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Explain first 5 questions in detail with flowchart for mbbs exam

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MBBS Long Answer Questions - Detailed Answers

Q1. Structure and Functions of Mitochondria + Mitochondrial Disorders

Definition

Mitochondria are membrane-bound organelles called the "powerhouses of the cell" - they generate most of the cell's supply of ATP through oxidative phosphorylation.

Structure

Component	Description
Outer membrane	Smooth; contains porins (channel proteins) that regulate flow of ions and metabolites
Inner membrane	Folded into cristae - increases surface area; contains oxidative phosphorylation enzymes
Cristae	Shelf/tubule-like infoldings of inner membrane; site of ATP synthase (Complex V)
Matrix	Inner fluid compartment; contains enzymes for Krebs cycle, mtDNA, ribosomes
Outer chamber	Space between outer and inner membranes (intermembrane space)
Mitochondrial DNA (mtDNA)	37 genes; circular; maternally inherited; encodes 13 proteins for oxidative phosphorylation

Number: Fewer than 100 (adipocytes) up to several thousand (cardiomyocytes), depending on energy demand. Size: 0.5-10 micrometers; can be globular or elongated.

Structure Flowchart

MITOCHONDRION
       |
       ├── OUTER MEMBRANE
       │       └── Porins (channel proteins) → regulate ion/metabolite flow
       │
       ├── INTERMEMBRANE SPACE (Outer Chamber)
       │       └── Site of proton (H⁺) accumulation → drives ATP synthesis
       │
       ├── INNER MEMBRANE
       │       ├── Cristae (infoldings → ↑ surface area)
       │       ├── Electron Transport Chain (Complex I–IV)
       │       └── ATP Synthase (Complex V)
       │
       └── MATRIX
               ├── Krebs Cycle enzymes
               ├── Mitochondrial DNA (37 genes)
               ├── Mitochondrial ribosomes
               └── β-oxidation enzymes

Functions of Mitochondria

ATP production - via oxidative phosphorylation (main function)
Krebs cycle - acetyl-CoA → CO₂ + NADH + FADH₂
β-oxidation of fatty acids - generates acetyl-CoA
Apoptosis regulation - releases cytochrome c → activates caspase cascade
Calcium homeostasis - buffers cytoplasmic Ca²⁺
Heat generation - thermogenesis (brown adipose tissue)
Steroid hormone synthesis - cholesterol side-chain cleavage occurs in mitochondria
Urea cycle (partial) - carbamoyl phosphate synthetase I is in mitochondrial matrix
Self-replication - divide by binary fission

ATP Production Flowchart

Glucose / Fatty Acids / Amino Acids
              ↓
       GLYCOLYSIS (cytoplasm)
              ↓
         Pyruvate → Acetyl-CoA
              ↓
    KREBS CYCLE (matrix)
         → NADH, FADH₂, CO₂
              ↓
ELECTRON TRANSPORT CHAIN (inner membrane)
    Complex I (NADH dehydrogenase)
         ↓
    Complex II (succinate dehydrogenase)
         ↓
    Complex III (cytochrome bc1)
         ↓
    Complex IV (cytochrome c oxidase)
         ↓ (O₂ → H₂O)
    H⁺ pumped into intermembrane space
              ↓
    CHEMIOSMOSIS (H⁺ flows back through ATP synthase)
              ↓
           ATP SYNTHESIS
       (Net: ~30-32 ATP per glucose)

Common Mitochondrial Disorders & Clinical Features

Disorder	Defect	Key Clinical Features
MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes)	Complex I / mt-tRNA mutation (A3243G)	Stroke-like episodes <40 yrs, lactic acidosis, myopathy, seizures, dementia
MERRF (Myoclonic Epilepsy with Ragged Red Fibers)	mt-tRNA^Lys mutation	Myoclonus, epilepsy, cerebellar ataxia, ragged red fibers on Gomori trichrome stain
Leber's Hereditary Optic Neuropathy (LHON)	Complex I mutations (ND1, ND4, ND6 genes)	Bilateral painless central vision loss in young males; maternal inheritance
Kearns-Sayre Syndrome	Large mtDNA deletion	Ptosis, progressive external ophthalmoplegia, pigmentary retinopathy, cardiac conduction defects
Leigh Syndrome	Complex I, II, IV or pyruvate dehydrogenase deficiency	Infantile neurodegeneration, hypotonia, brainstem dysfunction, elevated lactate
Pearson Syndrome	mtDNA deletion	Sideroblastic anemia, exocrine pancreatic insufficiency

Mitochondrial Disorders Flowchart

Mitochondrial DNA Mutation
         |
    ┌────┴────────────────────┐
Maternal      Sporadic (large deletions)
inheritance        |
    |         Kearns-Sayre / Pearson
    |
    ├── Complex I defect → LHON / MELAS / Leigh
    ├── Complex II defect → Leigh syndrome
    ├── Complex IV defect → Leigh syndrome
    ├── mt-tRNA^Lys → MERRF
    └── mt-tRNA^Leu → MELAS

Common manifestations:
   → Muscle (myopathy, ragged red fibers)
   → Brain (encephalopathy, seizures, stroke)
   → Eye (ophthalmoplegia, optic neuropathy)
   → Heart (cardiomyopathy, conduction defects)
   → Metabolic (lactic acidosis, ↑ lactate:pyruvate)

Key point: Organs with highest energy demand (brain, muscle, heart, eye) are most affected.

Q2. Structure and Functions of Lysosomes + Lysosomal Storage Disorders

Definition

Lysosomes are membrane-bound organelles that serve as the "digestive system of the cell." They are produced by the Golgi apparatus and contain more than 60 hydrolytic enzymes that function optimally at pH 4.5-5.0 (maintained by H⁺-ATPase proton pump).

Structure

Component	Feature
Limiting membrane	Single phospholipid bilayer; contains H⁺-ATPase pump (maintains acidic pH)
Lumen pH	4.5-5.0 (acidic)
Hydrolytic enzymes	Proteases (cathepsins), lipases, nucleases, glycosidases, sulfatases, phosphatases
Size	0.1-1.2 µm
Shape	Spherical/oval
Marker enzyme	Acid phosphatase

Types:

Primary lysosomes - newly formed, contain enzymes but not yet actively digesting
Secondary lysosomes (phagolysosomes) - formed by fusion of primary lysosome with phagosome/endosome; active digestion occurs
Residual bodies - secondary lysosomes with undigested material (e.g., lipofuscin granules)
Autolysosomes - degrade the cell's own damaged organelles (autophagy)

Structure Flowchart

LYSOSOME BIOGENESIS
       |
   Rough ER
   (synthesizes hydrolytic enzymes as inactive precursors)
       ↓
   Mannose-6-phosphate (M6P) tag added
   in cis-Golgi
       ↓
   Sorted in trans-Golgi Network (TGN)
   via M6P receptors
       ↓
   Packaged into transport vesicles
       ↓
   Primary Lysosome
   (pH ~5.0; enzymes activated)
       ↓
   Fusion with:
   ┌────────────────────────────┐
   │                            │
Phagosome                  Autophagosome
(external material)       (cell's own organelles)
   ↓                            ↓
Phagolysosome              Autolysosome
   ↓
Enzymatic digestion → nutrients recycled
   ↓
Residual body (if undigested material remains)

Functions of Lysosomes

Intracellular digestion - breakdown of macromolecules (proteins, lipids, carbohydrates, nucleic acids)
Autophagy - recycling of damaged/aged organelles (mitochondria, ER) - quality control
Heterophagy - digestion of extracellular material taken in by endocytosis/phagocytosis
Immune defense - macrophages use lysosomes to destroy pathogens
Bone resorption - osteoclasts release lysosomal enzymes to degrade bone matrix
Regulation of apoptosis - "lysosomal membrane permeabilization" releases cathepsins
Fertilization - acrosome of sperm is a modified lysosome
Secretion - some cells secrete lysosomal contents (mast cells, cytotoxic T cells)

Lysosomal Storage Disorders (LSDs)

Mechanism: Deficiency of a specific lysosomal hydrolase → undigested substrate accumulates in lysosomes → cell dysfunction

Classification and Examples:

LYSOSOMAL STORAGE DISORDERS
            |
    ┌───────┼──────────────┬───────────────┐
Sphingolipidoses  Mucopolysaccharidoses  Glycogenoses  Mucolipidoses
(sphingolipid     (GAG accumulation)    (glycogen      
 accumulation)                          accumulation)
    |               |                    |
Gaucher's       Hurler's (MPS I)      Pompe disease
Niemann-Pick    Hunter's (MPS II)     (acid maltase
Fabry's         Sanfilippo (MPS III)   deficiency)
Krabbe's        Morquio (MPS IV)
Tay-Sachs       Maroteaux-Lamy (MPS VI)

Disorder	Deficient Enzyme	Accumulated Substrate	Key Features
Gaucher's (most common LSD)	Glucocerebrosidase	Glucocerebroside	Hepatosplenomegaly, bone pain, "Gaucher cells" (crinkled paper appearance)
Niemann-Pick (Type A/B)	Sphingomyelinase	Sphingomyelin	Hepatosplenomegaly, foam cells, cherry-red spot (Type A)
Tay-Sachs	Hexosaminidase A	GM2 ganglioside	Cherry-red spot, progressive neurodegeneration, no hepatosplenomegaly
Fabry's	α-Galactosidase A	Globotriaosylceramide	Skin angiokeratomas, renal failure, cardiomyopathy (X-linked)
Krabbe's	Galactocerebrosidase	Galactocerebroside	Infantile neurodegeneration, "globoid cells," peripheral neuropathy
Hurler's (MPS I)	α-L-Iduronidase	Heparan + dermatan sulfate	Coarse facies, corneal clouding, intellectual disability, gargoylism
Pompe's	Acid α-glucosidase	Glycogen	Hypertrophic cardiomyopathy, hypotonia, hepatomegaly ("floppy baby")

Treatment: Enzyme replacement therapy (ERT) is available for Gaucher's, Fabry's, Pompe's.

