"] C["🧬 Ergosterol
• Vital component of fungal cell membranes• Deficiency leads to membrane instability• Results in inhibited fungal cell growth"] A --> B B -- "X (Inhibited)" --- C style A fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style B fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style C fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["🩺 Thyroid Nodule + FNAC
• Discovery via imaging or palpation• Fine Needle Aspiration Cytology• Initial triage step"] Bethesda{"🔬 Bethesda Result
• Standardized cytopathology reporting• Guides clinical management"} Cat1["⚠️ I (Non-Diagnostic)
• Inadequate cellularity• Often due to cystic components"] Cat2["✅ II (Benign)
• Includes colloid and thyroiditis• Very low malignancy risk"] Cat34["🟡 III (AUS/FLUS) & IV (FN/SFN)
• Atypia or Follicular Neoplasm• Indeterminate risk categories"] Cat56["🚨 V (Suspicious) & VI (Malignant)
• High suspicion or definitive cancer• Papillary, medullary, or anaplastic"] Action1["🔄 Repeat FNAC
• Perform second aspiration• Consider ultrasound guidance"] Action2["📅 Follow-up USG 12-24 mo
• Serial ultrasound monitoring• Check for size increase"] Action34["🧬 Testing & Lobectomy
• Molecular Marker testing• Diagnostic surgical lobectomy"] Action56["🔪 Surgery
• Therapeutic thyroidectomy• Central node dissection possible"] Start --> Bethesda Bethesda --> Cat1 Bethesda --> Cat2 Bethesda --> Cat34 Bethesda --> Cat56 Cat1 --> Action1 Cat2 --> Action2 Cat34 --> Action34 Cat56 --> Action56 style Start fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Bethesda fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Cat1 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Cat2 fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Cat34 fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Cat56 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Action1 fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Action2 fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style Action34 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Action56 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD START["💊 Terbinafine Action
• Allylamine antifungal medication• Primary use for dermatophytoses• Highly lipophilic and keratinophilic"] INHIBIT["🚫 INHIBITION
• Blocks ergosterol biosynthesis• Targets fungal enzyme early step• Leads to toxic squalene buildup"] SUBST_SQ["🧪 Squalene
• Primary precursor molecule• Accumulation is fungicidal• High levels disrupt membranes"] ENZYME_B["🧬 B (Squalene Epoxidase)
• Rate-limiting enzyme in pathway• Converts squalene to lanosterol• Inhibited by terbinafine"] SUBST_LAN["⚗️ Lanosterol
• Intermediate sterol precursor• Product of squalene epoxidase• Substrate for 14-alpha demethylase"] OUT_ERG["🍄 Ergosterol
• Essential fungal membrane sterol• Maintains structural integrity• Target of multiple antifungal classes"] START --- INHIBIT INHIBIT -.-> ENZYME_B SUBST_SQ --> ENZYME_B ENZYME_B --> SUBST_LAN SUBST_LAN --> OUT_ERG style START fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style INHIBIT fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style ENZYME_B fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style SUBST_SQ fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style SUBST_LAN fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style OUT_ERG fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD DRUG_ACTION["💊 ANTIFUNGAL DRUGS
• Target ergosterol synthesis• Disrupt cell membrane integrity"] TERB["🍄 Terbinafine
• Inhibits squalene epoxidase• Causes squalene accumulation• Used for dermatophytoses"] SQ["🧪 Squalene
• Primary precursor molecule• Toxic at high concentrations"] LAN["🧪 Lanosterol
• Sterol intermediate• Product of epoxidase action"] AZO["💊 Azoles
• Inhibits 14-alpha-demethylase• Blocks Lanosterol conversion• Broad spectrum activity"] ERG["🧬 Ergosterol
• Essential fungal membrane component• Maintains membrane fluidity"] NYS["💊 Nystatin Polyenes
• Binds directly to ergosterol• Creates membrane pores• Amphotericin B is same class"] MEM["🛡️ Cell Membrane
• Critical for cell survival• Leakage leads to cell death"] DRUG_ACTION --> TERB DRUG_ACTION --> AZO DRUG_ACTION --> NYS TERB -- "X Inhibits" --> SQ SQ -- "Squalene Epoxidase" --> LAN AZO -- "X Inhibits 14-alpha-demethylase" --> ERG LAN -- "Conversion" --> ERG ERG -- "Forms" --> MEM NYS -- "X Disrupts pores" --> MEM style DRUG_ACTION fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style TERB fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style AZO fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style NYS fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style SQ fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style LAN fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style ERG fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style MEM fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD START["🩸 Hyperglycemia
• Sustained high glucose levels• Primary trigger for complications• Leads to metabolic shift"] ABERRANT["⚙️ Metabolic Changes
• Mitochondrial dysfunction• Cellular nerve damage• Impaired myelin sheath"] OXIDATIVE["🧪 Oxidative Stress
• Excessive oxidation• Uncoupled NO levels rise• Increased ROS production"] NEURO["🧠 Diabetic Neuropathy
• Sensory: Loss of sensation• Motor: Muscular atrophy• Autonomic: Reduced sweating"] ANGIO["⚠️ Angiopathy
• Microvascular dysfunction• Macrovascular dysfunction• Leads to tissue ischemia"] IMMUNE["🛡️ Immune Dysfunction
• Neutrophil/Macrophage defect• Chronic inflammation• Fibroblast dysfunction"] ISCHEMIA["📉 Tissue Ischemia
• A/V shunt opening• Atherosclerosis• Gangrene risk"] HEALING["⏳ Delayed Healing
• Decreased angiogenesis• Abnormal matrix proteinase• Skin breakdown and infection"] ULCER["🦶 Diabetic Foot Ulcer
• Multifactorial end result• High risk of infection• Potential for amputation"] START --> ABERRANT START --> OXIDATIVE ABERRANT --> NEURO ABERRANT --> ANGIO OXIDATIVE --> IMMUNE NEURO --> ULCER ANGIO --> ISCHEMIA IMMUNE --> HEALING ISCHEMIA --> ULCER HEALING --> ULCER style START fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style ABERRANT fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style OXIDATIVE fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style NEURO fill:#FCE4EC, stroke:#E91E63, stroke-width:2px, color:#4A0033 style ANGIO fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style IMMUNE fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style ISCHEMIA fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style HEALING fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style ULCER fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["🚨 Stimulus
• Increased Plasma Osmolality• Decreased Blood Volume• Detected by osmoreceptors"] Hypo["🧠 Hypothalamus Senses Change
• Supraoptic nuclei activation• Paraventricular nuclei activation• Thirst center stimulation"] Pit["💧 Posterior Pituitary Releases ADH
• Arginine Vasopressin (AVP)• Neurohypophysis secretion• Enters systemic circulation"] ADHact["🧪 ADH acts on Collecting Duct
• Binds to V2 receptors• G-protein cAMP pathway• Principal cells target"] AQP["🧬 Increased Aquaporin-2 (AQP2) Insertion
• Vesicle fusion with membrane• Apical membrane expression• Increased water permeability"] Water["🌊 Increased Water Reabsorption
• Passive flow along gradient• Medullary interstitium pull• Free water conservation"] Outcome["✅ Concentrated Urine & Low Osmolality
• Decreased Plasma Osmolality• High Urine Specific Gravity• Homeostasis restored"] Start --> Hypo Hypo --> Pit Pit --> ADHact ADHact --> AQP AQP --> Water Water --> Outcome style Start fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Hypo fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Pit fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style ADHact fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style AQP fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Water fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style Outcome fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD PYR["🧪 Pyruvate
• Derived from glycolysis• Cytoplasmic to matrix transport• 3-carbon carboxylic acid"] ACOA["⚡ Acetyl-CoA
• 2-carbon active fragment• High energy thioester bond• Key metabolic crossover point"] KREBS{"🔄 Krebs Cycle
• Occurs in mitochondrial matrix• Citric Acid or TCA cycle• Major source of reduced cofactors"} NADH["🔋 3 NADH
• Enters ETC Complex One• Yields approx 2.5 ATP each• Reduced electron carrier"] FADH["🔋 1 FADH2
• Enters ETC Complex Two• Yields approx 1.5 ATP each• Bound to succinate dehydrogenase"] GTP["💎 1 GTP
• Produced by substrate level phosphorylation• Energetically equivalent to ATP• Succinyl-CoA to Succinate step"] CO2["☁️ 2 CO2
• Oxidative decarboxylation waste• Diffuses out of mitochondria• Final carbon oxidation product"] PYR -- "PDC
(Pyruvate Dehydrogenase Complex)" --> ACOA ACOA --> KREBS KREBS --> NADH KREBS --> FADH KREBS --> GTP KREBS --> CO2 style PYR fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style ACOA fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style KREBS fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style NADH fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style FADH fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style GTP fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style CO2 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD Plan["📝 Plan Stage
• Define clear objectives• Identify target audience• Craft core messaging"] Create["🎨 Create Stage
• Credible medical evidence• Engaging narrative style• High-yield visual content"] Share["📲 Share Stage
• Select optimal platforms• Schedule peak timing• Relevant medical hashtags"] Engage["💬 Engage Stage
• Foster clinical dialogue• Interactive Q and A• User-Generated Content"] Monitor["📊 Monitor Stage
• Track reach analytics• Review user feedback• Assess audience sentiment"] Adapt["🔄 Adapt Stage
• Refine future strategy• Improve educational ROI• Update based on data"] Plan --> Create Create --> Share Share --> Engage Engage --> Monitor Monitor --> Adapt style Plan fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Create fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Share fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Engage fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Monitor fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Adapt fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["⚠️ ADR Occurs
• Adverse Drug Reaction• Noxious/unintended response• Occurs at normal doses"] Detect["🔍 Detection
• Clinical identification• Patient monitoring• Lab signal recognition"] Report["📝 Reporting (PvPI)
• Pharmacovigilance Program of India• Spontaneous reporting• Documentation of event"] Assess["⚖️ Assessment
• Causality analysis• Naranjo algorithm use• Severity categorization"] Understand["🧠 Understanding
• Mechanism of action• Risk factor analysis• Signal strengthening"] Prevent["🛡️ Prevention
• Risk mitigation strategies• Drug label updates• Clinical guidelines mod"] Start --> Detect Detect --> Report Report --> Assess Assess --> Understand Understand --> Prevent style Start fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Detect fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Report fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Assess fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Understand fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Prevent fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD Start["💊 Drug Administration
• Pharmacological agent input• Potential substrate for P-gp"] Approach["🔬 Drug Approaches Cell
• Presence in extracellular fluid• Passive or active transport entry"] Interact["🛡️ Interacts with P-gp
• Binding at plasma membrane• P-glycoprotein efflux pump"] Efflux["⚡ Drug Effluxed Out
• ATP-dependent active transport• Move against concentration gradient"] LowerConcentration["📉 Low Intracellular Drug
• Reduced cytoplasmic levels• Decreased therapeutic effect"] Outcomes["⚖️ Clinical Consequences
• Decreased Absorption• Decreased BBB Distribution• Increased Elimination"] Start --> Approach Approach --> Interact Interact -- "Requires ATP" --> Efflux Efflux --> LowerConcentration LowerConcentration --> Outcomes style Start fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style Approach fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style Interact fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style Efflux fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style LowerConcentration fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style Outcomes fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD START["🚨 Chest Pain / ACS Symptoms
• Pressure, squeezing, or fullness• Pain radiates to arms, neck, jaw• Associated diaphoresis or SOB"] ECG_DIAG["⚡ 12-Lead ECG
• Perform within 10 mins of arrival• Compare to prior ECG if available• Evaluate all anatomical leads"] ST_DECISION{"❓ ST-Segment Elevation?
• Measure at the J-point• Look for reciprocal changes"} STEMI_GO["🚑 STEMI: Activate Cath Lab
• Reperfusion is primary goal• Door-to-Balloon in (90 min)• Door-to-Needle in (30 min)"] NSTEMI_CHECK["🧪 NSTEMI / Unstable Angina
• Check High Sensitivity Troponins• Serial testing for trending• Risk stratify (TIMI or GRACE)"] START --> ECG_DIAG ECG_DIAG --> ST_DECISION ST_DECISION -- Yes --> STEMI_GO ST_DECISION -- No --> NSTEMI_CHECK style START fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style ECG_DIAG fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style ST_DECISION fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style STEMI_GO fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style NSTEMI_CHECK fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00

flowchart TD Start["🔍 ECG PR Assessment
• Measure from P start to QRS start• Normal range: 120-200ms"] CheckLongPR{"⏱️ Is PR > 0.20s?
• Greater than 5 small boxes• Indicates AV delay"} Normal["✅ Normal Conduction
• PR interval <= 0.20s• 1:1 P-to-QRS ratio"] CheckDropped{"📉 Is there a dropped QRS?
• Look for 'lonely' P waves• Check for non-conducted beats"} FirstDegree["🟦 1st Degree AV Block
• Constant PR > 0.20s• Every P wave followed by QRS• Usually benign/asymptomatic"] CheckProgressive{"📈 Is PR interval progressive?
• Compare successive PR intervals• Look for pattern of lengthening"} Mobitz1["🟪 2nd Degree Mobitz I
• Wenckebach phenomenon• PR lengthens until beat drops• Often nodal level block"] Mobitz2["⚠️ 2nd Degree Mobitz II
• Constant PR interval• Unexpected dropped QRS• High risk: May progress to 3rd deg"] ThirdDegree["🚨 3rd Degree (Complete)
• Total AV dissociation• No relationship P and QRS• Requires urgent evaluation"] Start --> CheckLongPR CheckLongPR -- "No" --> Normal CheckLongPR -- "Yes" --> CheckDropped CheckDropped -- "No" --> FirstDegree CheckDropped -- "Yes" --> CheckProgressive CheckProgressive -- "Yes" --> Mobitz1 CheckProgressive -- "No" --> Mobitz2 Mobitz2 --> ThirdDegree style Start fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style CheckLongPR fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Normal fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style CheckDropped fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style FirstDegree fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style CheckProgressive fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Mobitz1 fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Mobitz2 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style ThirdDegree fill:#FFEBEE, stroke:#F44336, stroke-width:4px, color:#5D0000

flowchart TD StartNode["👤 High-Risk Patient
• Immunocompromised state• Potential fungal risk"] DefectDecistion{"🔍 Immune Defect?
• Identify primary pathology• Categorize risk profile"} Neutropenia["🩸 Neutropenia (AML/MDS)
• Absolute Neutrophil Count low• High risk for invasive infection"] YeastCov["💊 Yeast Coverage
• Primary Rx: Fluconazole• Targets Candida species"] MoldCov["🍄 Yeast and Mold Coverage
• Primary Rx: Posaconazole• Targets Aspergillus and Mucor"] HSCT["🦴 Allogeneic HSCT
• Stem cell transplant recipient• Graft vs Host Disease risk"] Posaconazole["🛡️ Posaconazole
• Broad spectrum triazole• Prevents invasive aspergillosis"] HIV["🎗️ HIV/AIDS
• CD4 count monitoring• Opportunistic infection risk"] PJP["🫁 PJP Prophylaxis
• Rx: TMP-SMX (Bactrim)• Criteria: CD4 less than 200• Also covers some fungi"] Fluconazole["👄 Add Fluconazole
• Criteria: CD4 less than 100• Prevention: Esophageal Candidiasis"] Itraconazole["🌎 Add Itraconazole
• Criteria: CD4 less than 150• Prevention: Histoplasmosis• For Endemic Areas"] SOT["🫀 Solid Organ Transplant
• Heart, Lung, Liver, Kidney• Varies by organ and risk"] SOTOutcome["⚖️ Individualized Guard
• Fluconazole or Echinocandin• Depends on surgical risk"] StartNode --> DefectDecistion DefectDecistion --> Neutropenia DefectDecistion --> HSCT DefectDecistion --> HIV DefectDecistion --> SOT Neutropenia --> YeastCov Neutropenia --> MoldCov HSCT --> Posaconazole HIV -- "CD4 < 200" --> PJP HIV -- "CD4 < 100" --> Fluconazole HIV -- "Endemic & CD4 < 150" --> Itraconazole SOT --> SOTOutcome style StartNode fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style DefectDecistion fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Neutropenia fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style YeastCov fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style MoldCov fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style HSCT fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Posaconazole fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style HIV fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style PJP fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Fluconazole fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Itraconazole fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style SOT fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SOTOutcome fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00

flowchart TD ROOT["🧫 Antifungal Resistance Mechanisms
• Overview of common pathways• Genomic and efflux adaptations"] %% Azoles Branch AZ["💊 Azoles
• Inhibit Lanosterol 14-alpha-demethylase• Examples: Fluconazole, Voriconazole"] AZ_T["🧬 Target Mod: ERG11 mutation
• Altered enzyme binding site• Most common mechanism in Candida"] AZ_E["📤 Increased Efflux Pumps
• CDR and MDR gene over-expression• Rapid drug removal from cell"] %% Echinocandins Branch EC["🧪 Echinocandins
• Inhibit Beta-1,3-D-glucan synthase• Examples: Caspofungin, Micafungin"] EC_T["🧬 Target Mod: FKS1 mutation
• Hot-spot mutations in FKS subunits• Reduced drug sensitivity"] %% Polyenes Branch PY["🧴 Polyenes
• Bind directly to Ergosterol• Example: Amphotericin B"] PY_T["🧬 Target Mod: ERG3 mutation
• Decreased membrane Ergosterol• Results in 'leaky' membranes"] %% Flucytosine Branch FL["💊 Flucytosine
• Antimetabolite (5-FU precursor)• DNA/RNA synthesis inhibition"] FL_M["📉 Decreased Uptake / Metabolism
• Loss of Cytosine Permease• Decreased Deaminase activity"] %% Connections ROOT --> AZ ROOT --> EC ROOT --> PY ROOT --> FL AZ --> AZ_T AZ --> AZ_E EC --> EC_T PY --> PY_T FL --> FL_M %% Styling style ROOT fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style AZ fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style EC fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style PY fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style FL fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style AZ_T fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style AZ_E fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style EC_T fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style PY_T fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style FL_M fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD Start["🧫 Suspected Candidemia
• Obtain blood cultures promptly• Rule out endocarditis/ophthalmitis"] Stability{"⚖️ Hemodynamic Stability?
• Assess BP and lactate levels• Evaluate for septic shock signs"} Unstable["⚠️ Echinocandin Therapy
• Caspofungin or Micafungin• Preferred for critically ill patients"] Stable["💊 Fluconazole OR Echinocandin
• Fluconazole if no recent azoles• Consider local resistance patterns"] Susceptibility{"🔬 Isolate Susceptible?
• Review microbiology sensitivities• Confirm species (e.g., C. albicans)"} StepDown["📉 Step-down to Fluconazole
• Transition once clinically stable• Ensures cost-effective oral therapy"] ContinueECH["🛡️ Continue Echinocandin
• Use for C. glabrata or C. krusei• For azole-resistant strains"] Complete["✅ 14-day Course
• Duration starts post-clearance• Negative repeat cultures required"] Start --> Stability Stability -- "Unstable / Critically Ill" --> Unstable Stability -- "Stable" --> Stable Unstable --> Susceptibility Stable --> Susceptibility Susceptibility -- "Yes" --> StepDown Susceptibility -- "No" --> ContinueECH StepDown --> Complete ContinueECH --> Complete style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Stability fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Unstable fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Stable fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Susceptibility fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style StepDown fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style ContinueECH fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Complete fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD START["#129482; Suspected Infection
• Clinical signs of sepsis• Localized symptoms (cough, UTI)• Fever or elevated WBC count"] COLLECT["#129656; Cultures Drawn?
• Blood, urine, or sputum• Obtain BEFORE first dose• Minimize contamination risk"] GET_CULT["#10071; GET CULTURES FIRST!
• Antibiotics mask results• Crucial for ID accuracy• Draw aerobic/anaerobic bottles"] EMPIRIC["#128138; Start Broad-Spectrum Empiric Therapy
• Cover most likely pathogens• Follow local antibiograms• Adjust for risk of MDRO"] RESULTS["#128196; Culture and Sensitivity Results Available
• Final Gram stain/ID confirmed• Susceptibility profile (MICs)• Done within 48 to 72 hours"] DE_ESC["#9989; De-escalate to Narrow-Spectrum Definitive Therapy
• Targeted pathogen treatment• Reduce toxicity and cost• Prevent antibiotic resistance"] START --> COLLECT COLLECT -- NO --> GET_CULT GET_CULT --> EMPIRIC COLLECT -- YES --> EMPIRIC EMPIRIC --> RESULTS RESULTS --> DE_ESC style START fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style COLLECT fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style GET_CULT fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style EMPIRIC fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style RESULTS fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style DE_ESC fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["🚀 Start
• Initialize telematic analysis• Prepare processing environment"] SelectVar["📥 Select Telematic Variable
• Choose deceleration/acceleration• Identify primary driving metrics"] Preprocess["🧹 Preprocess Data
• Handle missing data points• Normalize and scale inputs"] NSPCA1["📉 Apply NSPCA: Variable 1
• Process deceleration patterns• Dimension reduction step 1"] Check1{"⚖️ Var. Exp. > Thresh?
• Variance explained check• Validation of components"} SelectPC1["📋 Select PCs: Variable 1
• Filter principal components• Retain key features"] NSPCA2["📊 Apply NSPCA: Variable 2
• Process right turn speed• Dimension reduction step 2"] Check2{"⚖️ Var. Exp. > Thresh?
• Variance explained check• Quality assurance step"} SelectPC2["📋 Select PCs: Variable 2
• Refine component selection• Finalize variable reduction"] FeatureSet["🏗️ Form Input Feature Set
• Combine n reduced variables• Construct model matrix"] PricingModel["💰 Build Pricing Model
• Regression or GLM approach• Actuarial risk calculation"] RiskMetrics["📈 Output Risk Metrics
• Calculate claim frequency• Predict loss ratios"] Stop["🛑 Stop
• Review final risk profile• Deployment of pricing strategy"] Start --> SelectVar SelectVar --> Preprocess Preprocess --> NSPCA1 NSPCA1 --> Check1 Check1 -- "Yes" --> NSPCA2 Check1 -- "No" --> SelectPC1 SelectPC1 --> NSPCA2 NSPCA2 --> Check2 Check2 -- "Yes" --> FeatureSet Check2 -- "No" --> SelectPC2 SelectPC2 --> FeatureSet FeatureSet --> PricingModel PricingModel --> RiskMetrics RiskMetrics --> Stop style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style SelectVar fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Preprocess fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style NSPCA1 fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Check1 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style SelectPC1 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style NSPCA2 fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Check2 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style SelectPC2 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style FeatureSet fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style PricingModel fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style RiskMetrics fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style Stop fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD Start["💊 Antibiotic Therapy Process
• Integrate clinical data• Review patient history• Microbiological findings"] Decision1{"⚖️ Selection Type
• Single vs. Combined• Assess severity of infection"} SortSingle["📊 Sort by Efficiency
• Rank by pathogen sensitivity• Pharmacokinetic profile"] SelectSingle["✅ Select Single Therapy
• Target specific organism• Narrowest spectrum possible"] OutcomeSingle["💊 Final Single Agent
• Begin monotherapy• Monitor clinical response"] DefineCriteria["🎯 Define Criteria
• Spectrum coverage and activity• Toxicity and protection risk"] DefineConstraints["⛓️ Define Constraints
• Num. protected sites• Min increment / Max overlap"] CreateCombos["⚙️ Create Combinations
• Synergistic interactions• Complementary mechanisms"] SortCombos["📈 Clinical Sort
• Align with patient condition• Comorbidity adjustments"] Decision2{"❓ Any Suitable?
• Review efficacy vs risk"} SelectCombo["🤝 Select Combination
• Final multi-drug regimen• Optimize dosing schedule"] OutcomeCombo["💊+💊 Final Combination
• Multidrug initiation• Watch for drug interactions"] %% Connections Start --> Decision1 Decision1 -- "[Single]" --> SortSingle SortSingle --> SelectSingle SelectSingle --> OutcomeSingle Decision1 -- "[Combined]" --> DefineCriteria DefineCriteria --> DefineConstraints DefineConstraints --> CreateCombos CreateCombos --> SortCombos SortCombos --> Decision2 Decision2 -- "[No]" --> DefineCriteria Decision2 -- "[Yes]" --> SelectCombo SelectCombo --> OutcomeCombo %% Styling style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Decision1 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style SortSingle fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SelectSingle fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style OutcomeSingle fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style DefineCriteria fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style DefineConstraints fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style CreateCombos fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style SortCombos fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Decision2 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style SelectCombo fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style OutcomeCombo fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD subgraph HUMAN_HOST ["👤 Human Host Stage"] START["🦟 Sporozoites Injected
• Inoculated by Anopheles mosquito• Travel via bloodstream to liver"] LIVER{"🌳 Liver Stage
• Exo-erythrocytic cycle• Schizonts mature in hepatocytes"} HYPNO["💤 Hypnozoites
• Dormant liver phase• Specific to P. vivax and P. ovale• Cause of clinical relapse"] FEVER["🔥 Erythrocytic Stage
• RBC rupture causes fever spikes• Merozoite release into blood"] GAMETES["🧬 Gametocytes
• Male and female sexual forms• Circulating in peripheral blood"] end subgraph MOSQUITO_HOST ["🦟 Mosquito Host Stage"] INGEST["🍽️ Gametocyte Ingestion
• Mosquito takes blood meal• Sexual cycle begins in midgut"] SEXUAL["❤️ Sexual Reproduction
• Ookinetes and Oocysts form• Sporogeny occurs in mosquito"] SALIVA["💧 Salivary Glands
• Sporozoites migrate to glands• Ready for next transmission"] end %% Human Cycle Connections START --> LIVER LIVER -->|Clinical disease| FEVER LIVER -.->|P. vivax or ovale| HYPNO FEVER -->|Cycles| FEVER FEVER --> GAMETES %% Transmission Connections GAMETES --> INGEST INGEST --> SEXUAL SEXUAL --> SALIVA SALIVA --> START %% Styling style START fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style LIVER fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style HYPNO fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style FEVER fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style GAMETES fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style INGEST fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style SEXUAL fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SALIVA fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["🏥 Hospital Setting
• Allocation of stewardship paths• Focus on antimicrobial resistance"] Wards["🏢 General Wards
• Standard inpatient care areas• Non-emergent antibiotic starts"] ICUs["🚑 Intensive Care Units (ICUs)
• High acuity patient care• Urgent empiric therapy needs"] Path1["📝 Path 1: Pre-Prescription
• Authorization required first• Needs ID specialist approval"] Path2["🔍 Path 2: Post-Prescription
• Review/feedback/audit model• 3-day empiric limit applied"] Computer1["💻 Computer Prescription (*)
• Order entry after validation• Linked to ID authorization"] IDContact["📞 Telephone ID Contact
• Direct specialist consultation• Verbal or electronic approval"] Release1["💊 Pharmacist Release (P1)
• Final clinical verification• Medication safety check"] Computer2["💻 Computer Prescription (#)
• Immediate ICU order entry• Empiric therapy initiation"] Release2["💊 Pharmacist Release (P2)
• Expedited clinical approval• Rapid antibiotic dispensing"] Audit["📋 Post-Prescription Audit
• ID specialist review of therapy• Escalation/De-escalation focus"] Start --> Wards Start --> ICUs Wards --> Path1 ICUs --> Path1 ICUs --> Path2 Path1 --> Computer1 Computer1 --> IDContact IDContact --> Release1 Path2 --> Computer2 Computer2 --> Release2 Release2 --> Audit Audit -- "If necessary" --> Path1 style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Wards fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style ICUs fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Path1 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Path2 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Computer1 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Computer2 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style IDContact fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Release1 fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style Release2 fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style Audit fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00

flowchart TD START["💊 Drug Concentration Profile
• Pharmacokinetic parameters• Time-dependent drug levels• Microbial killing efficacy"] CMAX["⚡ Cmax (Peak)
• Maximum peak concentration• Concentration-dependent killing• Example: Aminoglycosides"] AUC["📊 AUC (Area Under Curve)
• Total drug exposure (24h)• Integrated concentration-time• Example: Fluoroquinolones"] TIME["⏳ Time > MIC
• Duration over threshold• Time-dependent efficacy• Example: Beta-lactams"] MIC["🧫 MIC (Target)
• Minimum Inhibitory Conc• Standard for susceptibility• Inhibits visible growth"] START --> CMAX START --> AUC START --> TIME CMAX -- Peak Level --> MIC AUC -- Total Exposure --> MIC TIME -- Duration --> MIC style START fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style CMAX fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style AUC fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style TIME fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style MIC fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000