Q3. Fluid Mosaic Model of Biological Membranes (with Labelled Diagram)

Definition

The Fluid Mosaic Model was proposed by Singer and Nicolson in 1972. It describes the plasma membrane as a phospholipid bilayer in which proteins are embedded and float freely, like a mosaic of tiles in a fluid sea.

Components of the Plasma Membrane

1. Phospholipid Bilayer (the "fluid" part)

Two layers of phospholipids arranged tail-to-tail
Hydrophilic heads face the aqueous environments (ECF and ICF)
Hydrophobic tails face inward (create a hydrophobic core)
Membrane is fluid at body temperature (37°C); fluidity maintained by cholesterol

2. Membrane Proteins (the "mosaic" part)

Type	Description	Examples
Integral (Intrinsic) proteins	Span the entire bilayer (transmembrane proteins)	Ion channels, transporters, receptors
Peripheral (Extrinsic) proteins	Loosely attached to membrane surface	Cytoskeletal proteins, enzymes
Lipid-anchored proteins	Attached via lipid anchor in bilayer	G proteins, kinases

3. Cholesterol

Inserted between phospholipid tails
At body temperature: reduces fluidity (prevents excessive movement)
At low temperature: prevents membrane from becoming too rigid
Stabilizes membrane - acts as a "fluidity buffer"

4. Glycocalyx

Carbohydrate chains attached to glycoproteins and glycolipids on the outer surface
Functions: cell recognition, adhesion, immune response, protection

Labelled Diagram - Fluid Mosaic Model

        EXTRACELLULAR FLUID
                 |
    ┌────────────────────────────────────────────┐
    │  Glycoprotein   Glycolipid                 │
    │       ║              ║                     │
 ○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○  ← Hydrophilic heads
 ────────────────────────────────────────────────  (phosphate groups)
 ░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░░  ← Hydrophobic tails
 ░░░░  [Integral     ]  ░ [Choles-] ░░░░░░░░░░  (fatty acid chains)
 ░░░░  [Protein      ]  ░ [terol  ] ░░░░░░░░░░
 ○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○  ← Hydrophilic heads
    │      ║                  ║                 │
    │  Peripheral           Lipid-anchored      │
    │  Protein              Protein             │
    └────────────────────────────────────────────┘
        INTRACELLULAR FLUID (Cytoplasm)

Key: ○ = hydrophilic phosphate head
     ░ = hydrophobic fatty acid tail

Properties of the Fluid Mosaic Model

FLUID MOSAIC MODEL - KEY PROPERTIES

Fluidity
  ├── Proteins and lipids can move laterally (sideways)
  ├── Flip-flop (transverse movement) is rare
  ├── ↑ Unsaturated fatty acids → ↑ fluidity
  └── Cholesterol → stabilizes fluidity

Mosaic Pattern
  ├── Integral proteins (span entire bilayer)
  ├── Peripheral proteins (surface only)
  └── Lipid-anchored proteins

Asymmetry
  ├── Outer leaflet: phosphatidylcholine, sphingomyelin
  └── Inner leaflet: phosphatidylserine (flips outward in apoptosis),
                     phosphatidylethanolamine, phosphoinositides

Functions of Plasma Membrane

Function	How
Selective permeability	Controls entry/exit of substances
Cell signaling	Receptors recognize hormones/neurotransmitters
Cell adhesion	Adhesion molecules (integrins, cadherins)
Intercellular recognition	Glycocalyx - ABO blood groups, MHC antigens
Transport	Passive, active, vesicular
Electrochemical gradient	Na⁺/K⁺ pump maintains resting membrane potential

Q4. Membrane Transport Mechanisms

Overview

Every substance entering or leaving the cell must cross the plasma membrane. Transport mechanisms are classified by energy requirement and use of proteins.

Membrane transport: Simple diffusion (small/lipid-soluble molecules), carrier proteins, and channel proteins

Classification Flowchart

MEMBRANE TRANSPORT
         |
   ┌─────┴─────────────────────────────┐
PASSIVE (no energy)             ACTIVE (energy required)
(down concentration gradient)   (against concentration gradient)
   |                                   |
   ├── Simple Diffusion         ┌──────┴────────┐
   ├── Facilitated Diffusion  Primary Active   Secondary Active
   └── Osmosis                (ATP-driven)     (ion gradient-driven)
                              e.g., Na⁺/K⁺      e.g., SGLT1
                              ATPase            (Na⁺-glucose cotransport)
         |
   VESICULAR TRANSPORT
   ├── Endocytosis
   │     ├── Phagocytosis (large particles)
   │     ├── Pinocytosis (fluid/solutes)
   │     └── Receptor-mediated endocytosis (specific ligands)
   └── Exocytosis (secretion)

1. Simple (Passive) Diffusion

Definition: Movement of substances down their concentration gradient without energy and without transport proteins.

Substances that use it: Small, lipid-soluble, uncharged molecules

Gases: O₂, CO₂, N₂
Small uncharged: H₂O (also via aquaporins), ethanol, urea
Lipid-soluble: steroid hormones, fatty acids

Rate governed by Fick's Law:

Rate ∝ (Concentration gradient × Surface area × Membrane permeability)
        / Membrane thickness

2. Facilitated Diffusion (Passive + Protein-Mediated)

Definition: Movement down concentration gradient using a carrier or channel protein - no energy required.

Subtype	Mechanism	Examples
Carrier proteins	Bind molecule → conformational change → release on other side	GLUT1-4 (glucose transport), amino acid transporters
Channel proteins	Form hydrophilic pores; ion-selective	Na⁺, K⁺, Cl⁻, Ca²⁺ channels

Channel types:

Voltage-gated - open/close with changes in membrane potential (neurons)
Ligand-gated - open when neurotransmitter binds (acetylcholine receptor at NMJ)
Mechanically gated - open with physical deformation (inner ear hair cells)

3. Active Transport

Definition: Movement against concentration/electrochemical gradient; requires ATP or ion gradient.

Primary Active Transport

Directly uses ATP hydrolysis
Example: Na⁺/K⁺-ATPase pump
- Pumps 3 Na⁺ OUT, 2 K⁺ IN per ATP
- Maintains resting membrane potential
- Drives secondary active transport

Na⁺/K⁺-ATPase Mechanism:
  3 Na⁺ bind inside cell
         ↓
  ATP → ADP + Pi (phosphorylation)
         ↓
  Conformational change → 3 Na⁺ released OUTSIDE
         ↓
  2 K⁺ bind outside
         ↓
  Dephosphorylation → 2 K⁺ released INSIDE

Secondary Active Transport (Cotransport)

Uses the Na⁺ gradient (created by Na⁺/K⁺-ATPase) as the energy source
Symport: both molecules move in same direction
- SGLT1: Na⁺ + Glucose (intestine, kidney tubule)
- Na⁺-amino acid cotransporters
Antiport: molecules move in opposite directions
- Na⁺/H⁺ exchanger (NHE) - renal tubule
- Na⁺/Ca²⁺ exchanger (NCX) - cardiac muscle

4. Vesicular (Bulk) Transport

Endocytosis (into the cell)

Type	Particle Size	Example
Phagocytosis	Large (>0.5 µm)	Macrophage engulfs bacteria
Macropinocytosis	Large fluid droplets	Nutrient uptake
Receptor-mediated endocytosis (RME)	Specific ligands	LDL receptor (clathrin-coated pits), transferrin
Pinocytosis	Small fluid/solutes	Non-specific fluid uptake
Caveolae-mediated	Small	Albumin transport across endothelium

Receptor-Mediated Endocytosis:
Ligand binds receptor on cell surface
         ↓
Clathrin-coated pit forms
         ↓
Membrane invaginates → coated vesicle formed
         ↓
Clathrin coat shed → early endosome
         ↓
Acidification (pH ↓) → ligand-receptor dissociation
         ↓
┌────────────────────────────────┐
│                                │
Receptor recycled to         Ligand → lysosome
cell surface                 for degradation

Exocytosis (out of the cell)

Secretory vesicles fuse with plasma membrane → content released outside
Examples: Neurotransmitter release, insulin secretion, mucus secretion

Two Mechanisms in Detail

Mechanism 1: Na⁺/K⁺-ATPase (Primary Active Transport)

Ubiquitous in all animal cells
Uses 30% of cellular ATP
Generates electrochemical gradient essential for nerve impulse, muscle contraction, secondary active transport
Clinical: Cardiac glycosides (digoxin) inhibit Na⁺/K⁺-ATPase → ↑ intracellular Ca²⁺ → ↑ cardiac contractility

Mechanism 2: SGLT1 Cotransport (Secondary Active Transport)

Sodium-Glucose Linked Transporter 1
In intestinal epithelium: absorbs glucose from gut lumen
Na⁺ flows into cell down its gradient, dragging glucose with it
Clinical: SGLT2 inhibitors (dapagliflozin, empagliflozin) block glucose reabsorption in kidney → used for diabetes + heart failure

Q5. Carbohydrates - Definition, Classification, Glycosaminoglycans

Definition

Carbohydrates are polyhydroxy aldehydes or polyhydroxy ketones (or compounds that yield these on hydrolysis). They consist of carbon (C), hydrogen (H), and oxygen (O) in the general empirical formula (CH₂O)n.