flowchart TD START["💊 Empiric Broad-Spectrum Antibiotic Started
• Target likely pathogens before culture• Risk of antibiotic resistance• Essential for severe sepsis/infection"] DECIDE{"🔍 Culture and Sensitivity Results Available?
• Check blood, urine, or tissue sites• MIC values for drug selection"} YES["🎯 De-escalate to Narrowest Effective Agent
• Switch to pathogen-specific drug• Reduces collateral damage to flora• Cost-effective treatment step"] NO["⚖️ Re-evaluate Diagnosis at 48-72h
• Monitor clinical response (SIRS)• Consider non-infectious causes• Repeat imaging or biopsy if needed"] END["✅ Complete Optimized Treatment Course
• Ensure compliance with duration• Switch to oral if clinically stable• Document end-of-therapy outcomes"] START --> DECIDE DECIDE -- Yes --> YES DECIDE -- No --> NO YES --> END NO --> END style START fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style DECIDE fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style YES fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style NO fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style END fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD Start["🔍 Patient Assessment
• Assess for renal impairment risk• Check age, weight, and comorbidities• Identify nephrotoxic drug intake"] Calc["🧮 Calculate CrCl
• Use Cockcroft-Gault Equation• Use actual vs ideal body weight• Serum Creatinine (SCr) required"] Decision1{"⚖️ CrCl > 50-60 mL/min?
• Threshold for drug adjustment• Normal vs impaired clearance"} Standard["✅ Standard Dosing
• Administer full clinical dose• Follow standard interval• No renal adjustment needed"] Adjust{"⚠️ Adjust Dose or Interval
• Reduce dose (maintain peaks)• Lengthen interval (reduce troughs)• Consult drug-specific nomograms"} Monitor["📊 Monitor Status
• Therapeutic Drug Monitoring (TDM)• Serial SCr and output checks• Watch for signs of toxicity"] Start --> Calc Calc --> Decision1 Decision1 -- Yes --> Standard Decision1 -- No --> Adjust Adjust --> Monitor style Start fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Calc fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Decision1 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Standard fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Adjust fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Monitor fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845

flowchart TD HF["❤️ Heart Failure
• Clinical syndrome of reduced CO• Elevated intracardiac pressures• Multiple etiologies (HTN/CAD)"] DT["🛠️ Dysfunction Type
• Classified by LVEF percentage• Mechanisms of cardiac output failure"] AS["🫀 Affected Side
• Based on chambers involved• Dictates primary venous congestion"] SYST["⚡ Systolic (Decreased EF)
• EF typically <= 40%• Reduced ventricular contractility• Often includes LV dilation"] DIAST["🔄 Diastolic (Impaired Filling)
• Normal or preserved EF• Stiff, non-compliant ventricle• High end-diastolic pressures"] LHF["🫁 Left HF (Pulmonary Congestion)
• Dyspnea, orthopnea, PND• Pulmonary rales and edema• S3 and S4 heart sounds"] RHF["🌊 Right HF (Systemic Congestion)
• Peripheral pitting edema• JVD and Hepatosplenomegaly• Most common cause: Left HF"] HF --> DT HF --> AS DT --> SYST DT --> DIAST AS --> LHF AS --> RHF style HF fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style DT fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style AS fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style SYST fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style DIAST fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style LHF fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style RHF fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD Start["🔍 Test Interpretation Strategy
• Diagnostic reasoning framework• Understanding SnNout vs SpIn"] %% Sensitivity Branch SensTest["🧪 High Sensitivity Test
• Ability to detect disease• Low False Negative rate• Screening tool utility"] SensResult["❌ Negative Result
• Patient lacks condition• High confidence in absence"] RuleOut["✅ Rule Out Disease - SNOUT
• SeNsitve test, Negative result• Effectively rules OUT disease"] %% Specificity Branch SpecTest["🔬 High Specificity Test
• Ability to identify health• Low False Positive rate• Confirmatory tool utility"] SpecResult["➕ Positive Result
• Disease likely present• High confidence in presence"] RuleIn["🚩 Rule In Disease - SPIN
• SPecific test, Positive result• Effectively rules IN disease"] %% Connections Start --> SensTest Start --> SpecTest SensTest --> SensResult SensResult --> RuleOut SpecTest --> SpecResult SpecResult --> RuleIn %% Styling style Start fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style SensTest fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style SensResult fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style RuleOut fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style SpecTest fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style SpecResult fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style RuleIn fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000

flowchart TD START["🔬 CL Diagnosis Confirmed
• Cutaneous Leishmaniasis• Confirmed by smear or PCR• Assess clinical presentation"] ASSESS{"⚖️ Assess Severity & Species
• Determine OWCL vs NWCL• Evaluate lesion number/size• Check for mucosal risk"} LOCAL_PATH["🏠 OWCL: Simple/Few Lesions
• Old World Cutaneous Leish• Minimal risk of dissemination"] SYSTEMIC_PATH["🏥 NWCL or Complex OWCL
• New World (risk of mucosal)• Multiple or resistant lesions"] LOCAL_OPT["💉 Local Therapy Options
• Targeted lesion treatment• Minimizes systemic toxicity"] SYSTEMIC_OPT["💊 Systemic Therapy
• Oral or parenteral route• Required for severe disease"] L1["📍 Intralesional SSG
• Sodium Stibogluconate• Direct injection into lesion"] L2["❄️ Cryo / Thermotherapy
• Physical destruction• Heat or cold application"] L3["🧴 Topical Paromomycin
• Aminoglycoside ointment• Simple OWCL lesions"] L4["⏱️ Observation
• Self-healing OWCL• Watchful waiting approach"] S1["🧪 Pentavalent Antimonials
• SSG 20 mg/kg/d IV or IM• Duration: 20-28 days"] S2["🫀 Amphotericin B (IV)
• Reserved for resistant cases• Liposomal form preferred"] S3["💊 Miltefosine (Oral)
• Dose: 2.5 mg/kg/d x 28d• Teratogenic risk"] S4["💉 Pentamidine
• Alternative systemic agent• Second-line therapy"] START --> ASSESS ASSESS --> LOCAL_PATH ASSESS --> SYSTEMIC_PATH LOCAL_PATH --> LOCAL_OPT SYSTEMIC_PATH --> SYSTEMIC_OPT LOCAL_OPT --> L1 LOCAL_OPT --> L2 LOCAL_OPT --> L3 LOCAL_OPT --> L4 SYSTEMIC_OPT --> S1 SYSTEMIC_OPT --> S2 SYSTEMIC_OPT --> S3 SYSTEMIC_OPT --> S4 style START fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style ASSESS fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style LOCAL_PATH fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SYSTEMIC_PATH fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style LOCAL_OPT fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SYSTEMIC_OPT fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style L1 fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style L2 fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style L3 fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style L4 fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style S1 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style S2 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style S3 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style S4 fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00

flowchart TD Start["🌡️ Suspected Infection
• Assess clinical symptoms• Identify potential source• Fever, leukocytosis, or organ dysfunction"] Empiric["💊 Start Empiric Therapy
• Broad-spectrum coverage• Consider local resistance patterns• Use hospital antibiogram data"] Cultures["🧫 Obtain Cultures
• Blood, urine, or sputum• Collect BEFORE first dose if possible• Gram stain and sensitivity testing"] Review["🔍 Review Culture Data (48-72h)
• Check organism identification• Verify antibiotic sensitivity• Monitor clinical response"] Deescalate["📉 De-escalate or Stop
• Use narrow-spectrum agents• Switch to oral if appropriate• Discontinue if no infection found"] Shortest["⏱️ Shortest Effective Duration
• Minimize toxicity and resistance• Protocol-based treatment lengths• Antimicrobial stewardship completion"] Start --> Empiric Empiric --> Cultures Cultures --> Review Review --> Deescalate Deescalate --> Shortest style Start fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Empiric fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Cultures fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Review fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Deescalate fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Shortest fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["👤 Patient with 'Penicillin Allergy'
• Rule out clinical mislabeling• Document specific reaction history"] Assess{"🔍 Assess Reaction Category
• Determine IgE vs Non-IgE status• Check timing of symptom onset"} IgE["🚨 Anaphylaxis or Urticaria
• IgE-mediated type 1 hypersensitivity• High risk of cross-reactivity"] NonIgE["🩹 Mild Rash (Non-IgE)
• Delayed maculopapular reaction• Low cross-reactivity risk (< 1%)"] Avoid["🚫 Avoid PCN, Cephs, Carbapenems
• Cross-reactivity in R1 side chains• USE: Aztreonam or non-beta-lactams"] Caution["✅ Cautiously Use Cephs/Carbapenems
• Penicillin-skin testing often negative• Monitor for delayed skin reactions"] Start --> Assess Assess -- "Anaphylaxis/Urticaria" --> IgE Assess -- "Mild Rash (Non-IgE)" --> NonIgE IgE --> Avoid NonIgE --> Caution style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Assess fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style IgE fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style NonIgE fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Avoid fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Caution fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD %% Main Title Title["🧫 Bacterial Resistance Strategies
• Mechanisms of antibiotic evasion• Evolution of drug resistance"] %% Path 1: Enzymatic Degradation Path1["✂️ Enzymatic Degradation
• Beta-lactamases hydrolyze drug rings• Inactivates penicillins/cephalosporins• Common in Gram-negative bacteria"] %% Path 2: Target Site Modification Path2["🧬 Target Site Modification
• Alteration of drug binding targets• mecA gene modifying PBPs in MRSA• Prevents antibiotic binding affinity"] %% Path 3: Active Efflux Pumps Path3["📤 Active Efflux Pumps
• Membrane pumps actively expel drugs• Uses ATP or proton motive force• Example: Resistance to Tetracyclines"] %% Path 4: Decreased Permeability Path4["🛡️ Decreased Permeability
• Loss or modification of porin channels• Prevents entry into the cell• Example: Resistance to Carbapenems"] %% Connections Title --- Path1 Title --- Path2 Title --- Path3 Title --- Path4 %% Styles style Title fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Path1 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Path2 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Path3 fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Path4 fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845

flowchart TD Start["💊 Nicotinic Antagonists
• Block ACh at nicotinic receptors• Primarily N-subtypes"] Ganglionic["🏢 Ganglionic Blockers
• Block NN receptors in ganglia• Hexamethonium / Mecamylamine• Impacts ANS outflow"] NMBs["💪 Neuromuscular Blockers (NMBs)
• Block NM receptors at NMJ• Used for surgical relaxation• Interfere with muscle contraction"] NonDepol["🛡️ Non-Depolarizing
• Competitive ACh antagonists• Reversed by Neostigmine• Prevents end-plate potential"] Depol["⚡ Depolarizing
• Persistent end-plate activation• Phase 1 and Phase 2 blocks• Initial fasciculations common"] Curium["🧪 Curonium / Curium Drugs
• Rocuronium, Vecuronium• Long to intermediate duration• Paralysis without fasciculation"] Succinyl["💉 Succinylcholine
• Rapid onset, short duration• Risk of hyperkalemia• Malignant hyperthermia risk"] Start --> Ganglionic Start --> NMBs NMBs --> NonDepol NMBs --> Depol NonDepol --> Curium Depol --> Succinyl style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Ganglionic fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style NMBs fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style NonDepol fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Depol fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Curium fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style Succinyl fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD Start["💊 Empiric Broad-Spectrum IV
• Initiate within 1 hour of sepsis• Cover suspected pathogens• High dose IV administration"] Clinical["🤔 Clinically Improving?
• Resolution of fever/leukocytosis• Hemodynamic stability• Decreased oxygen requirements"] GITract["😋 Functioning GI Tract?
• No nausea or vomiting• Tolerating oral intake/enteral• Normal bowel sounds/motility"] Cultures["🔬 Culture & Sensitivity Results?
• Identification of specific bug• Drug susceptibility testing• Pathogen correlation with site"] SwitchOral["🔄 Switch to Oral Equivalent
• Choose high bioavailability drug• Reduced risk of IV complications• Earlier hospital discharge"] Deescalate["🎯 De-escalate Therapy
• Use narrow-spectrum agent• Reduce collateral damage• Prevent resistance emergence"] Success["✅ Optimized Therapy
• Cost-effective management• Targeted microbial kill• Minimal side effect profile"] Start --> Clinical Start --> Cultures Clinical -- Yes --> GITract GITract -- Yes --> SwitchOral Cultures -- Yes --> Deescalate SwitchOral --> Success Deescalate --> Success style Start fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Clinical fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style GITract fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Cultures fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style SwitchOral fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Deescalate fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Success fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["💊 Atropine Overdose
• Competitive mAChR inhibition• Excessive anticholinergic load• Classic toxidrome risk"] Antidote["🧪 Antidote: Physostigmine
• Acetylcholinesterase inhibitor• Crosses blood-brain barrier• Competitive reversal of blockade"] Main["⚡ Widespread Muscarinic Blockade
• Blocked postganglionic parasymp.• Prevents ACh binding• Multi-organ system involvement"] CNS["🧠 CNS Effects
• Delirium and confusion• Visual hallucinations• 'Mad as a hatter' symptoms"] Periph["🫀 Peripheral Effects
• Tachycardia and Myidriasis• Fever and dry skin• 'Hot as a hare, blind as a bat'"] Start --> Main Antidote -- Reverses --> Main Main --> CNS Main --> Periph style Start fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Antidote fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Main fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style CNS fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Periph fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845

flowchart TD subgraph Presynaptic_Neuron [Presynaptic Neuron] Choline["🧪 Choline
• Primary precursor for ACh• Recycled from cleft via reuptake"] ACoA["⚡ Acetyl-CoA
• Metabolic intermediate• Derived from mitochondria"] Synthesis["🔬 Synthesis
• Catalyzed by ChAT enzyme• Occurs in the cytoplasm"] ACh_Pre["💊 Acetylcholine (ACh)
• Primary neurotransmitter• Reaches terminal for storage"] Vesicle["📦 Vesicle Storage
• Protected from degradation• Loaded via VAT transporter"] Release["🚀 Neurotransmitter Release
• Dependent on Ca2+ influx• Exocytosis at active zone"] end subgraph Synaptic_Cleft [Synaptic Cleft] ACh_Cleft["🌟 ACh in Cleft
• Binds to post-synaptic receptors• Brief half-life in synapse"] Degradation["✂️ Breakdown (AChE)
• Acetylcholinesterase enzyme• Yields Choline + Acetate"] end Choline -->|Choline Transporter| Synthesis ACoA --> Synthesis Synthesis -->|ChAT| ACh_Pre ACh_Pre -->|VAT| Vesicle Vesicle -->|Ca2+ Influx| Release Release --> ACh_Cleft ACh_Cleft -->|AChE| Degradation Degradation -->|Reuptake| Choline style Choline fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style ACoA fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style Synthesis fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style ACh_Pre fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style Vesicle fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style Release fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style ACh_Cleft fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style Degradation fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD START["💊 Neuromuscular Blockers
• Used for surgical paralysis• Target Nicotinic ACh receptors• Monitor with Train-of-Four (TOF)"] NON_DEP["🚫 Non-Depolarizing
• Competitive antagonists• Reversible by AChE inhibitors• Show progressive fade on TOF"] DEP["⚡ Depolarizing
• Agonist leads to persistent depolarization• Two distinct clinical phases• High risk of hyperkalemia"] CURONIUM["🧪 Curoniums
• Vecuronium, Rocuronium• Intermediate to long duration• Hepatic and renal clearance"] CURIUM["🧪 Curiums
• Atracurium, Cisatracurium• Hofmann elimination (spontaneous)• Safe in renal or hepatic failure"] SUCC["💉 Succinylcholine
• Rapid onset and short duration• Metabolized by pseudocholinesterase• Causes initial muscle fasciculation"] FADE["📉 TOF: Fade
• Progressive decreased twitch response• Characteristic of Non-Depolarizing• Post-tetanic facilitation seen"] PHASE1["📊 Phase I Block
• Constant but diminished response• No fade during TOF stimulation• Potentiated by AChE inhibitors"] PHASE2["📉 Phase II: Desensitization
• Happens with prolonged exposure• Fade response resembling Non-Depolarizing• ACh receptors become unresponsive"] START --> NON_DEP START --> DEP NON_DEP -- Competitive Antagonist --> CURONIUM NON_DEP -- Competitive Antagonist --> CURIUM NON_DEP --> FADE DEP -- Agonist leads to Persistent Depolarization --> SUCC DEP --> PHASE1 DEP --> PHASE2 style START fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style NON_DEP fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style DEP fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style CURONIUM fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style CURIUM fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style SUCC fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style FADE fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style PHASE1 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style PHASE2 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00

flowchart TD Start["🚨 Organophosphate Exposure
• Pesticides or nerve agents• Dermal or inhalation route"] AChE["⚠️ AChE Inhibition
• Irreversible binding to enzyme• Enzyme 'aging' over time"] HighACh["🧪 High Acetylcholine
• Accumulation at synaptic cleft• Cholinergic toxicity state"] Overload["🧬 Receptor Overload
• Muscarinic receptor activation• Nicotinic receptor activation"] DUMBBELSS["🤮 Muscarinic Effects
• DUMBBELSS: Diarrhea, Urination• Miosis, Bradycardia, Emesis• Lacrimation, Salivation, Sweating"] MuscleP["💪 Nicotinic Effects
• Muscle fasciculations• Eventual flaccid paralysis• Tachycardia early on"] Treatment["💊 Treatment Options
• Reverse toxic symptoms• Prevent enzyme aging"] Atropine["💉 Atropine
• Competitive mAChR antagonist• Reverses DUMBBELSS only"] Pralidoxime["🧪 Pralidoxime (2-PAM)
• Regenerates active AChE• Works at NMJ if given early"] Start --> AChE AChE --> HighACh HighACh --> Overload Overload -- Muscarinic --> DUMBBELSS Overload -- Nicotinic --> MuscleP Treatment --- Atropine Treatment --- Pralidoxime style Start fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style AChE fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style HighACh fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Overload fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style DUMBBELSS fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style MuscleP fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Treatment fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Atropine fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style Pralidoxime fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD subgraph LoopOfHenle ["🔄 Loop of Henle Mechanism"] Start["💧 Descending Limb Entrance
• Isotonic filtrate enters from PCT• Osmolality approx. 300 mOsm/kg"] Passive["🧪 Passive Reabsorption
• H2O moves out via osmosis• Concentrates the tubular filtrate• Impermeable to solutes/NaCl"] Active["⚡ Thick Ascending Limb (TAL)
• Active transport of Na-K-2Cl• NaCl reabsorbed into interstitium• Dilutes filtrate (hypotonic)"] end subgraph Interstitium ["🏥 Renal Interstitium"] Medulla["📈 High Medullary Osmolality
• Vertical osmotic gradient created• Essential for urine concentration• Reaches up to 1200 mOsm/kg"] end Start --> Passive Passive --> Active Active -->|pumps ions into| Medulla Medulla -->|draws water from| Passive style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Passive fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Active fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Medulla fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD LOH["🧬 Loop of Henle Creates Gradient
• Countercurrent multiplier system• Reabsorbs Sodium in thick segment• Establishes medullary hypertonicity"] VR["🩸 Vasa Recta Maintains Gradient
• Countercurrent exchange mechanism• Slow blood flow prevents washout• High permeability to water and salt"] CONC["💧 Enables Urine Concentration
• Facilitates water reabsorption• ADH acts on collecting ducts• Produced urine is hyperosmotic"] LOH --> VR VR --> CONC style LOH fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style VR fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style CONC fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD subgraph TAL_Cell ["Thick Ascending Limb (TAL) Environment"] Lumen["💧 Lumen Fluid
• Primary source of electrolytes• Target of Loop Diuretics"] ATPase["⚡ Na+/K+ ATPase
• Basolateral localization• Establishes low intra-cell Na+• Consumes ATP for transport"] Influx["🔄 Electrolyte Entry
• NKCC2 symporter action• Moves Na+, K+, and 2Cl-• Electroneutral transport"] Solutes["📈 Medullary Solutes
• Countercurrent multiplication• Increases corticomedullary gradient• Facilitates water reabsorption"] Potential["➕ Lumen-Positive Potential
• K+ back-leak into lumen• ROMK channel mediated• Creates electrical driving force"] end Paracellular["💎 Cation Reabsorption
• Driven by positive lumen charge• Reabsorbs Ca2+ and Mg2+• Occurs via paracellular pathway"] %% Connections Lumen -- "NKCC2" --> Influx ATPase -- "Maintains Na+ Gradient" --> Influx Influx -- "Basolateral Transporters" --> Solutes Influx -- "K+ Leak Channel" --> Potential Potential -- "Drives" --> Paracellular %% Styling style Lumen fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style ATPase fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Influx fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Solutes fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Potential fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Paracellular fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD START["🧠 ADH Dysregulation
• Impaired water balance regulation• Target: Collecting duct V2 receptors• Control of serum osmolality"] SIADH["💧 SIADH: High ADH
• Excessive hormone secretion• Inappropriate water retention• Euvolemic presentation"] DI["🏜️ DI: Low ADH/Response
• Central: Lack of production• Nephrogenic: Renal resistance• Characterized by polyuria"] SIADH_RES["⚠️ High H2O Reabsorption
• Hyponatremia (Dilutional)• High urine osmolality > 100• High urine Na+ > 40 mEq/L"] DI_RES["⚠️ Low H2O Reabsorption
• Serum Hypernatremia• Dilute urine (Low SG)• Extreme thirst (Polydipsia)"] START --> SIADH START --> DI SIADH --> SIADH_RES DI --> DI_RES style START fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style SIADH fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style DI fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style SIADH_RES fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style DI_RES fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000

flowchart TD POP["👥 Population Without Disease
• Prospective cohort selection• All subjects must be at risk• Free of outcome at baseline"] EXP["🔍 Exposure Status
• Classification of subjects• Defines the study groups• Observation-based grouping"] FOLLOW_E["⏳ Follow Over Time (Exposed)
• Longitudinal observation• Assessment of incidence• Monitor for outcome onset"] FOLLOW_U["⏳ Follow Over Time (Unexposed)
• Control group observation• Baseline risk comparison• Identical monitoring period"] OUT["🎯 Outcome?
• Calculate Relative Risk (RR)• Compare incidence rates• Identify risk associations"] POP --> EXP EXP -- Exposed --> FOLLOW_E EXP -- Unexposed --> FOLLOW_U FOLLOW_E --> OUT FOLLOW_U --> OUT style POP fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style EXP fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style FOLLOW_E fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style FOLLOW_U fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style OUT fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD START["🔍 Choose Exposure?
• Investigator assigns exposure• Controlled intervention• No randomization = Quasi"] EXP_DESIGN["🧪 Experimental Design
• Randomized Clinical Trials• Testing efficacy and safety• Highest level of control"] OBS_DESIGN["🔬 Observational Design
• No investigator intervention• Naturally occurring exposure• Useful for ethical limits"] FOLLOW_TIME["⏳ Followed in Time?
• Longitudinal assessment• Tracking over duration• Followed from exposure to event"] OTHER_STUDY["📋 Non-Cohort Studies
• Cross-Sectional (Snapshot)• Case-Control (Outcome first)• Ecological (Populations)"] COHORT_ROOT["👥 Cohort Study
• Group defined by exposure• Outcome is currently absent• Calculates Relative Risk"] PROSPECTIVE["🚀 Prospective Cohort
• Followed into the future• Concurrent data collection• Direct incident tracking"] RETROSPECTIVE["📜 Retrospective Cohort
• Uses historical records• Both exposure/outcome passed• Faster/cheaper to conduct"] MIXED["🔄 Mixed Cohort Study
• Combined design approach• Ambidirectional timeline• Historical + future follow-up"] START -- Yes --> EXP_DESIGN START -- No --> OBS_DESIGN OBS_DESIGN --> FOLLOW_TIME FOLLOW_TIME -- No --> OTHER_STUDY FOLLOW_TIME -- Yes --> COHORT_ROOT COHORT_ROOT -.-> PROSPECTIVE COHORT_ROOT -.-> RETROSPECTIVE COHORT_ROOT -.-> MIXED style START fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style EXP_DESIGN fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style OBS_DESIGN fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style FOLLOW_TIME fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style OTHER_STUDY fill:#F5F5F5, stroke:#9E9E9E, stroke-width:2px, color:#212121 style COHORT_ROOT fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style PROSPECTIVE fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style RETROSPECTIVE fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style MIXED fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845

flowchart TD START["🩸 Anemia Evaluation
• Check Hemoglobin and Hematocrit• Assess for symptoms of tissue hypoxia• Evaluate RBC indices (MCV, MCH)"] MCV["📏 Check MCV Level
• Microcytic: MCV less than 80 fL• Normocytic: MCV 80 to 100 fL• Macrocytic: MCV greater than 100 fL"] RETIC["🔍 Reticulocyte Count
• Assesses bone marrow response• Corrected index helps guide diagnosis• Distinguishes production vs loss"] SMEAR["🔬 Peripheral Blood Smear
• Check morphology (Schistocytes/Spherocytes)• Identify abnormal cell types• Rule out artifacts or clumping"] DIAG["🩺 Final Differential Diagnosis
• Correlate with iron studies or B12• Consider occult bleeding or hemolysis• Finalize management plan"] START --> MCV MCV --> RETIC RETIC --> SMEAR SMEAR --> DIAG style START fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style MCV fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style RETIC fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style SMEAR fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style DIAG fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["📉 Low Serum Ca2+
• Hypocalcemia trigger• Sensed by Ca-sensing receptors"] PTH["⬆️ Increased PTH
• Parathyroid gland response• Rapid hormone secretion"] subgraph KidneyPanel [Kidney Effects] CaReabs["⬆️ Ca2+ Reabsorption
• Distal Convoluted Tubule• Decreases renal Ca2+ loss"] PO4Reabs["⬇️ PO4 3- Reabsorption
• Proximal Tubule effect• Increases phosphate excretion"] Calcitriol["⬆️ Calcitriol
• 1-alpha-hydroxylase stimulus• Active Vitamin D synthesis"] end Start --> PTH PTH --> CaReabs PTH --> PO4Reabs PTH --> Calcitriol style Start fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style PTH fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style KidneyPanel fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style CaReabs fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style PO4Reabs fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Calcitriol fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD subgraph KR["KEY REGULATORS"] K_High["🧪 High Plasma K+
• Hyperkalemia trigger• Direct adrenal stimulation• Normal range: 3.5-5.0 mEq/L"] ALDO["🧂 Increased Aldosterone
• Mineralocorticoid hormone• From adrenal zona glomerulosa• Regulates Na/K balance"] end subgraph PCR["PRINCIPAL CELL RESPONSE"] PUMP["⚡ Increased Basolateral Na+/K+ Pump
• Active transport mechanism• High K+ uptake into cell• Driven by ATP hydrolysis"] CHAN["💧 Increased Apical ENaC and K+ Channels
• Epithelial Sodium Channels (ENaC)• ROMK channels for K+ efflux• Facilitated diffusion pathway"] end SEC["✅ Increased K+ Secretion
• Occurs in Distal Tubule/CD• Final urinary excretion• Restores plasma homeostasis"] %% Connections K_High --> ALDO K_High --> PUMP ALDO --> PUMP ALDO --> CHAN PUMP --> SEC CHAN --> SEC %% Styling style K_High fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style ALDO fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style PUMP fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style CHAN fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style SEC fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A style KR fill:#F5F5F5,stroke:#333,stroke-dasharray: 5 5 style PCR fill:#F5F5F5,stroke:#333,stroke-dasharray: 5 5

flowchart TD START["⚡ JGA Triggers
• Decreased Renal Perfusion• Decreased NaCl at Macula Densa• Increased Sympathetic Tone"] JGA["🔬 JGA Activation
• Juxtaglomerular Cells• Located in Afferent Arteriole• Baroreceptor function"] RENIN_REL{"💧 Renin Release
• Proteolytic enzyme• Rate limiting step"} LIVER["🥩 Angiotensinogen
• Produced by Liver• Alpha-2-globulin• Circulates in plasma"] ANG_I["🧬 Angiotensin I
• Decapeptide• Minimal biologic activity• Formed in circulation"] ANG_II["💥 Angiotensin II
• Potent vasoconstrictor• Stimulates Aldosterone• Increases thirst/ADH"] START --> JGA JGA --> RENIN_REL RENIN_REL --> LIVER LIVER -- Renin --> ANG_I ANG_I -- "ACE (in lungs)" --> ANG_II style START fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style JGA fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style RENIN_REL fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style LIVER fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style ANG_I fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style ANG_II fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD PT["💧 Proximal Tubule
• Mg2+ Reabsorption: 15-25%• Driven by Na/water reabsorption• Passive paracellular transport"] TAL["⚡ Thick Ascending Limb
• Mg2+ Reabsorption: 60-70%• Major site of regulated transport• Uses Claudin-16 and Claudin-19"] DT["🧪 Distal Tubule
• Mg2+ Reabsorption: 5-10%• Active transcellular transport• TRPM6 channels involved"] PT --> TAL TAL --> DT style PT fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style TAL fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style DT fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754