Also called saccharides (Greek: sakcharon = sugar)
The name "carbohydrate" reflects "hydrates of carbon"

Classification Flowchart

CARBOHYDRATES
      |
      ├── MONOSACCHARIDES (cannot be hydrolyzed further)
      │       ├── Trioses (C3): Glyceraldehyde, DHAP
      │       ├── Tetroses (C4): Erythrose
      │       ├── Pentoses (C5): Ribose, Deoxyribose, Xylulose
      │       └── Hexoses (C6): Glucose, Fructose, Galactose, Mannose
      │               ├── Aldoses (aldehyde group): Glucose
      │               └── Ketoses (ketone group): Fructose
      │
      ├── DISACCHARIDES (2 monosaccharides)
      │       ├── Sucrose = Glucose + Fructose (table sugar)
      │       ├── Lactose = Glucose + Galactose (milk sugar)
      │       └── Maltose = Glucose + Glucose (malt sugar)
      │
      ├── OLIGOSACCHARIDES (3-10 monosaccharides)
      │       └── Examples: Raffinose, Stachyose
      │
      └── POLYSACCHARIDES (>10 monosaccharides)
              ├── HOMOPOLYSACCHARIDES (same monosaccharide units)
              │       ├── Starch (plant storage): Amylose + Amylopectin
              │       ├── Glycogen (animal storage): highly branched
              │       └── Cellulose (structural in plants)
              │
              └── HETEROPOLYSACCHARIDES (different monosaccharide units)
                      └── GLYCOSAMINOGLYCANS (GAGs) ← see below

Monosaccharides - Key Examples

Monosaccharide	Carbon	Type	Biological Role
Glucose	C6	Aldohexose	Primary energy fuel
Fructose	C6	Ketohexose	Fruit sugar; enters glycolysis
Galactose	C6	Aldohexose	Component of lactose; brain galactolipids
Ribose	C5	Aldopentose	Component of RNA, ATP, NAD⁺
Deoxyribose	C5	Aldopentose	Component of DNA
Glyceraldehyde	C3	Aldotriose	Glycolysis intermediate

Disaccharides - Key Examples

Disaccharide	Components	Bond	Found in
Sucrose	Glucose + Fructose	α1→β2	Sugar cane, plants
Lactose	Galactose + Glucose	β1→4	Milk (deficiency → lactose intolerance)
Maltose	Glucose + Glucose	α1→4	Starch digestion
Trehalose	Glucose + Glucose	α1→α1	Insects, fungi

Polysaccharides Comparison

Property	Starch	Glycogen	Cellulose
Monomer	Glucose	Glucose	Glucose
Bond	α-1,4 (straight) + α-1,6 (branches)	α-1,4 + α-1,6 (more branches)	β-1,4
Branching	Less branched	Highly branched	Linear
Location	Plants	Liver, muscle	Plant cell walls
Function	Energy storage	Energy storage	Structural

Glycosaminoglycans (GAGs) - Detailed Note

Definition

GAGs are long, unbranched heteropolysaccharides composed of repeating disaccharide units of:

An amino sugar (N-acetylglucosamine or N-acetylgalactosamine)
A uronic acid (glucuronic acid or iduronic acid) or galactose

They are highly negatively charged (due to sulfate groups and carboxyl groups) → attract water → form gel-like ground substance of ECM.

Classification of GAGs

GLYCOSAMINOGLYCANS (GAGs)
         |
    ┌────┴──────────────────────────────────────────┐
Non-sulfated GAGs               Sulfated GAGs
    |                                 |
Hyaluronic acid              ┌────────┼──────────────┐
(not covalently linked     Chondroitin   Dermatan    Keratan
 to protein)               sulfate       sulfate     sulfate
                                |
                           Heparan sulfate / Heparin

GAG	Repeating Unit	Sulfation	Location	Function
Hyaluronic acid	GlcA + GlcNAc	None	Synovial fluid, vitreous humor, cartilage	Lubrication, joint cushioning, wound healing
Chondroitin sulfate	GlcA + GalNAc-4-SO₄	Yes	Cartilage, tendon, bone	Structural integrity, compressive strength
Dermatan sulfate	IdoA + GalNAc-4-SO₄	Yes	Skin, blood vessels, heart valves	Wound healing, coagulation
Heparan sulfate	GlcA + GlcNAc	Yes	Cell surface, basement membrane	Cell signaling, growth factor binding
Heparin	IdoA-2-SO₄ + GlcNS	Heavily sulfated	Mast cell granules	Anticoagulant (binds antithrombin III)
Keratan sulfate	Gal + GlcNAc-6-SO₄	Yes	Cornea, cartilage	Corneal transparency

Proteoglycans

GAGs are usually linked covalently to core proteins → form proteoglycans (e.g., aggrecan, versican, perlecan)

PROTEOGLYCAN STRUCTURE:
    Core Protein
         |
    ├── GAG chain 1 (e.g., chondroitin sulfate)
    ├── GAG chain 2
    └── GAG chain 3

Proteoglycan + Hyaluronic acid backbone
→ Large aggregating complex (aggrecan)
→ Found in articular cartilage
→ Resists compressive forces in joints

Clinical Significance of GAGs

Condition	GAG involved	Mechanism
Osteoarthritis	↓ Chondroitin/Keratan sulfate	Loss of cartilage proteoglycans → joint degeneration
Mucopolysaccharidoses (MPS)	All types accumulate	Deficiency of lysosomal enzymes → GAG accumulation (Hurler, Hunter, Morquio, etc.)
Heparin therapy	Heparin (GAG)	Anticoagulant - binds antithrombin III → inhibits thrombin and factor Xa
Corneal clouding	↑ Keratan/dermatan sulfate	Seen in MPS (Hurler's, Scheie) → opacification
Premature aging syndromes	Altered hyaluronan metabolism	Impaired tissue hydration and repair

Summary Table

Question	Key Topic	Exam Keywords
Q1	Mitochondria	Cristae, mtDNA, MELAS, MERRF, LHON, Kearns-Sayre, ragged red fibers
Q2	Lysosomes	Acid hydrolases, M6P receptor, Gaucher's, Tay-Sachs, Hurler's, Pompe's
Q3	Fluid mosaic model	Singer & Nicolson 1972, phospholipid bilayer, integral/peripheral proteins, cholesterol
Q4	Membrane transport	Passive/active, Na⁺/K⁺-ATPase, SGLT, endocytosis, clathrin-coated pits
Q5	Carbohydrates	Monosaccharides, GAGs, hyaluronic acid, chondroitin, heparin, MPS disorders

*Sources: Guyton & Hall Textbook of Medical Physiology; Junqueira's Basic Histology; Histology: A Text and Atlas (Pawlina); Harper's Biochemistry (for GAG/lysosome content)*All 5 questions are covered in full detail. Here's a quick orientation guide to what you just received:

What's Covered

Q#	Topic	What's Included
Q1	Mitochondria	Structure diagram (textbook image), compartments table, ATP synthesis flowchart, 6 mitochondrial disorders with clinical features, disorder flowchart
Q2	Lysosomes	Biogenesis flowchart, types (primary/secondary/autolysosomes), 7 functions, full LSD classification tree, table of 7 major LSDs with enzymes/substrates/features
Q3	Fluid Mosaic Model	Singer & Nicolson 1972, all 4 components (phospholipids, proteins, cholesterol, glycocalyx), ASCII labelled diagram, asymmetry, 6 membrane functions
Q4	Membrane Transport	Full classification flowchart, simple diffusion + Fick's law, facilitated diffusion (carrier vs channel), primary active (Na⁺/K⁺-ATPase mechanism step-by-step), secondary active (SGLT1/NHE), vesicular transport (RME flowchart, exocytosis), clinical correlates
Q5	Carbohydrates	Definition, full classification flowchart, monosaccharide/disaccharide/polysaccharide tables, GAG structure + all 6 types with location/function, proteoglycan structure, clinical significance of GAGs

Exam tip: For each question, the flowcharts are the most efficient revision tool - memorize those first, then fill in details from the tables.

Create a quick reference PDF with all flowcharts and tables for revision

Reading File

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Running Command

ls /home/daytona/workspace/ 2>/dev/null || echo "workspace empty or not found"

Running Command

mkdir -p /home/daytona/workspace/mbbs-revision && python3 -c "import reportlab; print(reportlab.Version)"

Writing File

~/mbbs-revision/make_pdf.py

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import cm, mm
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_RIGHT
from reportlab.platypus import (SimpleDocTemplate, Paragraph, Spacer, Table,
                                 TableStyle, PageBreak, HRFlowable,
                                 KeepTogether)
from reportlab.platypus.flowables import Flowable
from reportlab.pdfgen import canvas
from reportlab.lib.colors import HexColor
import io

# ── Colour Palette ────────────────────────────────────────────────────────────
C_NAVY    = HexColor('#1a2e4a')
C_TEAL    = HexColor('#0f7b8c')
C_MINT    = HexColor('#e6f7f9')
C_GOLD    = HexColor('#f0a500')
C_AMBER   = HexColor('#fff3cd')
C_ORANGE  = HexColor('#e8700a')
C_ORANGE_LIGHT = HexColor('#fff8f0')
C_GREEN   = HexColor('#1e7e34')
C_GREEN_LIGHT  = HexColor('#e8f5e9')
C_RED     = HexColor('#c0392b')
C_RED_LIGHT    = HexColor('#fdecea')
C_PURPLE  = HexColor('#6a1b9a')
C_PURPLE_LIGHT = HexColor('#f3e5f5')
C_GREY    = HexColor('#455a64')
C_LGREY   = HexColor('#eceff1')
C_WHITE   = colors.white
C_BLACK   = colors.black