flowchart TD Fresh["🌱 Fresh Stage: Autolysis
• Timeline: 0-24 hours after death• Enzymatic self-digestion of cells• Algor, Livor, and Rigor mortis set in"] Bloat["🎈 Bloat Stage: Putrefaction
• Timeline: 24-72 hours after death• Anaerobic bacteria produce gases• Swelling and odor development"] Active["🪱 Active Decay: Colliquative
• Timeline: 1-3 weeks after death• Rapid mass loss and liquefaction• Peak insect activity (maggots)"] Advanced["💧 Advanced Decay: Fermentation
• Timeline: 3 weeks - 2 months• Butyric fermentation occurs• Tissues dry out; cheesy odor"] Dry["🦴 Dry Remains: Skeletalisation
• Timeline: More than 2 months• Only dry skin, cartilage, and bone• Bleaching of bones if exposed"] Fresh --> Bloat Bloat --> Active Active --> Advanced Advanced --> Dry style Fresh fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Bloat fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Active fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Advanced fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Dry fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD START["🔍 Cutaneous Assessment
• Evaluate skin manifestation• Assess clinical severity• Check for systemic involvement"] STRAT["⚖️ Treatment Strategy
• Risk stratification• Symptom-based approach• Escalation planning"] MILD["🧴 Lifestyle and Topical
• Emollients and humectants• Topical antipruritics• Low-potency steroids• Systemic antihistamines"] MOD["🎯 Targeted Therapy
• Potent topical steroids• Intralesional steroids• Hydroxychloroquine first-line"] SEVERE["💊 Systemic Modulation
• Prednisone 0.5-1 mg/kg/day• Azathioprine/Mycophenolate• Biologics (e.g. Rituximab)"] START --> STRAT STRAT -- "Xerosis / Pruritus" --> MILD STRAT -- "Annular Erythema / Mild Vasculitis" --> MOD STRAT -- "Severe Vasculitis / Refractory" --> SEVERE style START fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style STRAT fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style MILD fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style MOD fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style SEVERE fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD START["🩸 Low Renal Perfusion
• Occurs in Kidney JGA cells• Response to low BP/Na+• Triggers RAAS activation"] RENIN["🧪 Renin Release
• Enzyme secreted by kidneys• Cleaves Angiotensinogen• Rate-limiting RAAS step"] LIVER["🧬 Angiotensinogen
• Produced by the Liver• Circulating plasma protein• Precursor to Angiotensin I"] ANG1{"💎 Angiotensin I
• Formed in systemic blood• Mild vasoconstrictor properties• Substrate for ACE enzyme"} ACE["🫁 ACE (Lungs)
• Angiotensin Converting Enzyme• Located in lung endothelium• Target of ACE inhibitors"] ANG2["🔥 Angiotensin II
• Potent peptide hormone• Binds AT1 receptors• Rapidly increases BP"] VASO["⚙️ Increased Vasoconstriction
• Increases Systemic Resistance• Constricts efferent arterioles• Immediate BP elevation"] ALDO["🧂 Increased Aldosterone
• From Adrenal Cortex (Glomerulosa)• Increases Na+/H2O retention• Long-term volume expansion"] START --> RENIN RENIN --> ANG1 LIVER --> ANG1 ANG1 -- "ACE Catalysis" --> ACE ACE --> ANG2 ANG2 --> VASO ANG2 --> ALDO style START fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style RENIN fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style LIVER fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style ANG1 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style ACE fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style ANG2 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style VASO fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style ALDO fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD Perfusion["🔻 Low Renal Perfusion
• Sensed by baroreceptors• Occurs in afferent arteriole• Triggered by hypotension"] NaCl["🧂 Low NaCl at Macula Densa
• Distal tubule sodium sensing• Prostaglandin signal• Reflects low GFR"] Symp["🧠 Sympathetic Stimulation
• Via Beta-1 receptors• Stress or blood loss• Norepinephrine action"] JG_Cells{"🔬 Juxtaglomerular Cells
• Modified smooth muscle• Arteriole wall location• Hormone synthesis site"} Renin["✅ High Renin Secretion
• Rate-limiting RAAS step• Cleaves Angiotensinogen• Result: Increased BP"] Perfusion --> JG_Cells NaCl --> JG_Cells Symp --> JG_Cells JG_Cells --> Renin style Perfusion fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style NaCl fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Symp fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style JG_Cells fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Renin fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD subgraph PrincipalCell ["Principal Cell Mechanisms"] StartALDO["💧 Aldosterone
• Steroid hormone from adrenal cortex• Binds mineralocorticoid receptors"] StartADH["🧠 ADH (Vasopressin)
• Released from posterior pituitary• Responds to high serum osmolarity"] Nucleus["🧬 Nucleus Action
• Gene transcription activated• Protein synthesis initiated"] V2Rec["G-Protein Receptor
• V2 Receptor activation• Gs pathway coupling"] Synthesis["🛠️ Synthesis Phase
• Increased ENaC synthesis• Increased ROMK synthesis"] CAMP["⚡ Increased cAMP
• Adenylate cyclase activation• Protein Kinase A (PKA) signaling"] IonFlux["⚡ Ion Transport
• Increased Na+ Influx• Increased K+ Efflux (secretion)"] AQP2["🚰 AQP2 Insertion
• Aquaporin-2 vesicle translocation• Apical membrane expression"] H2OReab["🌊 Water Reabsorption
• Increased H2O permeability• Concentrates urine output"] end StartALDO --> Nucleus Nucleus --> Synthesis Synthesis --> IonFlux StartADH --> V2Rec V2Rec --> CAMP CAMP --> AQP2 AQP2 --> H2OReab style StartALDO fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style StartADH fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style Nucleus fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style V2Rec fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style Synthesis fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style CAMP fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style IonFlux fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style AQP2 fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style H2OReab fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD ANG2["🧪 Angiotensin II
• Potent vasoconstrictor hormone• Key component of RAAS system• Derived from Angiotensin I via ACE"] AT1R["🧬 AT1 Receptor
• G-protein coupled receptor• Mediates most known effects of Ang II• Target of ARB medications"] SQUEEZE["🩺 Squeeze: Vasoconstriction
• Increased Systolic and Diastolic BP• Increased Total Peripheral Resistance• Rapid systemic response"] SALT["🧂 Salt: Aldosterone Release
• Increased Na+ and H2O Retention• Acts on Adrenal Cortex Zona Glomerulosa• Increases blood volume"] SIP["💧 Sip: ADH and Thirst
• Increased H2O Retention in kidneys• Stimulates thirst centers in brain• Increases free water reabsorption"] SYMP["⚡ Sympathetic Activity
• Increased HR and Contractility• Potentiates Norepinephrine release• Increases Cardiac Output"] SCAR["🕸️ Scarring: Hypertrophy
• Vascular and Cardiac Remodeling• Myocyte growth and fibroblast activation• Long-term structural damage"] GFR["🛡️ Save GFR: Efferent Constriction
• Maintains Glomerular Filtration• Preferential action on Efferent Arteriole• Increases intraglomerular pressure"] ANG2 --> AT1R AT1R --> SQUEEZE AT1R --> SALT AT1R --> SIP AT1R --> SYMP AT1R --> SCAR AT1R --> GFR style ANG2 fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style AT1R fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style SQUEEZE fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style SALT fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style SIP fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style SYMP fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style SCAR fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style GFR fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD A["🧬 Angiotensinogen
• Alpha-2-globulin precursor• Produced in the liver• Circulates in plasma"] R{"🧪 Renin Enzyme
• Released by JG cells• Rate-limiting step• Stimulated by low BP"} B["💉 Angiotensin I
• Decapeptide molecule• Mild vasoconstrictor• Rapidly converted to ATII"] A --> R R --> B style A fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style R fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style B fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["🩺 Suspected RMS
• Rhabdomyosarcoma suspicion• Most common pediatric STS• Rapidly growing painless mass"] Biopsy{"🔬 Biopsy + IHC
• Immunohistochemistry focus• Essential for histotype• Core or incisional preferred"} Imaging{"🖼️ Imaging
• Assess local extension• Identify distant spread• Baseline for response"} Staging["📊 Staging Workup
• Systemic assessment• Risk stratification• Guides therapy intensity"] Markers["🧪 Key Markers: Myogenin, MyoD1
• Skeletal muscle lineage• Nuclear staining pattern• High sensitivity/specificity"] Confirm["✅ Confirm & Stage: IRS/TNM
• Intergroup Rhabdomyosarcoma• Surgical-pathologic grouping• Site-size-node staging"] Primary["📍 MRI/CT (Primary)
• MRI for head/neck/extremity• CT for chest/abdomen• Evaluate vessel proximity"] Metastasis["✈️ PET-CT / CT Chest
• Lung is primary met site• Whole body PET evaluation• Lymph node involvement"] Systemic["🦴 Bone Marrow Bx, CSF
• CSF if parameningeal site• Bilateral BM aspirates• Rule out stage 4 disease"] Start --> Biopsy Start --> Imaging Start --> Staging Biopsy -- Key Markers --> Markers Biopsy --> Confirm Imaging -- Primary --> Primary Imaging -- Metastasis --> Metastasis Imaging --> Confirm Staging --> Confirm Staging --> Systemic style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Biopsy fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Imaging fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Staging fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Markers fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Confirm fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style Primary fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Metastasis fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Systemic fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845

flowchart TD Start["👶 Suspect EA/TEF
• Presentation: Choking and coughing• Clinical: Frothy saliva and drooling• Trigger: Cyanosis during feeds"] NGPassage{"👃 Attempt NG Tube
• Bedside diagnostic attempt• Use firm radiopaque catheter"} XRay["📸 Chest and Abdominal X-ray
• Primary imaging modality• Visualize catheter tip position"] ConfirmDx{"✅ Confirm Diagnosis
• Finding: Coiled NG tube in pouch• Bowel gas: Suggests distal TEF• No gas: Suggests isolated EA"} InitialRx["🏥 Initial Management (Rx)
• NPO and IV hydration• Continuous pouch suction• Position: Head up 30 deg"] Surgery["👨‍⚕️ Surgical Consult
• Urgent pediatric surgery referral• Pre-op echo for aortic arch side"] Start --> NGPassage NGPassage -- "Fails to pass / Coils" --> XRay XRay --> ConfirmDx ConfirmDx --> InitialRx InitialRx --> Surgery style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style NGPassage fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style XRay fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style ConfirmDx fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style InitialRx fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Surgery fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["🔍 Precocious Puberty Signs
• Girls: Secondary sex traits before 8y• Boys: Secondary sex traits before 9y• Rapid growth/linear acceleration"] Step1{"🧪 Initial Evaluation
• Bone Age X-ray (Left hand/wrist)• Basal LH and FSH levels• Advanced BA = >2SD above chronological"} GNRH_TEST{"💉 GnRH Stimulation Test
• Administer Leuprolide or GnRH• Measure LH response at 30/60 min• Gold standard for CPP vs PPP"} CPP["🧠 Central PP (GnRH-dependent)
• Early activation of HPO axis• High/Pubertal basal or stim LH• Usually idiopathic in girls"] PPP["🎗️ Peripheral PP (GnRH-independent)
• Excess sex steroids from other source• Low/Prepubertal LH response• Adrenal or gonadal pathology"] MRI["📷 Cranial MRI
• Evaluate Hypothalamic region• R/O Hamartomas or Neoplasms• High priority in boys and young girls"] INVESTIGATE["🔬 Peripheral Workup
• USG Adrenals and Gonads• DHEAS, Testosterone, Estrogen• Check for MCC-Albright syndrome"] RX_CPP["💊 Rx: GnRH Agonist
• Continuous stimulation desensitizes• Preserves final adult height• Reversible upon discontinuation"] RX_PPP["🏥 Rx: Treat Underlying Cause
• Surgery for tumors• Corticosteroids for CAH• Blockers for McCune-Albright"] Start --> Step1 Step1 -- "Advanced Bone Age and Pubertal LH" --> CPP Step1 -- "Advanced Bone Age and Prepubertal LH" --> GNRH_TEST GNRH_TEST -- "Pubertal LH Response" --> CPP GNRH_TEST -- "Prepubertal LH Response" --> PPP CPP --> MRI MRI --> RX_CPP PPP --> INVESTIGATE INVESTIGATE --> RX_PPP style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Step1 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style GNRH_TEST fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style CPP fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style PPP fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style MRI fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style INVESTIGATE fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style RX_CPP fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style RX_PPP fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD START["🔍 Suspected HIV in Child
• Clinical suspicion or exposure• Universal screening for infants"] AGE{👶 Age Assessment
• Under 18 months vs Over 18 months} PCR["🧬 Virological Tests: HIV DNA/RNA PCR
• Maternal antibodies persist in infants• Standard for vertical transmission"] AB_TEST["💉 HIV Antibody Test
• ELISA or Rapid test formats• Maternal antibodies should be gone"] RES1{📊 PCR Result?} RES2{📊 Antibody Result?} REPEAT["🔁 Repeat Virological Test
• Confirmation of first PCR result• Mandatory before ART initiation"] MONITOR["🩺 Monitor and Re-test
• Re-test if high risk/symptoms• Monitor growth and development"] CONFIRM["✅ Confirmatory Antibody Test
• e.g. Western Blot or alternate kit• Formalizes diagnosis for adults/older kids"] UNLIKELY["🛡️ HIV Unlikely
• Assumes no recent exposure• Negative result beyond window period"] HIV_OK["🚨 HIV Confirmed
• Link to pediatric HIV care• Immediate clinical evaluation"] START --> AGE AGE -- "Under 18 months" --> PCR AGE -- "Over 18 months" --> AB_TEST PCR --> RES1 RES1 -- Positive --> REPEAT RES1 -- Negative --> MONITOR AB_TEST --> RES2 RES2 -- Positive --> CONFIRM RES2 -- Negative --> UNLIKELY REPEAT -- Positive --> HIV_OK CONFIRM -- Positive --> HIV_OK style START fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style AGE fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style PCR fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style AB_TEST fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style RES1 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style RES2 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style REPEAT fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style MONITOR fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style CONFIRM fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style UNLIKELY fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style HIV_OK fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD START["📋 Initial Evaluation
• Perform CBC, BMP, and Urinalysis• OB consultation and Fetal Monitoring• Renal bladder Ultrasound (RBUS)"] OBSTRUCT["🔍 Obstructing Stone?
• Confirmed via ultrasound imaging• Identify hydroureteronephrosis"] COMP_FACTORS["⚠️ Acute Complicating Factors
• UTI + Fever > 101.5 or Instability• Oliguric or anuric renal failure• AKI or intractable pain/vomiting"] DECIDE_1{"Complicating Factors?"} DECIDE_2{"Complicating Factors?"} INTERVENTION["🛠️ Interventional Guidelines
• Consult Urology for drainage• Consider stent or nephrostomy"] CONSERVATIVE["💊 Conservative Management
• Pain control and anti-emetics• Alpha-blocker and strain urine• Serial creatinine monitoring"] SECOND_LINE["📸 Second Line Imaging
• Low-dose CT or MR Urogram• Evaluate for occult pathology"] DISCHARGE["✅ Discharge & Referral
• Discharge when symptoms stable• Referral to Endourology"] START --> OBSTRUCT OBSTRUCT -- "Yes" --> DECIDE_1 OBSTRUCT -- "No" --> DECIDE_2 DECIDE_1 -- "Yes" --> INTERVENTION DECIDE_1 -- "No" --> CONSERVATIVE DECIDE_2 -- "Yes" --> SECOND_LINE DECIDE_2 -- "No" --> CONSERVATIVE CONSERVATIVE --> DISCHARGE CONSERVATIVE -.-> OBSTRUCT style START fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style OBSTRUCT fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style COMP_FACTORS fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style DECIDE_1 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style DECIDE_2 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style INTERVENTION fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style CONSERVATIVE fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SECOND_LINE fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style DISCHARGE fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["💉 Beta-Agonists
• Sympathomimetic agents• Bind G-protein receptors• Increase cAMP levels"] NonSel["⚖️ Non-Selective (beta1 = beta2)
• Equal affinity for both receptors• Isoproterenol (Prototype)• Significant HR increase"] Beta1Sel["❤️ Beta1-Selective (beta1 > beta2)
• Predominantly cardiac effect• Dobutamine (Main agent)• Increases contractility (+ Inotropy)"] Beta2Sel["🫁 Beta2-Selective (beta2 > beta1)
• Bronchodilation focus• Smooth muscle relaxation• Used in Asthma and COPD"] Alb["🌬️ Albuterol
• SABA (Short-acting)• Acute rescue inhaler"] Salm["⏱️ Salmeterol
• LABA (Long-acting)• Maintenance therapy"] Terb["🤰 Terbutaline
• SABA/Tocolytic agent• Reduces uterine contractions"] Start --> NonSel Start --> Beta1Sel Start --> Beta2Sel Beta2Sel --> Alb Beta2Sel --> Salm Beta2Sel --> Terb style Start fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style NonSel fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Beta1Sel fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Beta2Sel fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Alb fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Salm fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Terb fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00