# ── Page setup ────────────────────────────────────────────────────────────────
PAGE_W, PAGE_H = A4
MARGIN = 1.8*cm
CONTENT_W = PAGE_W - 2*MARGIN

def add_page_decorations(canvas_obj, doc):
    """Header/footer on every page."""
    canvas_obj.saveState()
    # Top bar
    canvas_obj.setFillColor(C_NAVY)
    canvas_obj.rect(0, PAGE_H-1.1*cm, PAGE_W, 1.1*cm, fill=1, stroke=0)
    canvas_obj.setFillColor(C_WHITE)
    canvas_obj.setFont('Helvetica-Bold', 9)
    canvas_obj.drawString(MARGIN, PAGE_H-0.72*cm, 'MBBS QUICK REFERENCE  |  Cell Biology & Biochemistry')
    canvas_obj.setFont('Helvetica', 8)
    canvas_obj.drawRightString(PAGE_W-MARGIN, PAGE_H-0.72*cm, 'For Revision Only')
    # Bottom bar
    canvas_obj.setFillColor(C_NAVY)
    canvas_obj.rect(0, 0, PAGE_W, 0.8*cm, fill=1, stroke=0)
    canvas_obj.setFillColor(C_WHITE)
    canvas_obj.setFont('Helvetica', 8)
    canvas_obj.drawCentredString(PAGE_W/2, 0.27*cm, f'Page {doc.page}')
    # Accent line under header
    canvas_obj.setStrokeColor(C_GOLD)
    canvas_obj.setLineWidth(2)
    canvas_obj.line(0, PAGE_H-1.1*cm, PAGE_W, PAGE_H-1.1*cm)
    canvas_obj.restoreState()

# ── Styles ────────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def S(name, **kw):
    return ParagraphStyle(name, **kw)

sTitle = S('sTitle', fontSize=26, textColor=C_WHITE, fontName='Helvetica-Bold',
           leading=32, alignment=TA_CENTER)
sSubtitle = S('sSubtitle', fontSize=13, textColor=C_AMBER, fontName='Helvetica',
              leading=18, alignment=TA_CENTER)
sQHead = S('sQHead', fontSize=15, textColor=C_WHITE, fontName='Helvetica-Bold',
           leading=20, alignment=TA_LEFT, spaceAfter=2)
sSecHead = S('sSecHead', fontSize=11, textColor=C_NAVY, fontName='Helvetica-Bold',
             leading=15, spaceBefore=8, spaceAfter=3)
sMiniHead = S('sMiniHead', fontSize=9.5, textColor=C_TEAL, fontName='Helvetica-Bold',
              leading=13, spaceBefore=5, spaceAfter=2)
sBody = S('sBody', fontSize=8.5, textColor=C_BLACK, fontName='Helvetica',
          leading=13, spaceAfter=3)
sBold = S('sBold', fontSize=8.5, textColor=C_BLACK, fontName='Helvetica-Bold',
          leading=13)
sBox  = S('sBox', fontSize=8, textColor=C_NAVY, fontName='Helvetica',
          leading=12, leftIndent=4, rightIndent=4)
sCell = S('sCell', fontSize=8, textColor=C_BLACK, fontName='Helvetica', leading=11)
sCellB= S('sCellB', fontSize=8, textColor=C_NAVY, fontName='Helvetica-Bold', leading=11)
sCellW= S('sCellW', fontSize=8.5, textColor=C_WHITE, fontName='Helvetica-Bold', leading=12)
sFlow = S('sFlow', fontSize=8, textColor=C_NAVY, fontName='Courier', leading=11,
          backColor=HexColor('#f0f4f8'), leftIndent=6)
sNote = S('sNote', fontSize=7.5, textColor=C_GREY, fontName='Helvetica-Oblique', leading=11)
sKeyword = S('sKeyword', fontSize=8, textColor=C_RED, fontName='Helvetica-Bold', leading=11)

# ── Helper Flowables ──────────────────────────────────────────────────────────
def qbanner(q_num, title, color=C_TEAL):
    data = [[Paragraph(f'Q{q_num}', sCellW),
             Paragraph(title, sCellW)]]
    t = Table(data, colWidths=[1.3*cm, CONTENT_W-1.3*cm])
    t.setStyle(TableStyle([
        ('BACKGROUND', (0,0), (-1,-1), color),
        ('TEXTCOLOR',  (0,0), (-1,-1), C_WHITE),
        ('ALIGN', (0,0),(0,0), 'CENTER'),
        ('VALIGN', (0,0),(-1,-1), 'MIDDLE'),
        ('LEFTPADDING', (0,0),(-1,-1), 8),
        ('RIGHTPADDING',(0,0),(-1,-1), 8),
        ('TOPPADDING',  (0,0),(-1,-1), 8),
        ('BOTTOMPADDING',(0,0),(-1,-1), 8),
        ('ROWBACKGROUNDS',(0,0),(-1,-1),[color]),
    ]))
    return t

def section_head(text):
    return Paragraph(text, sSecHead)

def mini_head(text):
    return Paragraph(text, sMiniHead)

def body(text):
    return Paragraph(text, sBody)

def note(text):
    return Paragraph(f'<i>{text}</i>', sNote)

def sp(h=0.2):
    return Spacer(1, h*cm)

def hr(color=C_TEAL, thickness=0.5):
    return HRFlowable(width='100%', thickness=thickness, color=color, spaceAfter=4, spaceBefore=4)

def flowbox(lines):
    """Render a monospaced flowchart block."""
    joined = '\n'.join(lines)
    data = [[Paragraph(joined.replace('\n','<br/>'), sFlow)]]
    t = Table(data, colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ('BACKGROUND',(0,0),(-1,-1), HexColor('#f0f4f8')),
        ('BOX',(0,0),(-1,-1),0.8, C_TEAL),
        ('LEFTPADDING',(0,0),(-1,-1),8),
        ('RIGHTPADDING',(0,0),(-1,-1),8),
        ('TOPPADDING',(0,0),(-1,-1),6),
        ('BOTTOMPADDING',(0,0),(-1,-1),6),
    ]))
    return t

def make_table(headers, rows, col_widths=None, hdr_color=C_NAVY, zebra=True):
    if col_widths is None:
        col_widths = [CONTENT_W/len(headers)]*len(headers)
    header_row = [Paragraph(h, sCellW) for h in headers]
    data = [header_row]
    for i, row in enumerate(rows):
        bg = HexColor('#f7fbfc') if (zebra and i%2==0) else C_WHITE
        data.append([Paragraph(str(c), sCell) for c in row])
    t = Table(data, colWidths=col_widths, repeatRows=1)
    style = [
        ('BACKGROUND',(0,0),(-1,0), hdr_color),
        ('TEXTCOLOR',(0,0),(-1,0), C_WHITE),
        ('FONTNAME',(0,0),(-1,0),'Helvetica-Bold'),
        ('FONTSIZE',(0,0),(-1,-1), 8),
        ('GRID',(0,0),(-1,-1),0.4, HexColor('#b0bec5')),
        ('ROWBACKGROUNDS',(0,1),(-1,-1),[HexColor('#f7fbfc'), C_WHITE]),
        ('VALIGN',(0,0),(-1,-1),'TOP'),
        ('LEFTPADDING',(0,0),(-1,-1),5),
        ('RIGHTPADDING',(0,0),(-1,-1),5),
        ('TOPPADDING',(0,0),(-1,-1),4),
        ('BOTTOMPADDING',(0,0),(-1,-1),4),
    ]
    t.setStyle(TableStyle(style))
    return t

def highlight_box(text, bg=C_AMBER, border=C_GOLD):
    data = [[Paragraph(text, sBox)]]
    t = Table(data, colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ('BACKGROUND',(0,0),(-1,-1), bg),
        ('BOX',(0,0),(-1,-1),1, border),
        ('LEFTPADDING',(0,0),(-1,-1),8),
        ('RIGHTPADDING',(0,0),(-1,-1),8),
        ('TOPPADDING',(0,0),(-1,-1),5),
        ('BOTTOMPADDING',(0,0),(-1,-1),5),
    ]))
    return t

def two_col(left_items, right_items):
    """Two-column layout using a table."""
    half = (CONTENT_W - 0.4*cm) / 2
    rows = []
    max_len = max(len(left_items), len(right_items))
    left_items  += [''] * (max_len - len(left_items))
    right_items += [''] * (max_len - len(right_items))
    for l, r in zip(left_items, right_items):
        rows.append([l, r])
    t = Table(rows, colWidths=[half, half], hAlign='LEFT')
    t.setStyle(TableStyle([
        ('VALIGN',(0,0),(-1,-1),'TOP'),
        ('LEFTPADDING',(0,0),(-1,-1),0),
        ('RIGHTPADDING',(0,0),(-1,-1),4),
        ('TOPPADDING',(0,0),(-1,-1),0),
        ('BOTTOMPADDING',(0,0),(-1,-1),0),
    ]))
    return t

# ══════════════════════════════════════════════════════════════════════════════
# CONTENT BUILDER
# ══════════════════════════════════════════════════════════════════════════════
story = []