flowchart TD Start["🚨 Tumor Catecholamine Surge
• Excess Epi and Norepi release• Risks hypertensive crisis• Triggers: stress or palpation"] ControlBP{"⚖️ Control BP?
• Goal: SBP < 130 mmHg• Goal: DBP < 80 mmHg• Prevent perioperative stroke"} AlphaBlock["💊 Alpha-Adrenergic Blockade
• Start Phenoxybenzamine first• 7 to 14 days pre-op duration• Prevents unopposed alpha vasoconstriction"] BetaBlock["💓 Beta-Adrenergic Blockade
• Add ONLY after alpha blockade• Controls reflex tachycardia• Helps manage arrhythmias"] Surgery["🔪 Surgery
• Laparoscopic Adrenalectomy• Ensure volume expansion• Monitor for post-op hypotension"] Start --> ControlBP ControlBP --> AlphaBlock AlphaBlock --> BetaBlock BetaBlock --> Surgery style Start fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style ControlBP fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style AlphaBlock fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style BetaBlock fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Surgery fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD Agonist["💊 Beta-Agonist
• Ligand binding (e.g. Albuterol)• Sympathomimetic effect"] Receptor["🧬 Beta-Receptor
• G protein-coupled receptor• 7-transmembrane domains"] GsProtein["🔋 Increased Gs Activity
• GDP to GTP exchange• Alpha-s subunit dissociation"] ACyclase["⚡ Increased Adenylyl Cyclase
• Enzyme activation on membrane• Signal amplification step"] cAMP["🧪 Increased cAMP
• Conversion of ATP to cAMP• Secondary messenger surge"] PKA["🔑 Increased Protein Kinase A
• cAMP binds regulatory subunits• Releases active catalytic PKA"] Phospho["✨ Protein Phosphorylation
• Modification of target proteins• ATP used as phosphate donor"] Response["🎯 Cellular Response
• Bronchodilation (beta-2)• Increased Heart Rate (beta-1)"] Agonist --> Receptor Receptor --> GsProtein GsProtein --> ACyclase ACyclase -- ATP --> cAMP cAMP --> PKA PKA --> Phospho Phospho --> Response style Agonist fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style Receptor fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style GsProtein fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style ACyclase fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style cAMP fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style PKA fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style Phospho fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style Response fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD subgraph Alpha_Antagonist_Action [Alpha Antagonist Action] Start["💊 Alpha Antagonist
• Examples: Prazosin, Terazosin• Competitive inhibition• Used for HTN and BPH"] Block["🛡️ Blocks alpha1 Receptor
• Prevents NE/Epi binding• Gq protein signaling inhibition• Decreased PLC/IP3 pathway"] end subgraph Physiological_Effect [Physiological Effect] DecreaseContraction["💪 Decreased Smooth Muscle Contraction
• Reduced intracellular Calcium• Relaxation of vascular walls• Relaxed prostate smooth muscle"] Vasodilation["⭕ Vasodilation
• Peripheral resistance decreases• Arterial and venous dilation• Orthostatic risk increases"] DecreaseBP["📉 Decreased Blood Pressure
• Effective antihypertensive effect• Watch for first-dose syncope• Reflex tachycardia possible"] end Start --> Block Block --> DecreaseContraction DecreaseContraction --> Vasodilation Vasodilation --> DecreaseBP style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Block fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style DecreaseContraction fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Vasodilation fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style DecreaseBP fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["DRUG: Phenylephrine
• Selective alpha-1 agonist• Minimal beta activity• Pure vasopressor agent"] Vasocon["Increased BP
• Alpha-1 vasoconstriction• Increased SVR• Systemic arterial press"] Baro["Baroreceptor Activation
• Carotid sinus stretch• Aortic arch receptors• Negative feedback loop"] Vagal["Increased Vagal Firing
• Parasympathetic stimulus• CN X activation• Decreased SNS outflow"] Outcome["Decreased Heart Rate
• Reflex bradycardia• SA node inhibition• Compensatory mechanism"] Start --> Vasocon Vasocon --> Baro Baro --> Vagal Vagal --> Outcome style Start fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style Vasocon fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style Baro fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style Vagal fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style Outcome fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD START["💊 Sympathomimetic Overdose
• Examples: Cocaine, Amphetamines• Signs: Tachycardia, Mydriasis• Risk: Hyperthermia and Seizures"] DECISION{"⚠️ Severe Hypertension?
• BP typically >180/120 mmHg• Check for end-organ damage"} LABETALOL["🏥 Alpha/Beta-blocker
• Example: Labetalol administration• Provides combined blockade• Avoid pure beta-blockers"] SUPPORT["🧘 Supportive Care
• Administer Benzodiazepines• IV fluids and cooling• Cardiac monitoring required"] START --> DECISION DECISION -- Yes --> LABETALOL DECISION -- No --> SUPPORT style START fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style DECISION fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style LABETALOL fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SUPPORT fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD StartNode["📝 Preamble and Consent
• Formal introduction and purpose• Obtain informed written consent• Explain right to refuse/withdraw"] HistoryNode["🗣️ History Taking
• Document exact sequence of events• Note relevant previous medical history• Record verbatim quotes where applicable"] ExamNode["🔍 Clinical Exam and Injury Documentation
• Systematic physical assessment• Detailed injury mapping and charting• Photographic evidence collection"] InvestNode["🧪 Necessary Investigations
• Forensic lab samples (swabs/DNA)• Imaging (Radiology/Ultrasound)• Relevant biochemical analysis"] OpinionNode["⚖️ Opinion Formulation
• Correlate injuries with history• Determine age and mechanism• Professional medical-legal assessment"] ReportNode["🖋️ Report Finalization and Signature
• Final review of documentation• Ensure full legal compliance• Formal signature and date"] StartNode --> HistoryNode HistoryNode --> ExamNode ExamNode --> InvestNode InvestNode --> OpinionNode OpinionNode --> ReportNode style StartNode fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style HistoryNode fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style ExamNode fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style InvestNode fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style OpinionNode fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style ReportNode fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD START["⚡ Glomerular Insult
• Initiating renal damage• Triggering pathology"] SITE{"🔍 Primary Site of Injury
• Target structure identification• Determines clinical phenotype"} POD["🧬 Podocyte Injury and Effacement
• Loss of filtration barrier• Disruption of slit diaphragms"] INF["🔥 Inflammatory Cell Infiltration
• Endothelial/mesangial focus• Neutrophil/macrophage recruitment"] NEPHROTIC["💧 Nephrotic Syndrome
• Massive proteinuria > 3.5 g/day• Edema and Hypoalbuminemia• Hyperlipidemia and Fatty casts"] NEPHRITIC["🩸 Nephritic Syndrome
• Hematuria and RBC Casts• Oliguria and Azotemia• Hypertension and Mild edema"] START --> SITE SITE --> POD SITE --> INF POD --> NEPHROTIC INF --> NEPHRITIC style START fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style SITE fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style POD fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style INF fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style NEPHROTIC fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A style NEPHRITIC fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00

flowchart TD Start["💊 Adrenergic Antagonists
• Block sympathomimetic effects• Classified by receptor affinity"] Alpha["⚡ Alpha-Blockers
• Target alpha-1 and alpha-2• Primary effect: Vasodilation"] Beta["🫀 Beta-Blockers
• Target beta-1 and beta-2• Decrease HR and Contractility"] Phenoxy["🧪 Phenoxybenzamine
• Irreversible non-selective• Used for Pheochromocytoma"] Osins["💧 Prazosin, -osins
• Selective alpha-1 blockers• Treat HTN and BPH symptoms"] Prop["📉 Propranolol
• Non-selective beta blocker• Risk: Bronchoconstriction"] Cardio["🛡️ Metoprolol, Atenolol
• Cardioselective (Beta-1)• Safer for asthma patients"] Start --> Alpha Start --> Beta Alpha --> Phenoxy Alpha --> Osins Beta --> Prop Beta --> Cardio style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Alpha fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Beta fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Phenoxy fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Osins fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Prop fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Cardio fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754

flowchart TD ANS["🧠 Autonomic Nervous System
• Regulates involuntary functions• Visceral motor system control• Maintains internal homeostasis"] SYM["🔥 Sympathetic Division
• Thoracolumbar Outflow (T1-L2)• Fight or Flight response activation• Short pre-ganglionic fibers"] PARA["🧊 Parasympathetic Division
• Craniosacral Outflow (CN, S2-S4)• Rest and Digest conservation• Long pre-ganglionic fibers"] ANS --> SYM ANS --> PARA style ANS fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SYM fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style PARA fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D

flowchart TD %% Epinephrine Alone Pathway EpiAlone["💉 Epinephrine Alone
• Non-selective agonist• Acts on alpha1, alpha2, beta1, beta2"] A1_VC["💢 Alpha1: Vasoconstriction
• Prominent pressor effect• Increased Systolic BP"] B2_VD["🌀 Beta2: Vasodilation
• Minor depressor effect• Skeletal muscle vessels"] NetHigh["📈 Net Effect: Increased MAP
• Alpha1 vasoconstriction dominates• High dose epi effect"] EpiAlone --> A1_VC EpiAlone --> B2_VD A1_VC --> NetHigh B2_VD --> NetHigh %% Epinephrine + Alpha-Blocker Pathway EpiAlpha["💊 Epinephrine + Alpha-Blocker
• e.g. Phentolamine/Phenoxybenzamine• Epinephrine Reversal phenomenon"] A1_Block["🚫 Alpha1: Blocked
• Alpha-receptor site occupied• Pressor effect inhibited"] B2_Unopposed["🔓 Beta2: Unopposed Vasodilation
• Beta2 activity remains active• Massive vessel relaxation"] NetLow["📉 Net Effect: Decreased MAP
• Hypotenstive response• Known as Dale Reversal"] EpiAlpha -- alpha-blocker --> A1_Block EpiAlpha --> B2_Unopposed A1_Block --> NetLow B2_Unopposed --> NetLow %% Styling style EpiAlone fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style A1_VC fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style B2_VD fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style NetHigh fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style EpiAlpha fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style A1_Block fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style B2_Unopposed fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style NetLow fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD PGC["🌱 Primordial Germ Cell
• Arise from yolk sac endoderm• Migrate to gonadal ridges• Diploid precursors"] MIT1{🔄 Mitosis
• Population expansion• Identical daughter cells} GONIUM["🧬 Gametogonium (2N, 2C)
• Spermatogonia or Oogonia• Stem cell renewal• Diploid status"] MIT2{🔄 Mitosis
• DNA replication S phase• Preparation for meiosis} PGAM["🧪 Primary Gametocyte (2N, 4C)
• Replicated DNA• Homologous pairing• Largest germ cell"] MEI1{✂️ Meiosis I
• Reductional division• Separation of homologs} SGAM["🔬 Secondary Gametocyte (1N, 2C)
• Haploid chromosome number• Decreased DNA content• Rapid transition phase"] MEI2{✂️ Meiosis II
• Equational division• Chromatid separation} GAM["🥚 Gamete (1N, 1C)
• Mature Sperm or Ovum• Final genetic blueprint• Ready for fertilization"] PGC --> MIT1 MIT1 --> GONIUM GONIUM --> MIT2 MIT2 --> PGAM PGAM --> MEI1 MEI1 --> SGAM SGAM --> MEI2 MEI2 --> GAM style PGC fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style MIT1 fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style GONIUM fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style MIT2 fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style PGAM fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style MEI1 fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style SGAM fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style MEI2 fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style GAM fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD SG["🧬 Spermatogonium 2n, 2d
• Undifferentiated germ cell• Found in basal compartment• Diploid state (46 chromosomes)"] PS["🌱 Primary Spermatocyte 2n, 4d
• Enters Meiosis I phase• DNA replication completed• Largest germ cell type"] SS["🌓 Secondary Spermatocyte 1n, 2d
• Result of Meiosis I• Haploid chromosome number• Short lifespan before Meiosis II"] ST["✨ Spermatid 1n, 1d
• Result of Meiosis II• Small, round immotile cell• Located near tubule lumen"] SZ["🏊 Spermatozoon 1n, 1d
• Mature motile sperm cell• Acrosome and tail formed• Final functional stage"] SG -- Mitosis --> PS PS -- Meiosis I --> SS SS -- Meiosis II --> ST ST -- Spermiogenesis --> SZ style SG fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style PS fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SS fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style ST fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style SZ fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD START["🏥 Acute Appendicitis
• Periumbilical to RLQ pain• Nausea, vomiting, anorexia• Tender McBurney point"] TYPE{"❓ Clinical Type?
• Determine via CT or US• Check for perforation/abscess"} UNCOMP["🟢 Uncomplicated
• Simple inflammation• No signs of rupture"] LAP["✂️ Laparoscopic Appendectomy
• Standard of surgical care• Minimally invasive approach"] POSTOP["💊 Post-op Abx <= 24h
• Short-course prophylaxis• Prevent surgical site infection"] COMP_ABS["🟡 Complicated (Abscess/Phlegmon)
• Contained perforation• Localized septic focus"] INITIAL["💉 Initial: IV Abx +/- Drainage
• Broad spectrum coverage• Percutaneous drain for abscess"] INTERVAL["⏳ Interval Appendectomy (6-8 wks)
• Delayed surgical removal• Minimizes risk of bowel injury"] COMP_FREE["🚨 Complicated (Free Perforation)
• Diffuse peritonitis signs• Hemodynamic instability risk"] URGENT["⚡ Urgent Appendectomy + IV Abx (3-7 days)
• Emergent surgical washout• Prolonged Abx for peritonitis"] START --> TYPE TYPE -- Uncomplicated --> UNCOMP UNCOMP --> LAP LAP --> POSTOP TYPE -- "Complicated (Abscess/Phlegmon)" --> COMP_ABS COMP_ABS --> INITIAL INITIAL --> INTERVAL TYPE -- "Complicated (Free Perforation)" --> COMP_FREE COMP_FREE --> URGENT style START fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style TYPE fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style UNCOMP fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style LAP fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style POSTOP fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style COMP_ABS fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style INITIAL fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style INTERVAL fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style COMP_FREE fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style URGENT fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD START["🚨 Hypertensive Emergency
• Severe HTN (usually >180/120)• Evidence of End-Organ Damage• Acute target organ dysfunction"] GOAL{"🎯 Management Goal
• Controlled reduction of BP• Prevent cerebral ischemia"} INITIAL["⏳ Initial Phase (First 8 hrs)
• Decrease MAP by <= 25 percent• Target within first few hours• Maintain perfusion pressure"] SUBSEQUENT["🗓️ Subsequent Phase
• Normalize BP over 24-48 hrs• Gradual reach of BP targets• Transition to oral agents"] ADMIN["💉 Administer IV Drugs
• Labetalol (alpha/beta blocker)• Nicardipine (Ca-channel blocker)• Titratable continuous infusions"] MONITOR["🩺 Monitor and Safety
• Avoid rapid BP drops• Watch for neuro/renal changes• Frequent BP checks (q5-15 min)"] START --> GOAL GOAL --> INITIAL INITIAL --> SUBSEQUENT SUBSEQUENT --> ADMIN ADMIN --> MONITOR style START fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style GOAL fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style INITIAL fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SUBSEQUENT fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style ADMIN fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style MONITOR fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845

flowchart TD Initial["🚨 Hypercalcemic Crisis
• Total Ca > 14 mg/dL• Altered mental status• Cardiac arrhythmias"] Step1["💧 Step 1: IV Hydration (NS)
• Restore intravascular volume• Normal Saline (0.9% NaCl)• Goal: 200-500 mL/hr"] Step2["💊 Step 2: Furosemide
• Give AFTER volume repletion• Inhibits Ca reabsorption• Prevents fluid overload"] Step3["🦴 Step 3: Bisphosphonates
• Inhibits osteoclasts• IV Zoledronic acid/Pamidronate• Delayed effect (2-4 days)"] Step4["⚡ Step 4: Calcitonin
• Rapid onset (4-6 hours)• Tachyphylaxis risk after 48h• Short-term bridge therapy"] Dialysis["🏥 Consider Dialysis
• For Severe/Refractory cases• Use low-calcium dialysate• Kidney failure management"] Initial --> Step1 Step1 --> Step2 Step2 --> Step3 Step3 --> Step4 Step4 -.-> |Severe/Refractory| Dialysis style Initial fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Step1 fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Step2 fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Step3 fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Step4 fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Dialysis fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845

flowchart TD A["🧬 Oogonium 2n
• Diploid stem cell• Undergoes mitosis in fetus"] B{"✂️ Meiosis I
• Reduction division• Homologous separation"} C["🥚 Primary Oocyte 2n
• Forms before birth• Enclosed in follicle"] D["⏸️ Prophase I
• Arrested at Dictyotene• Stays here until puberty"] E["🌙 Secondary Oocyte n
• Haploid cell (n)• First polar body released"] F["⏸️ Metaphase II
• Arrested after ovulation• Only completes if sperm enters"] G["👶 Ovum n + 2nd Polar Body
• Final mature gamete• Rapid Zygote formation"] A --> B B --> C C -- "Arrested in" --> D D -- "Puberty" --> E E -- "Arrested in" --> F F -- "Fertilization" --> G style A fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style B fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style C fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style D fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style E fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style F fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style G fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD subgraph M2["🧬 Meiosis II Error Pathway"] M2_Start["🧬 Parent Cell
• Diploid (2n) status• DNA replication complete"] M2_Step1["✅ Normal Meiosis I
• Homologous pairs separate• Leads to two haploid cells"] M2_Norm["😊 Normal Division
• Sister chromatids separate• Produces normal (n) gametes"] M2_NDJ{"⚠️ Nondisjunction
• Failure of chromatids to split• Occurs during Anaphase II"} M2_P1["➕ n+1 Gamete
• Extra sister chromatid• Leads to Trisomy after fertilization"] M2_M1["➖ n-1 Gamete
• Missing one chromosome• Leads to Monosomy after fertilization"] M2_Start --> M2_Step1 M2_Step1 --> M2_Norm M2_Step1 --> M2_NDJ M2_NDJ --> M2_P1 M2_NDJ --> M2_M1 end subgraph M1["🧬 Meiosis I Error Pathway"] M1_Start["🧬 Parent Cell
• Diploid (2n) precursor• Germ line cell entry"] M1_NDJ{"⚠️ Nondisjunction
• Homologous pairs fail to separate• Occurs during Anaphase I"} M1_P1["➕ n+1 Gametes
• 100 percent of gametes abnormal• Two n+1 and two n-1 formed"] M1_M1["➖ n-1 Gametes
• Lack of chromosomal pair• Risk increases with maternal age"] M1_Start --> M1_NDJ M1_NDJ --> M1_P1 M1_NDJ --> M1_M1 end style M2_Start fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style M2_Step1 fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#00251A style M2_Norm fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style M2_NDJ fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style M2_P1 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style M2_M1 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style M1_Start fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style M1_NDJ fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style M1_P1 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style M1_M1 fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD Zygote["🥚 Zygote
• Single cell fertilization product• Occurs in ampulla of fallopian tube• Totipotent genetic potential"] TwoCell["👥 2-Cell Stage
• First cleavage division• Occurs approx. 30 hours after fertilization• Blastomeres are equal in size"] FourCell["🍀 4-Cell Stage
• Second round of mitotic cleavage• Occurs approx. 40 to 50 hours post-fertilization• Zonal pellucida remains intact"] Morula["🍇 Morula (16-32 cells)
• Solid ball of blastomeres• Compaction process begins• Enters uterus 3 to 4 days after fertilization"] Zygote --> TwoCell TwoCell --> FourCell FourCell --> Morula style Zygote fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style TwoCell fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style FourCell fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Morula fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00

flowchart TD StartNode["🥚 Morula Enters Uterus
• Occurs 3-4 days post-fertilization• 16-32 cell stage 'mulberry'• Remains in uterine cavity 1-2 days"] FluidNode{"💧 Fluid Penetrates ZP
• Zona Pellucida becomes permeable• Uterine secretions enter morula• Na+/K+ ATPase activity increases"} BlastocoelNode["🌊 Blastocoel Forms
• Fluid-filled central cavity• Hydrostatic pressure increases• Transforms morula into blastocyst"] DiffNode["🧬 Blastocyst Differentiates
• Trophectoderm: Outer cell layer• Embryoblast: Inner cell mass (ICM)• Established embryonic polarity"] HatchNode["🐣 'Hatching'
• Zona Pellucida degenerates• Enzymatic lysis via proteases• Blastocyst expands and escapes"] ImplantNode["📍 Ready for Implantation
• Adhesion to endometrial epithelium• Occurs 6 days post-fertilization• Usually on posterior uterine wall"] StartNode --> FluidNode FluidNode --> BlastocoelNode BlastocoelNode --> DiffNode DiffNode --> HatchNode HatchNode --> ImplantNode style StartNode fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style FluidNode fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style BlastocoelNode fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style DiffNode fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style HatchNode fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style ImplantNode fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["🧬 ZP3 Binding
• Sperm binds to ZP3 glycoprotein• Occurs on the Zona Pellucida• Primary sperm receptor event"] AcrTrigger{"⚡ Acrosome Reaction
• Triggered by ZP3 binding• Exocytosis of acrosomal vesicle"} Enzymes["🧪 Enzyme Release
• Acrosin and proteases released• Essential for ZP penetration"] Digest["⛏️ Path Digestion
• Sperm digests path through ZP• Mechanical and chemical action"] Fusion["🤝 Membrane Fusion
• Sperm fuses with oocyte membrane• Membrane potential changes"] Cortical{"🛡️ Cortical Reaction
• Triggered by fusion event• Prevents multiple sperm entry"} CaInflux["🌊 Calcium Influx
• Ca2+ influx leads to release• Cortical granules exocytosed"] Hardening["🧱 Polyspermy Block
• Zona Pellucida hardens• Blocks additional sperm entry"] Meiosis["🔄 Meiotic Completion
• Oocyte completes Meiosis II• Second polar body extruded"] Pronuclei["🧬 Pronuclei Formation
• Male and female pronuclei form• Decondensation of chromatin"] Zygote["👶 Zygote Formation
• Pronuclear fusion occurs• Single cell diploid embryo"] Start --> AcrTrigger AcrTrigger --> Enzymes Enzymes --> Digest Digest --> Fusion Fusion --> Cortical Fusion --> Meiosis Cortical --> CaInflux CaInflux --> Hardening Meiosis --> Pronuclei Pronuclei --> Zygote style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style AcrTrigger fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Enzymes fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Digest fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Fusion fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Cortical fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style CaInflux fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Hardening fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style Meiosis fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Pronuclei fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Zygote fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["🎗️ Testicular Germ Cell Tumors
• Most common cancer in young men• Originates from germ cell precursors• Highly sensitive to chemotherapy"] Seminoma["🔬 Seminoma
• Slow-growing, radiosensitive• Normal AFP, maybe high beta-hCG• Fried egg histology (large cells)"] NonSeminoma["🧪 Non-Seminoma
• More aggressive clinical course• Frequently high AFP and beta-hCG• Mixed histologic patterns common"] Embryonal["🧫 Embryonal Carcinoma
• Painful, necrotic, hemorrhagic mass• Increased AFP and beta-hCG• Forms gland-like/tubular structures"] YolkSac["🍳 Yolk Sac Tumor
• Most common GCT in children• Schiller-Duval bodies on biopsy• Significantly high Marker AFP"] Chorio["🩸 Choriocarcinoma
• Early hematogenous metastasis• Extreme high levels of beta-hCG• Disordered trophoblastic tissue"] Teratoma["🦷 Teratoma
• Multiple germ layer tissues• Often chemoresistant in adults• Contains hair, bone, or cartilage"] %% Connections Start --> Seminoma Start --> NonSeminoma NonSeminoma --> Embryonal NonSeminoma --> YolkSac NonSeminoma --> Chorio NonSeminoma --> Teratoma %% Styling style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Seminoma fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style NonSeminoma fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Embryonal fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style YolkSac fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Chorio fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Teratoma fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845

flowchart TD EPI["🧫 Epiblast Cells
• Origin of all 3 germ layers• Derived from inner cell mass• Columnar epithelium layer"] INV{"🌀 Invagination at Primitive Streak
• Occurs during Gastrulation• Epithelial-mesenchymal transition• Controlled by FGF8 signaling"} REM["🧱 Remaining epiblast
• Cells that do not invaginate• Stay on dorsal surface"] W1["🌊 First wave displaces hypoblast
• Cells migrate ventrally• Replaces the original hypoblast"] W2["🥪 Second wave fills middle
• Cells stay between layers• Formation of loose connective tissue"] ENDO["🌱 Endoderm
• Forms GI tract lining• Forms respiratory system• Forms liver and pancreas"] MESO["💪 Mesoderm
• Forms muscles and bones• Forms circulatory system• Forms dermis of skin"] ECTO["🧠 Ectoderm
• Forms nervous system• Forms epidermis of skin• Forms sensory organs"] EPI --> INV EPI --> REM INV --> W1 INV --> W2 W1 --> ENDO W2 --> MESO REM --> ECTO style EPI fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style INV fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style REM fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style W1 fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style W2 fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style ENDO fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A style MESO fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A style ECTO fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD HF_Diag["🫀 Advanced HF Diagnosis
• NYHA Class III or IV• Severe structural disease• Frequent hospitalizations"] Refractory{"❓ Refractory Symptoms?
• Persistent dyspnea• Fatigue despite therapy• Low exercise tolerance"} Standard["📈 Standard HF Care
• GDMT optimization• Regular monitoring• Volumetric assessment"] PallConsult["🤝 Palliative Care Consult
• Interdisciplinary team• Holistic symptom review• Psychosocial support"] SymptomACP["📋 Symptoms & ACP
• Aggressive symptom control• Advance Care Planning• Goals of care defined"] Outcome["✨ Improved QoL
• Reduced caregiver burden• Patient-centered outcomes• Enhanced symptom relief"] HF_Diag --> Refractory Refractory -- "No" --> Standard Refractory -- "Yes" --> PallConsult PallConsult --> SymptomACP SymptomACP --> Outcome style HF_Diag fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style Refractory fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style Standard fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style PallConsult fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style SymptomACP fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style Outcome fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD subgraph UWI ["Uterine Wall Interaction"] APP["📍 Apposition
• Initial blastocyst positioning• Occurs in the implantation window• Pinopodes on endometrium emerge"] ADH["🔗 Adhesion
• Cytotrophoblast-endometrium link• Mediated by integrins and L-selectin• Stronger attachment to uterine wall"] INV["⚔️ Invasion
• Syncytiotrophoblast penetration• MMPs degrade extracellular matrix• Accessing maternal blood supply"] APP --> ADH ADH --> INV end style UWI fill:#F1F8E9,stroke:#333,stroke-width:2px style APP fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style ADH fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style INV fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000

flowchart TD MOR["🌑 Morula Stage
• 16-to-32 cell stage• Day 3-4 post-fertilization• Enclosed in Zona Pellucida"] COMP{🔄 Compaction
• Maximize cell-cell contact• Formation of tight junctions• Begins at 8-cell stage} BLAS["💧 Blastocyst Formation
• Cavitation process• Fluid-filled blastocoel forms• Sodium-potassium pump driven"] HATCH["🐣 Hatching
• From Zona Pellucida• Required for implantation• Day 5-6 post-fertilization"] DIFF{🧬 Differentiated Blastocyst
• First lineage specification• Polarity established} ICM["👶 Inner Cell Mass (Embryoblast)
• Pluripotent stem cells• Forms the embryo proper• Develops into ecto, endo, meso"] TROPH["🛡️ Trophoblast (Outer Layer)
• Becomes the placenta• Mediates implantation• Secretes hCG hormone"] MOR --> COMP COMP --> BLAS BLAS --> HATCH BLAS --> DIFF DIFF -- gives rise to --> ICM DIFF -- gives rise to --> TROPH style MOR fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style COMP fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style BLAS fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style HATCH fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style DIFF fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style ICM fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style TROPH fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00