# ── COVER PAGE ────────────────────────────────────────────────────────────────
def cover_page():
    # Big coloured banner
    cover_data = [[
        Paragraph('MBBS QUICK REFERENCE', sTitle),
    ]]
    cover_t = Table(cover_data, colWidths=[CONTENT_W])
    cover_t.setStyle(TableStyle([
        ('BACKGROUND',(0,0),(-1,-1), C_NAVY),
        ('TOPPADDING',(0,0),(-1,-1), 30),
        ('BOTTOMPADDING',(0,0),(-1,-1), 20),
    ]))
    story.append(cover_t)
    story.append(sp(0.3))

    sub_data = [[Paragraph('Cell Biology &amp; Biochemistry', sSubtitle)]]
    sub_t = Table(sub_data, colWidths=[CONTENT_W])
    sub_t.setStyle(TableStyle([
        ('BACKGROUND',(0,0),(-1,-1), C_TEAL),
        ('TOPPADDING',(0,0),(-1,-1), 12),
        ('BOTTOMPADDING',(0,0),(-1,-1), 12),
    ]))
    story.append(sub_t)
    story.append(sp(1.2))

    # Questions covered
    toc_rows = [
        ['Q1', 'Mitochondria', 'Structure · Functions · Disorders (MELAS, MERRF, LHON, KSS, Leigh)'],
        ['Q2', 'Lysosomes',    'Structure · Functions · Lysosomal Storage Disorders'],
        ['Q3', 'Fluid Mosaic Model', 'Membrane structure · Components · Properties'],
        ['Q4', 'Membrane Transport', 'Passive · Active · Vesicular · Clinical correlates'],
        ['Q5', 'Carbohydrates', 'Classification · Polysaccharides · GAGs · MPS disorders'],
    ]
    story.append(section_head('Topics Covered'))
    story.append(make_table(
        ['Q#', 'Topic', 'Subtopics'],
        toc_rows,
        col_widths=[1.2*cm, 4*cm, CONTENT_W-5.2*cm],
        hdr_color=C_NAVY
    ))
    story.append(sp(0.8))
    story.append(highlight_box(
        '⚡  Exam Tip: Each section has a FLOWCHART (grey box) + TABLE. '
        'Study the flowcharts first for the big picture, then the tables for detail.',
        bg=C_AMBER, border=C_GOLD
    ))
    story.append(PageBreak())

cover_page()

# ══════════════════════════════════════════════════════════════════════════════
# Q1 — MITOCHONDRIA
# ══════════════════════════════════════════════════════════════════════════════
story.append(qbanner(1, 'Mitochondria — Structure, Functions &amp; Disorders', C_NAVY))
story.append(sp(0.3))

story.append(section_head('Structure at a Glance'))
story.append(make_table(
    ['Component', 'Description', 'Key Role'],
    [
        ['Outer membrane',  'Smooth; contains porins (channel proteins)',       'Regulates ion/metabolite flow'],
        ['Intermembrane space', 'Between outer and inner membranes',            'H⁺ accumulation → drives ATP synthesis'],
        ['Inner membrane',  'Folded into cristae; houses ETC + ATP synthase',   'Site of oxidative phosphorylation'],
        ['Cristae',         'Infoldings of inner membrane → ↑ surface area',    'Attachment of ETC complexes I–V'],
        ['Matrix',          'Gel-like interior',                                 'Krebs cycle, β-oxidation, mtDNA, ribosomes'],
        ['mtDNA',           '37 genes; circular; maternally inherited',          'Encodes 13 ETC proteins + rRNA/tRNA'],
    ],
    col_widths=[3.5*cm, 7*cm, CONTENT_W-10.5*cm],
    hdr_color=C_TEAL
))
story.append(sp(0.3))

story.append(section_head('Structure Flowchart'))
story.append(flowbox([
    'MITOCHONDRION',
    '   |',
    '   ├── OUTER MEMBRANE ── Porins → regulate ion/metabolite entry',
    '   |',
    '   ├── INTERMEMBRANE SPACE (Outer Chamber)',
    '   |       └── H⁺ pumped here → proton gradient → ATP synthesis',
    '   |',
    '   ├── INNER MEMBRANE',
    '   |       ├── Cristae (infoldings → ↑↑ surface area)',
    '   |       ├── ETC: Complex I → II → III → IV (electrons flow)',
    '   |       └── ATP Synthase (Complex V) ← H⁺ flows back through',
    '   |',
    '   └── MATRIX',
    '           ├── Krebs Cycle enzymes',
    '           ├── β-Oxidation of fatty acids',
    '           ├── Mitochondrial DNA (37 genes)',
    '           └── Mitochondrial ribosomes (55S)',
]))
story.append(sp(0.3))

story.append(section_head('ATP Synthesis Flowchart'))
story.append(flowbox([
    'Glucose / Fatty Acids / Amino Acids',
    '       ↓',
    'GLYCOLYSIS (cytoplasm) → Pyruvate → Acetyl-CoA',
    '       ↓',
    'KREBS CYCLE (matrix) → NADH + FADH₂ + CO₂',
    '       ↓',
    'ELECTRON TRANSPORT CHAIN (inner membrane cristae)',
    '  Complex I (NADH dehydrogenase)  → pumps 4H⁺',
    '  Complex II (succinate DH)       → no H⁺ pumping',
    '  Complex III (cytochrome bc1)    → pumps 4H⁺',
    '  Complex IV (cytochrome c oxidase) → pumps 2H⁺ + O₂ → H₂O',
    '       ↓',
    'H⁺ GRADIENT (intermembrane space)',
    '       ↓',
    'ATP SYNTHASE (Complex V) — CHEMIOSMOSIS',
    '  H⁺ flows back into matrix → rotary motor → ATP synthesis',
    '       ↓',
    'NET YIELD: ~30–32 ATP per glucose molecule',
]))
story.append(sp(0.3))

story.append(section_head('Functions of Mitochondria'))
story.append(make_table(
    ['Function', 'Detail'],
    [
        ['ATP production',          'Oxidative phosphorylation; main energy currency of cell'],
        ['Krebs (TCA) cycle',       'Acetyl-CoA oxidation → NADH, FADH₂, CO₂'],
        ['β-oxidation',             'Fatty acid breakdown → Acetyl-CoA'],
        ['Apoptosis regulation',    'Cytochrome c release → caspase cascade activation'],
        ['Ca²⁺ homeostasis',        'Buffers cytoplasmic calcium; modulates signaling'],
        ['Thermogenesis',           'Uncoupling protein (UCP1) in brown fat → heat generation'],
        ['Steroid synthesis (partial)', 'Cholesterol side-chain cleavage in matrix'],
        ['Urea cycle (partial)',    'Carbamoyl phosphate synthetase I in matrix'],
        ['Self-replication',        'Binary fission; controlled by mtDNA'],
    ],
    col_widths=[5*cm, CONTENT_W-5*cm],
    hdr_color=C_TEAL
))
story.append(sp(0.3))

story.append(section_head('Mitochondrial Disorders'))
story.append(flowbox([
    'mtDNA MUTATION',
    '      |',
    '      ├── Maternal inheritance (point mutations)',
    '      |       ├── mt-tRNAᴸᵉᵘ mutation → MELAS',
    '      |       ├── mt-tRNAᴸʸˢ mutation → MERRF',
    '      |       └── Complex I gene (ND1/ND4/ND6) → LHON',
    '      |',
    '      └── Sporadic large deletions',
    '              ├── Kearns-Sayre Syndrome',
    '              ├── Pearson Syndrome',
    '              └── Progressive External Ophthalmoplegia (PEO)',
    '',
    'ORGANS MOST AFFECTED (highest energy demand):',
    '  Brain → Muscle → Heart → Eyes → Kidney',
]))
story.append(sp(0.3))

story.append(make_table(
    ['Disorder', 'Mutation / Defect', 'Key Clinical Features'],
    [
        ['MELAS',            'mt-tRNAᴸᵉᵘ (A3243G); Complex I',  'Stroke-like episodes <40 yrs, lactic acidosis, myopathy, seizures'],
        ['MERRF',            'mt-tRNAᴸʸˢ (A8344G)',              'Myoclonus, epilepsy, cerebellar ataxia, ragged-red fibers'],
        ['LHON',             'Complex I genes (ND1, ND4, ND6)',   'Bilateral painless central vision loss; young males; maternal inheritance'],
        ['Kearns-Sayre',     'Large mtDNA deletion',              'Ptosis, ophthalmoplegia, pigmentary retinopathy, cardiac block'],
        ['Leigh Syndrome',   'Complex I/II/IV or PDH deficiency', 'Infantile neurodegeneration, hypotonia, brainstem dysfunction, ↑ lactate'],
        ['Pearson Syndrome', 'mtDNA deletion',                    'Sideroblastic anaemia, exocrine pancreatic insufficiency'],
    ],
    col_widths=[3.5*cm, 5.5*cm, CONTENT_W-9*cm],
    hdr_color=C_RED
))
story.append(sp(0.2))
story.append(highlight_box(
    '🔑 Key words: Ragged-red fibers (MERRF/MELAS on Gomori trichrome) | '
    'Maternal inheritance | Lactic acidosis | "Heteroplasmy" = mixture of normal + mutant mtDNA',
    bg=C_RED_LIGHT, border=C_RED
))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# Q2 — LYSOSOMES
# ══════════════════════════════════════════════════════════════════════════════
story.append(qbanner(2, 'Lysosomes — Structure, Functions &amp; Storage Disorders', C_PURPLE))
story.append(sp(0.3))

story.append(section_head('Structure'))
story.append(make_table(
    ['Feature', 'Detail'],
    [
        ['Membrane',        'Single phospholipid bilayer; contains H⁺-ATPase (maintains acidic pH)'],
        ['pH',              '4.5–5.0 (acidic) — optimal for hydrolytic enzymes'],
        ['Marker enzyme',   'Acid phosphatase'],
        ['Size',            '0.1–1.2 µm; spherical/oval'],
        ['Enzymes (>60)',   'Proteases (cathepsins), lipases, nucleases, glycosidases, sulfatases, phosphatases'],
    ],
    col_widths=[4*cm, CONTENT_W-4*cm],
    hdr_color=C_PURPLE
))
story.append(sp(0.3))

story.append(section_head('Types of Lysosomes'))
story.append(make_table(
    ['Type', 'Description'],
    [
        ['Primary lysosome',      'Newly formed; contains enzymes; not yet actively digesting'],
        ['Secondary lysosome',    'Formed by fusion of primary lysosome + phagosome/endosome; active digestion'],
        ['Autolysosome',          'Fuses with autophagosome → degrades cell\'s own damaged organelles (autophagy)'],
        ['Residual body',         'Secondary lysosome with undigested material (e.g., lipofuscin granules in aged cells)'],
    ],
    col_widths=[4*cm, CONTENT_W-4*cm],
    hdr_color=C_PURPLE
))
story.append(sp(0.3))

story.append(section_head('Lysosome Biogenesis Flowchart'))
story.append(flowbox([
    'Rough ER → synthesises hydrolytic enzymes (inactive precursors)',
    '       ↓',
    'Mannose-6-phosphate (M6P) tag added in cis-Golgi',
    '       ↓',
    'Sorted in trans-Golgi Network (TGN) via M6P receptors',
    '       ↓',
    'Packaged into clathrin-coated vesicles',
    '       ↓',
    'Primary Lysosome (pH ≈5.0; enzymes activated)',
    '       ↓',
    'Fuses with:',
    '  ┌──────────────────────┬───────────────────────┐',
    '  Phagosome              Endosome                Autophagosome',
    '  (bacteria/debris)      (endocytosed material)  (old organelles)',
    '       ↓                       ↓                      ↓',
    '  Phagolysosome          Late endosome          Autolysosome',
    '       ↓                       ↓                      ↓',
    '       └─────── Enzymatic digestion → Nutrients recycled ──────┘',
    '                                   ↓',
    '                           Residual body (if undigested residue)',
]))
story.append(sp(0.3))

story.append(section_head('Functions'))
story.append(make_table(
    ['Function', 'Detail'],
    [
        ['Intracellular digestion',  'Breakdown of proteins, lipids, carbs, nucleic acids'],
        ['Autophagy',                'Recycling of damaged organelles; cellular quality control'],
        ['Heterophagy (phagocytosis)', 'Macrophage destruction of pathogens'],
        ['Bone resorption',          'Osteoclasts release lysosomal enzymes to degrade bone matrix (H⁺ + cathepsin K)'],
        ['Apoptosis regulation',     'Lysosomal membrane permeabilisation → cathepsin B/D release'],
        ['Fertilisation',            'Acrosome of sperm = specialised lysosome (releases acrosin)'],
        ['Secretion',                'Mast cells (histamine), cytotoxic T cells (perforin/granzyme)'],
    ],
    col_widths=[5*cm, CONTENT_W-5*cm],
    hdr_color=C_PURPLE
))
story.append(sp(0.3))

story.append(section_head('Lysosomal Storage Disorders (LSDs) — Classification'))
story.append(flowbox([
    'LYSOSOMAL STORAGE DISORDERS',
    '            |',
    '   ┌────────┼────────────────┬──────────────┐',
    'Sphingolipidoses  Mucopolysaccharidoses  Glycogenoses  Mucolipidoses',
    '(sphingolipid     (GAG accumulation)    (glycogen',
    ' accumulation)         |                  accumulation)',
    '      |          MPS I  Hurler\'s              |',
    ' Gaucher\'s       MPS II Hunter\'s         Pompe disease',
    ' Niemann-Pick    MPS III Sanfilippo       (acid maltase↓)',
    ' Fabry\'s         MPS IV  Morquio',
    ' Krabbe\'s        MPS VI  Maroteaux-Lamy',
    ' Tay-Sachs',
]))
story.append(sp(0.3))

story.append(make_table(
    ['Disorder', 'Deficient Enzyme', 'Substrate', 'Key Features'],
    [
        ['Gaucher\'s (most common)', 'Glucocerebrosidase',     'Glucocerebroside',     'Hepatosplenomegaly, bone pain, Gaucher cells (crinkled paper)'],
        ['Niemann-Pick A/B',       'Sphingomyelinase',        'Sphingomyelin',        'HSM, foam cells, cherry-red spot (Type A)'],
        ['Tay-Sachs',              'Hexosaminidase A',        'GM₂ ganglioside',      'Cherry-red spot, progressive neurodegeneration, no HSM'],
        ['Fabry\'s',               'α-Galactosidase A',       'Globotriaosylceramide','Angiokeratomas, renal failure, cardiomyopathy (X-linked)'],
        ['Krabbe\'s',              'Galactocerebrosidase',    'Galactocerebroside',   'Infantile neurodegeneration, globoid cells, neuropathy'],
        ['Hurler\'s (MPS I)',      'α-L-Iduronidase',         'Heparan + Dermatan SO₄','Coarse facies, corneal clouding, intellectual disability'],
        ['Pompe\'s',               'Acid α-glucosidase',      'Glycogen',             'Hypertrophic CM, hypotonia, hepatomegaly (floppy baby)'],
    ],
    col_widths=[3.8*cm, 4*cm, 3.5*cm, CONTENT_W-11.3*cm],
    hdr_color=C_PURPLE
))
story.append(sp(0.2))
story.append(highlight_box(
    '🔑 Key words: M6P receptor | Acid phosphatase (marker) | Heterophagy vs Autophagy | '
    'ERT available for Gaucher\'s, Fabry\'s, Pompe\'s | Cherry-red spot = Tay-Sachs + Niemann-Pick A',
    bg=C_PURPLE_LIGHT, border=C_PURPLE
))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# Q3 — FLUID MOSAIC MODEL
# ══════════════════════════════════════════════════════════════════════════════
story.append(qbanner(3, 'Fluid Mosaic Model of Biological Membranes', C_GREEN))
story.append(sp(0.3))

story.append(section_head('Definition'))
story.append(body(
    'Proposed by <b>Singer and Nicolson (1972)</b>. Describes the plasma membrane as a '
    '<b>phospholipid bilayer</b> in which proteins are embedded and can move freely — '
    'like a mosaic of tiles floating in a fluid sea.'
))
story.append(sp(0.3))

story.append(section_head('Components'))
story.append(make_table(
    ['Component', 'Structure', 'Function'],
    [
        ['Phospholipid bilayer',    'Amphipathic molecules; hydrophilic heads face aqueous environment; hydrophobic tails face inward',  'Selective barrier; basis of membrane structure'],
        ['Integral (Intrinsic) proteins', 'Span entire bilayer (transmembrane); multiple hydrophobic α-helices', 'Ion channels, transporters, receptors, enzymes'],
        ['Peripheral (Extrinsic) proteins', 'Loosely attached to surface by ionic/H-bonds', 'Cytoskeletal anchors, signal transduction'],
        ['Lipid-anchored proteins', 'Attached via covalent lipid anchor (GPI, myristoyl)', 'G-proteins, kinases, cell signaling'],
        ['Cholesterol',            'Intercalated between phospholipid tails',              'Stabilises fluidity (prevents extremes of fluidity/rigidity)'],
        ['Glycocalyx',             'Carbohydrate chains on glycoproteins and glycolipids (outer surface only)', 'Cell recognition, ABO antigens, adhesion, protection'],
    ],
    col_widths=[4*cm, 6.5*cm, CONTENT_W-10.5*cm],
    hdr_color=C_GREEN
))
story.append(sp(0.3))

story.append(section_head('Fluid Mosaic Model — Labelled Diagram'))
story.append(flowbox([
    '              EXTRACELLULAR FLUID',
    '                       |',
    ' Glycoprotein      Glycolipid          Peripheral protein',
    '      ║                ║                       |',
    ' ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●  ← Hydrophilic heads (phosphate)',
    ' ──────────────────────────────────────────────',
    ' ░░░░░░  [Integral protein]  ░ [Cholesterol] ░  ← Hydrophobic tails (fatty acids)',
    ' ░░░░░░  [spans bilayer   ]  ░░░░░░░░░░░░░░░░░',
    ' ──────────────────────────────────────────────',
    ' ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●  ← Hydrophilic heads',
    '        |                  |',
    '  GPI-anchored protein  Lipid-anchored protein',
    '                       |',
    '              INTRACELLULAR FLUID (Cytoplasm)',
    '',
    'KEY:  ● = hydrophilic phosphate head    ░ = hydrophobic fatty acid tail',
]))
story.append(sp(0.3))

story.append(section_head('Key Properties'))
story.append(flowbox([
    'FLUIDITY',
    '  ├── Proteins + lipids move laterally (sideways) → FLUID',
    '  ├── Flip-flop (transverse movement) is RARE (requires flippase enzyme)',
    '  ├── ↑ Unsaturated fatty acids (kinked tails) → ↑ fluidity',
    '  ├── ↑ Temperature → ↑ fluidity',
    '  └── Cholesterol → moderates fluidity (buffer at both extremes)',
    '',
    'ASYMMETRY (two leaflets differ)',
    '  ├── Outer leaflet: Phosphatidylcholine, sphingomyelin, glycolipids',
    '  └── Inner leaflet: Phosphatidylserine (flips out → apoptosis signal),',
    '                      Phosphatidylethanolamine, Phosphoinositides (PIP₂, PIP₃)',
    '',
    'SELECTIVE PERMEABILITY',
    '  ├── Freely permeable: O₂, CO₂, H₂O, small uncharged lipids',
    '  ├── Impermeable: ions, large polar molecules, charged molecules',
    '  └── Require transport proteins: glucose, amino acids, ions',
]))
story.append(sp(0.3))