flowchart TD N["🌱 Notochord
• Derived from mesoderm• Primary inducer of neurulation• Becomes nucleus pulposus"] IE["⚡ Induces Ectoderm
• Sonic hedgehog (SHH) signaling• Overlying ectoderm thickens• Specifies neuroectoderm fate"] NP["🧠 Neural Plate
• First sign of nervous system• Appears around day 18• Broad cranial/narrow caudal"] NGF["〰️ Neural Groove and Folds
• Invagination along midline• Neural folds rise laterally• Formation of neural groove"] NTCC["🧬 Neural Tube and Crest Cells
• Tube forms CNS (brain, spinal cord)• Crest forms PNS and ganglia• Closing begins in cervical region"] N --> IE IE --> NP NP --> NGF NGF --> NTCC style N fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style IE fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style NP fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style NGF fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style NTCC fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD START["🔍 Initial Screening
• High PSA or Abnormal DRE• Digital Rectal Exam findings• Age-adjusted PSA levels"] BIOPSY["💉 TRUS Biopsy
• Transrectal Ultrasound-Guided• Systematic core sampling• Local anesthesia required"] GLEASON{"📊 Gleason Score
• Primary + Secondary patterns• Grade Group 1 to 5• Histologic differentiation"} STAGE["🏁 Staging & Management
• TNM Staging completion• Active surveillance vs surgery• Radiation or Hormonal Tx"] START --> BIOPSY BIOPSY --> GLEASON GLEASON --> STAGE style START fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style BIOPSY fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style GLEASON fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style STAGE fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD Start["🦴 Notochord
• Derived from mesoderm• Defines longitudinal axis• Becomes Nucleus Pulposus"] Induce{"⚡ Ectoderm Induction
• Shh protein signaling• Paracrine interaction• Stimulates overlying tissue"} Plate["🧠 Neural Plate formation
• Thickening of ectoderm• Primary neurulation start• Neuroectoderm precursor"] Groove["🕳️ Neural Groove
• Central invagination• Bounded by neural folds• Rapid cell proliferation"] Fuse["🛡️ Neural Folds & Fusion
• Folds elevate and meet• Neural crest cells migrate• Midline closure occurs"] Tube["🧬 Neural Tube
• Final CNS precursor• Cranial/Caudal neuropores• Closes by end of week 4"] Start --> Induce Induce --> Plate Plate --> Groove Groove --> Fuse Fuse --> Tube style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Induce fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style Plate fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Groove fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Fuse fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Tube fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD Start["🥚 Blastocyst
• Implantation stage embryo• Inner cell mass (ICM)• Occurs around day 5 to 6"] Epiblast["🧬 Epiblast
• Derived from the ICM• Forms the embryo proper• Gives rise to all 3 layers"] PStreak["⚡ Primitive Streak
• Forms on dorsum of epiblast• Establishes body axes• Marks start of week 3"] Gastrulation["🔄 Gastrulation
• Cell migration via streak• Defines trilaminar disc• Transition to organogenesis"] Ectoderm["🧠 Ectoderm
• Forms Nervous System• Forms Epidermis/Skin• Neural tube development"] Mesoderm["💪 Mesoderm
• Muscle and Bone• Cardiovascular system• Urogenital structures"] Endoderm["🫁 Endoderm
• Lining of GI tract• Respiratory system epithelial• Glandular organs (Liver)"] Start --> Epiblast Epiblast --> PStreak PStreak --> Gastrulation Gastrulation --> Ectoderm Gastrulation --> Mesoderm Gastrulation --> Endoderm style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Epiblast fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style PStreak fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style Gastrulation fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style Ectoderm fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Mesoderm fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Endoderm fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754

flowchart TD NP["🧠 Neural Plate
• Derived from ectoderm• Induced by notochord• Thickened epithelium"] MHP["📐 Folding at MHP
• Median Hinge Point• Cells at midline wedge• Initiates neural groove"] NFE["⏫ Neural Folds Elevate
• Lateral edges rise up• Groove deepens• Forms bilateral ridges"] DLHP["↪️ Folding at DLHPs
• Dorsolateral Hinge Points• Folds curve inward• Brings edges together"] FAM["🔗 Fusion at Midline
• Adhesion of fold tips• Neural crest cells de-laminate• Surface ectoderm seals"] NT["🧬 Neural Tube
• Primordium of CNS• Closes cranially-caudally• Lumen forms ventricles"] NP --> MHP MHP --> NFE NFE --> DLHP DLHP --> FAM FAM --> NT style NP fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style MHP fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style NFE fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style DLHP fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style FAM fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style NT fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD StartNode["🌱 Somite
• Derived from paraxial mesoderm• Paired cuboidal structures• Formed along neural tube"] Sclerotome["🦴 Sclerotome
• Ventromedial portion• Forms vertebrae and ribs• Undergoes resegmentation"] Dermomyotome["🧬 Dermomyotome
• Dorsolateral portion• Precursor to skin and muscle• Splits into two distinct layers"] Dermatome["☁️ Dermatome
• Forms dermis of the back• Sensory nerve distribution• Contributes to subcutaneous tissue"] Myotome["💪 Myotome
• Forms skeletal muscle• Epaxial: Deep back muscles• Hypaxial: Body wall and limbs"] StartNode --> Sclerotome StartNode --> Dermomyotome Dermomyotome --> Dermatome Dermomyotome --> Myotome style StartNode fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style Sclerotome fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style Dermomyotome fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style Dermatome fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style Myotome fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000

flowchart TD PM["🧬 Paraxial Mesoderm
• Forms bilateral thick columns• Adjacent to neural tube• Develops into somites"] SM["🔲 Somites
• Segmented epithelial blocks• Forms from 3rd week• Organized craniocaudally"] SC["🦴 Sclerotome
• Ventromedial part of somite• Induced by Sonic Hedgehog• Mesenchymal transition"] DE["🧤 Dermatome
• Surface layer of dermomyotome• Contributes to skin layers• Sensory nerve supply source"] MY["💪 Myotome
• Deep layer of dermomyotome• Epaxial and hypaxial parts• Muscle precursor cells"] VR["🦴 Vertebrae and Ribs
• Axial skeleton foundation• Re-segmentation process• IV disc formation"] DB["🧴 Dermis of Back
• Connective tissue of skin• Covers dorsal body wall• Distinct from limb dermis"] SKM["🏃 Skeletal Muscle
• Body wall musculature• Limb bud migration• Multi-nucleated fibers"] PM --> SM SM --> SC SM --> DE SM --> MY SC --> VR DE --> DB MY --> SKM style PM fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SM fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style SC fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style DE fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style MY fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style VR fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style DB fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style SKM fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A

flowchart TD %% Main Header Node Start["🌱 Limb Bud Development
• Embryonic limb formation• Coordinated 3D patterning"] %% Process Nodes AER["📏 Apical Ectoderm Ridge (AER)
• Located at distal tip• Secretes FGFs• Crucial for outgrowth"] ZPA["🧭 Zone of Polarizing Activity (ZPA)
• Located at posterior base• Secretes SHH (Sonic Hedgehog)• Controls digit identity"] DV["🧬 Wnt7a and En1 Genes
• Wnt7a: Dorsal ectoderm• En1: Ventral ectoderm• Establishes 3rd axis"] %% Outcome Nodes PROX["📏 Proximo-distal Lengthening
• Growth from shoulder to finger• Mediated by FGFs"] ANT["🖐️ Antero-posterior Patterning
• Thumb to little finger axis• Mediated by SHH gradient"] AXIS["🦵 Dorso-ventral Axis
• Back of hand vs Palm side• Mediated by Wnt7a/En1"] %% Connections Start --> AER Start --> ZPA Start --> DV AER -- "FGFs" --> PROX ZPA -- "SHH" --> ANT DV -- "Signaling" --> AXIS %% Styling style Start fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style AER fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style ZPA fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style DV fill:#FFF8E1,stroke:#FFC107,stroke-width:2px,color:#5D3A00 style PROX fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style ANT fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style AXIS fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754

flowchart TD PM["🧬 Paraxial Mesoderm
• Forms alongside neural tube• Derived from gastrulation• Undergoes epithelialization"] SOM["🥚 Somite
• Cuboidal blocks of cells• Determines body segmentation• Appears in cranio-caudal sequence"] SCLE["🦴 Sclerotome
• Ventromedial portion• Forms vertebrae and ribs• Induced by Shh from notochord"] DERM["🛡️ Dermatome
• Dorsal-most layer• Forms dermis of the back• Retains segmental innervation"] MYO["💪 Myotome
• Intermediate layer• Forms skeletal muscle• Epaxial and hypaxial divisions"] PM --> SOM SOM --> SCLE SOM --> DERM SOM --> MYO style PM fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style SOM fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style SCLE fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style DERM fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style MYO fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD subgraph SpinalCord ["🧬 Spinal Cord Pathway"] N1["📍 1st Order Neuron
• Dorsal Root Ganglion• Sensory receptor input• Pain and temperature signals"] N2["📍 2nd Order Neuron
• Located in Posterior Horn• Rexed laminae I, II, V• Initial synapse point"] DEC["🔀 Decussation
• Ant. White Commissure• Crosses to opposite side• Spinal cord level segment"] ASC["🚀 Ascends Contralaterally
• Lateral Spinothalamic tract• Anterolateral system• Travels through brainstem"] end subgraph Brain ["🧠 Brain Pathway"] N3["📍 3rd Order Neuron
• VPL of Thalamus• Ventroposterolateral nucleus• Major sensory relay station"] CTX["🎭 Primary Somatosensory Cortex
• Postcentral Gyrus• BA 1, 2, and 3• Conscious perception"] end N1 --> N2 N2 --> DEC DEC --> ASC ASC --> N3 N3 --> CTX style SpinalCord fill:#F9F9F9,stroke:#333,stroke-dasharray: 5 5 style Brain fill:#F9F9F9,stroke:#333,stroke-dasharray: 5 5 style N1 fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style N2 fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style DEC fill:#FFEBEE,stroke:#F44336,stroke-width:2px,color:#5D0000 style ASC fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style N3 fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style CTX fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D

flowchart TD Start["🧪 Psoriasis Classic Agents
• Traditional topical therapies• Often used in combinaton• Cost-effective options"] CoalTar["🌑 Coal Tar
• Goeckerman Regimen• Combined with UV therapy• Anti-inflammatory effect"] SalAcid["💊 Salicylic Acid
• Keratolytic agent• Concentration: 2-10%• Enhances penetration"] Anthralin["✨ Anthralin (Dithranol)
• SCAT (Short Contact Therapy)• Ingram Regimen (with UVB)• Inhibits keratinocyte growth"] Start --> CoalTar Start --> SalAcid Start --> Anthralin style Start fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style CoalTar fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style SalAcid fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Anthralin fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00

flowchart TD StartNode["🌱 Metanephros
• Permanent kidney precursor• Appears in 5th week of gestation• Fully functional by week 10"] UB["🌿 Ureteric Bud
• Outgrowth of Mesonephric duct• Responsible for drainage anatomy"] MM["🧪 Metanephric Mesenchyme
• Also called Metanephric Blastema• Directs bud branching morphogenesis"] CS["📂 Collecting System
• Ureter and Renal Pelvis• Major and Minor Calyces• Collecting Ducts"] N["🔬 Nephron Formation
• Glomerulus and Bowman capsule• Proximal and Distal Tubules• Loop of Henle"] StartNode --> UB UB -- "Induces differentiation" --> MM MM -- "Induces branching" --> UB UB --> CS MM --> N style StartNode fill:#E8F5E9,stroke:#4CAF50,stroke-width:2px,color:#0D3E0D style UB fill:#E3F2FD,stroke:#2196F3,stroke-width:2px,color:#002754 style MM fill:#FFF3E0,stroke:#FF9800,stroke-width:2px,color:#5D2C00 style CS fill:#F3E5F5,stroke:#9C27B0,stroke-width:2px,color:#2A0845 style N fill:#E0F2F1,stroke:#009688,stroke-width:2px,color:#00251A

flowchart TD Start["🌱 Bipotential Gonad
• Undifferentiated stage• Present in early embryo• Can become male or female"] Testis["♂️ Testis
• SRY gene on Y chromosome• Medullary cords develop• Hormone production hub"] Ovary["♀️ Ovary
• Default pathway (no SRY)• Cortical cords develop• Follicle formation begins"] MullDegen["🚫 Mullerian Duct Degenerates
• Action of Sertoli cells• Mediated by AMH/MIS• Inhibits female structures"] WolfDevelop["📈 Wolffian Duct Develops
• Stimulated by Leydig cells• Driven by Testosterone• Forms epididymis/vas deferens"] MullDevelop["📈 Mullerian Duct Develops
• No AMH present• Paramesonephric duct growth• Forms uterus/tubes/vagina"] WolfDegen["🚫 Wolffian Duct Degenerates
• No Testosterone present• Mesonephric duct regresses• Male structures lost"] Start -- "SRY gene" --> Testis Start -- "No SRY" --> Ovary Testis -- "Sertoli cells: AMH" --> MullDegen Testis -- "Leydig cells: Testosterone" --> WolfDevelop Ovary -- "No AMH" --> MullDevelop Ovary -- "No Testosterone" --> WolfDegen style Start fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style Testis fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Ovary fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style MullDegen fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000 style WolfDevelop fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style MullDevelop fill:#E0F2F1, stroke:#009688, stroke-width:2px, color:#00251A style WolfDegen fill:#FFEBEE, stroke:#F44336, stroke-width:2px, color:#5D0000

flowchart TD Start["🧬 SYPHILIS SEROLOGY
• Comprehensive screening algo• T. pallidum identification• Differentiates active vs past infection"] Trad["📜 TRADITIONAL ALGO
• Starts with Nontreponemal test• Manual, low cost approach"] Rev["🔄 REVERSE ALGO
• Starts with Treponemal test• Automated high-volume labs"] TradNT["🧪 NONTREPONEMAL TEST
• Primary screen: RPR or VDRL• Detects cardiolipin antibodies"] RevTT["🧪 TREPONEMAL TEST
• Primary screen: EIA or CIA• Detects specific T. pallidum IgG"] TradNR["✅ SYPHILIS UNLIKELY
• Non-reactive RPR/VDRL• Re-test if high suspicion"] RevNR["✅ SYPHILIS UNLIKELY
• Non-reactive EIA/CIA• Re-test if high suspicion"] TradTT["🔬 TREPONEMAL TEST
• Confirmatory: TP-PA or FTA-ABS• Confirms positive screening test"] RevNT["🔬 NONTREPONEMAL TEST
• Confirmatory: RPR or VDRL• Helps determine treatment stage"] Start --> Trad Start --> Rev Trad --> TradNT TradNT -- Reactive --> TradTT TradNT -- Non-Reactive --> TradNR Rev --> RevTT RevTT -- Reactive --> RevNT RevTT -- Non-Reactive --> RevNR style Start fill:#E3F2FD, stroke:#2196F3, stroke-width:2px, color:#002754 style Trad fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style Rev fill:#FFF8E1, stroke:#FFC107, stroke-width:2px, color:#5D3A00 style TradNT fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style RevTT fill:#FFF3E0, stroke:#FF9800, stroke-width:2px, color:#5D2C00 style TradNR fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style RevNR fill:#E8F5E9, stroke:#4CAF50, stroke-width:2px, color:#0D3E0D style TradTT fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845 style RevNT fill:#F3E5F5, stroke:#9C27B0, stroke-width:2px, color:#2A0845