story.append(section_head('Functions of Plasma Membrane'))
story.append(make_table(
    ['Function', 'Mechanism'],
    [
        ['Selective permeability',   'Controls entry/exit of all substances'],
        ['Cell signaling',           'Receptors (GPCRs, RTKs) recognise hormones/neurotransmitters'],
        ['Cell adhesion',            'Integrins, cadherins, selectins'],
        ['Cell recognition',         'Glycocalyx — ABO blood groups, MHC antigens, immune recognition'],
        ['Transport',                'Passive, active, and vesicular transport mechanisms'],
        ['Electrochemical gradient', 'Na⁺/K⁺ pump maintains resting membrane potential (−70 mV)'],
    ],
    col_widths=[5*cm, CONTENT_W-5*cm],
    hdr_color=C_GREEN
))
story.append(sp(0.2))
story.append(highlight_box(
    '🔑 Key words: Singer and Nicolson 1972 | Amphipathic phospholipids | Integral vs Peripheral proteins | '
    'Cholesterol = fluidity buffer | Glycocalyx = ABO/MHC | Phosphatidylserine flip = apoptosis marker',
    bg=C_GREEN_LIGHT, border=C_GREEN
))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# Q4 — MEMBRANE TRANSPORT
# ══════════════════════════════════════════════════════════════════════════════
story.append(qbanner(4, 'Membrane Transport Mechanisms', C_ORANGE))
story.append(sp(0.3))

story.append(section_head('Classification Flowchart'))
story.append(flowbox([
    'MEMBRANE TRANSPORT',
    '         |',
    '   ┌─────┴──────────────────────────────────────────┐',
    'PASSIVE (no energy)                       ACTIVE (energy required)',
    '(↓ concentration gradient)                (↑ against gradient)',
    '   |                                              |',
    '   ├── 1. Simple Diffusion             ┌──────────┴────────────┐',
    '   |      (no protein)           Primary Active          Secondary Active',
    '   |                             (ATP-driven)             (ion gradient)',
    '   ├── 2. Facilitated Diffusion        |                       |',
    '   |      ├── Carrier proteins    Na⁺/K⁺-ATPase          Symport:  SGLT1',
    '   |      └── Channel proteins    H⁺-ATPase              Antiport: Na⁺/H⁺',
    '   |                              Ca²⁺-ATPase',
    '   └── 3. Osmosis',
    '',
    'VESICULAR TRANSPORT',
    '   ├── Endocytosis:',
    '   |     ├── Phagocytosis (particles >0.5 µm)',
    '   |     ├── Pinocytosis (fluid/solutes)',
    '   |     └── Receptor-mediated endocytosis (specific ligands, clathrin-coated)',
    '   └── Exocytosis (secretion)',
]))
story.append(sp(0.3))

story.append(section_head('1. Simple Diffusion'))
story.append(make_table(
    ['Aspect', 'Detail'],
    [
        ['Definition',   'Movement DOWN concentration gradient; no energy; no proteins'],
        ['Substances',   'O₂, CO₂, N₂, ethanol, urea, steroid hormones, small uncharged lipids'],
        ['Fick\'s Law',  'Rate ∝ (Conc. gradient × Area × Permeability) / Membrane thickness'],
    ],
    col_widths=[3.5*cm, CONTENT_W-3.5*cm],
    hdr_color=C_ORANGE
))
story.append(sp(0.3))

story.append(section_head('2. Facilitated Diffusion (Passive + Protein-Mediated)'))
story.append(make_table(
    ['Protein Type', 'Mechanism', 'Examples', 'Regulation'],
    [
        ['Carrier proteins', 'Bind molecule → conformational change → release on other side', 'GLUT1-4 (glucose), amino acid transporters', 'Saturable; substrate-specific'],
        ['Channel proteins (voltage-gated)', 'Open/close with membrane potential change', 'Na⁺, K⁺ channels in neurons', 'Depolarisation opens channel'],
        ['Channel proteins (ligand-gated)', 'Open when neurotransmitter binds', 'nAChR at NMJ (acetylcholine)', 'Ligand binding'],
        ['Channel proteins (mechanically-gated)', 'Open with physical deformation', 'Hair cells of inner ear', 'Mechanical stretch'],
    ],
    col_widths=[3.5*cm, 4.5*cm, 4*cm, CONTENT_W-12*cm],
    hdr_color=C_ORANGE
))
story.append(sp(0.3))

story.append(section_head('3. Active Transport'))
story.append(flowbox([
    'PRIMARY ACTIVE TRANSPORT — Na⁺/K⁺-ATPase',
    '',
    '  3 Na⁺ bind INSIDE cell',
    '         ↓',
    '  ATP → ADP + Pᵢ (phosphorylation of pump)',
    '         ↓',
    '  Conformational change → 3 Na⁺ released OUTSIDE',
    '         ↓',
    '  2 K⁺ bind OUTSIDE',
    '         ↓',
    '  Dephosphorylation → 2 K⁺ released INSIDE',
    '         ↓',
    '  Net: 3 Na⁺ OUT, 2 K⁺ IN (electrogenic → net -1 charge inside)',
    '',
    'SECONDARY ACTIVE TRANSPORT — uses Na⁺ gradient from Na⁺/K⁺-ATPase',
    '',
    '  SYMPORT (same direction):',
    '  Na⁺ (↓ gradient) + Glucose → SGLT1 → both enter cell (intestine/kidney)',
    '',
    '  ANTIPORT (opposite direction):',
    '  Na⁺ IN + H⁺ OUT via NHE (Na⁺/H⁺ exchanger) → acid-base regulation',
]))
story.append(sp(0.3))

story.append(section_head('4. Receptor-Mediated Endocytosis (RME) Flowchart'))
story.append(flowbox([
    'Ligand binds specific receptor on cell surface',
    '         ↓',
    'Receptor-ligand complex migrates to clathrin-coated pit',
    '         ↓',
    'Membrane invaginates → clathrin-coated vesicle pinches off (dynamin-dependent)',
    '         ↓',
    'Clathrin coat shed → early endosome formed',
    '         ↓',
    'Acidification (H⁺-ATPase) → pH drops → ligand-receptor dissociation',
    '         ↓',
    '  ┌──────────────────────────────────────────────┐',
    'Receptor recycled                       Ligand → late endosome',
    'to cell surface                                  ↓',
    '(e.g., LDL receptor)                   Lysosome fusion → degradation',
    '',
    'Example: LDL receptor pathway → cholesterol uptake',
    '         Defect → Familial Hypercholesterolaemia',
]))
story.append(sp(0.3))

story.append(section_head('Clinical Correlates'))
story.append(make_table(
    ['Mechanism', 'Drug/Condition', 'Clinical Significance'],
    [
        ['Na⁺/K⁺-ATPase inhibition', 'Digoxin (cardiac glycoside)', '↑ intracellular Na⁺ → ↑ Ca²⁺ via NCX → ↑ cardiac contractility (used in heart failure/AF)'],
        ['SGLT2 inhibition (kidney)', 'Dapagliflozin, Empagliflozin', 'Block glucose reabsorption → glucosuria → ↓ blood glucose (T2DM + heart failure treatment)'],
        ['RME defect',               'Familial Hypercholesterolaemia', 'LDL receptor mutation → LDL not internalised → ↑↑ plasma cholesterol → premature atherosclerosis'],
        ['Aquaporin channels',       'Diabetes insipidus',             'ADH stimulates AQP2 insertion in collecting duct; defect → inability to concentrate urine'],
    ],
    col_widths=[4*cm, 4.5*cm, CONTENT_W-8.5*cm],
    hdr_color=C_ORANGE
))
story.append(sp(0.2))
story.append(highlight_box(
    '🔑 Key words: Na⁺/K⁺-ATPase = 3 Na⁺ out, 2 K⁺ in, 1 ATP | SGLT1 (intestine/kidney) vs SGLT2 (kidney only) | '
    'Clathrin-coated pits = RME | Pinocytosis = cell drinking | Phagocytosis = cell eating',
    bg=C_ORANGE_LIGHT, border=C_ORANGE
))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# Q5 — CARBOHYDRATES
# ══════════════════════════════════════════════════════════════════════════════
story.append(qbanner(5, 'Carbohydrates — Definition, Classification &amp; Glycosaminoglycans', C_TEAL))
story.append(sp(0.3))

story.append(section_head('Definition'))
story.append(body(
    'Carbohydrates are <b>polyhydroxy aldehydes or polyhydroxy ketones</b>, or compounds '
    'that yield these on hydrolysis. General empirical formula: <b>(CH₂O)n</b>. '
    'Also called <b>saccharides</b>. Composed of C, H, and O.'
))
story.append(sp(0.3))

story.append(section_head('Classification Flowchart'))
story.append(flowbox([
    'CARBOHYDRATES',
    '      |',
    '      ├── MONOSACCHARIDES (cannot be hydrolysed further)',
    '      |       ├── Trioses (C3): Glyceraldehyde (aldose), DHAP (ketose)',
    '      |       ├── Pentoses (C5): Ribose (RNA), Deoxyribose (DNA), Xylulose',
    '      |       └── Hexoses (C6):',
    '      |               ├── Aldoses: Glucose, Galactose, Mannose',
    '      |               └── Ketoses: Fructose',
    '      |',
    '      ├── DISACCHARIDES (2 monosaccharides linked by glycosidic bond)',
    '      |       ├── Sucrose  = Glucose + Fructose   (α1→β2; plants)',
    '      |       ├── Lactose  = Galactose + Glucose  (β1→4; milk)',
    '      |       └── Maltose  = Glucose + Glucose    (α1→4; starch digest)',
    '      |',
    '      ├── OLIGOSACCHARIDES (3–10 units): Raffinose, Stachyose',
    '      |',
    '      └── POLYSACCHARIDES (>10 units)',
    '              ├── HOMOPOLYSACCHARIDES (same monomer)',
    '              |       ├── Starch: Amylose (α1→4) + Amylopectin (α1→4 + α1→6)',
    '              |       ├── Glycogen: α1→4 + α1→6 (highly branched; liver/muscle)',
    '              |       └── Cellulose: β1→4 (structural; plants; indigestible)',
    '              |',
    '              └── HETEROPOLYSACCHARIDES (different monomers)',
    '                      └── GLYCOSAMINOGLYCANS (GAGs) ← see below',
]))
story.append(sp(0.3))

story.append(section_head('Key Monosaccharides'))
story.append(make_table(
    ['Monosaccharide', 'Carbons', 'Type', 'Biological Role'],
    [
        ['Glucose',     'C6', 'Aldohexose', 'Primary energy fuel; blood sugar; substrate for glycolysis'],
        ['Fructose',    'C6', 'Ketohexose', 'Fruit sugar; enters glycolysis at fructose-6-P or DHAP'],
        ['Galactose',   'C6', 'Aldohexose', 'Component of lactose; brain galactolipids; converted to glucose-1-P'],
        ['Ribose',      'C5', 'Aldopentose', 'Component of RNA, ATP, NAD⁺, FAD, CoA'],
        ['Deoxyribose', 'C5', 'Aldopentose', 'Component of DNA backbone'],
        ['Glyceraldehyde','C3','Aldotriose', 'Glycolysis intermediate; simplest monosaccharide'],
    ],
    col_widths=[3.5*cm, 2*cm, 3*cm, CONTENT_W-8.5*cm],
    hdr_color=C_TEAL
))
story.append(sp(0.3))

story.append(section_head('Polysaccharides Comparison'))
story.append(make_table(
    ['Property', 'Starch', 'Glycogen', 'Cellulose'],
    [
        ['Monomer',    'Glucose', 'Glucose', 'Glucose'],
        ['Bond',       'α-1,4 + α-1,6', 'α-1,4 + α-1,6', 'β-1,4'],
        ['Branching',  'Less branched', 'Highly branched (every 8–12 glucose)', 'Linear; no branching'],
        ['Location',   'Plants (potato, rice, wheat)', 'Liver + Muscle (animals)', 'Plant cell walls'],
        ['Function',   'Energy storage (plants)', 'Energy storage (animals)', 'Structural support'],
        ['Digestibility', 'Digestible (amylase)', 'Digestible', 'NOT digestible (no β-glucosidase in humans)'],
    ],
    col_widths=[3.5*cm, 4*cm, 5*cm, CONTENT_W-12.5*cm],
    hdr_color=C_TEAL
))
story.append(sp(0.3))

story.append(section_head('Glycosaminoglycans (GAGs) — Detailed Note'))
story.append(body(
    'GAGs are <b>long, unbranched heteropolysaccharides</b> of repeating disaccharide units consisting of '
    'an <b>amino sugar</b> (GlcNAc or GalNAc) + a <b>uronic acid</b> (GlcA or IdoA) or galactose. '
    'Highly negatively charged (sulfate + carboxyl groups) → attract water → form gel-like ECM ground substance.'
))
story.append(sp(0.2))

story.append(section_head('GAG Classification Flowchart'))
story.append(flowbox([
    'GLYCOSAMINOGLYCANS (GAGs)',
    '         |',
    '    ┌────┴─────────────────────────────────────────────────┐',
    'Non-sulfated                              Sulfated GAGs',
    '    |                            ┌────────┬────────────────┼────────────┐',
    'Hyaluronic acid         Chondroitin-SO₄  Dermatan-SO₄  Keratan-SO₄  Heparan-SO₄/Heparin',
    '(NOT protein-bound)          |                                           |',
    '(no protein core)     Most abundant GAG                         Most sulfated = Heparin',
    '                      in cartilage',
]))
story.append(sp(0.3))

story.append(make_table(
    ['GAG', 'Amino Sugar', 'Uronic Acid', 'Location', 'Function'],
    [
        ['Hyaluronic acid',    'GlcNAc',  'GlcA',       'Synovial fluid, vitreous humor, cartilage, skin', 'Lubrication, shock absorption, wound healing'],
        ['Chondroitin-SO₄',   'GalNAc',  'GlcA',       'Cartilage, tendon, bone, aorta',                  'Structural integrity, compressive strength'],
        ['Dermatan-SO₄',      'GalNAc',  'IdoA',       'Skin, heart valves, blood vessels',               'Wound healing, coagulation, anticoagulation'],
        ['Heparan-SO₄',       'GlcNAc',  'GlcA/IdoA',  'Cell surfaces, basement membranes',               'Growth factor binding, cell adhesion, angiogenesis'],
        ['Heparin',           'GlcNS',   'IdoA-2-SO₄', 'Mast cell granules',                              'Anticoagulant: binds antithrombin III → inhibits thrombin + Xa'],
        ['Keratan-SO₄',       'GlcNAc',  'Galactose',  'Cornea, cartilage, intervertebral disc',          'Corneal transparency, cartilage structure'],
    ],
    col_widths=[3.5*cm, 2.5*cm, 3*cm, 4.5*cm, CONTENT_W-13.5*cm],
    hdr_color=C_TEAL
))
story.append(sp(0.3))

story.append(section_head('Proteoglycans'))
story.append(flowbox([
    'GAG chains attached covalently to CORE PROTEIN → PROTEOGLYCAN',
    '',
    '  Core Protein',
    '       ├── GAG chain 1 (chondroitin sulfate)',
    '       ├── GAG chain 2',
    '       └── GAG chain 3',
    '',
    '  Proteoglycan + Hyaluronic acid backbone → AGGRECAN aggregate',
    '  → Found in articular cartilage → resists compressive forces',
    '',
    'Examples:',
    '  Aggrecan    → cartilage (chondroitin-SO₄ + keratan-SO₄)',
    '  Perlecan    → basement membrane (heparan-SO₄)',
    '  Versican    → skin, blood vessels',
    '  Syndecan    → cell surface heparan-SO₄ proteoglycan',
]))
story.append(sp(0.3))

story.append(section_head('Clinical Significance of GAGs'))
story.append(make_table(
    ['Condition', 'GAG Involved', 'Mechanism / Relevance'],
    [
        ['Osteoarthritis',        'Chondroitin, Keratan SO₄', '↓ proteoglycan in cartilage → loss of compressive strength → joint degeneration'],
        ['Mucopolysaccharidoses', 'All GAG types',            'Deficiency of lysosomal GAG-degrading enzymes → GAG accumulation (Hurler, Hunter, Morquio, Sanfilippo, etc.)'],
        ['Heparin therapy',       'Heparin',                  'Binds antithrombin III → inhibits thrombin (IIa) + Factor Xa → anticoagulation (DVT/PE treatment)'],
        ['Corneal clouding',      'Keratan, Dermatan SO₄',    'GAG accumulation in corneal stroma → opacification (seen in Hurler\'s, Morquio)'],
        ['Marfan syndrome',       'Altered ECM proteoglycans', 'FBN1 mutation → disrupted ECM → aortic dilation, lens dislocation'],
    ],
    col_widths=[3.5*cm, 4*cm, CONTENT_W-7.5*cm],
    hdr_color=C_TEAL
))
story.append(sp(0.2))
story.append(highlight_box(
    '🔑 Key words: (CH₂O)n formula | Reducing vs non-reducing sugars | Sucrose = non-reducing | '
    'Lactose intolerance = lactase deficiency | GAGs = negatively charged | Heparin = most sulfated GAG | '
    'Hyaluronic acid = only GAG not linked to protein | M6P = lysosomal targeting signal',
    bg=C_MINT, border=C_TEAL
))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# SUMMARY / RAPID REVIEW PAGE
# ══════════════════════════════════════════════════════════════════════════════
story.append(qbanner(0, 'RAPID REVIEW — One-Page Summary', C_NAVY))
story.append(sp(0.4))

story.append(make_table(
    ['Q#', 'Topic', 'Must-Know Keywords', 'Classic Exam Trap'],
    [
        ['Q1', 'Mitochondria',
         'Powerhouse; cristae; mtDNA 37 genes; maternal inheritance; Complex I–V; ATP synthase',
         'MELAS vs MERRF: MELAS = stroke-like episodes; MERRF = myoclonus + ragged-red fibers'],
        ['Q2', 'Lysosomes',
         'Acid phosphatase; M6P receptor; pH 4.5–5; autophagy vs heterophagy; ERT for Gaucher/Fabry/Pompe',
         'Tay-Sachs = NO hepatosplenomegaly; Niemann-Pick = cherry-red spot + HSM'],
        ['Q3', 'Fluid Mosaic Model',
         'Singer & Nicolson 1972; amphipathic; integral vs peripheral; cholesterol = fluidity buffer; glycocalyx',
         'Cholesterol ↑ at cold temps prevents rigidity; ↑ unsaturated FA = more fluid'],
        ['Q4', 'Membrane Transport',
         'Na⁺/K⁺-ATPase (3Na out, 2K in, 1 ATP); SGLT1/SGLT2; clathrin-coated pits; digoxin',
         'Primary = ATP directly; Secondary = uses Na⁺ gradient; facilitated = still passive'],
        ['Q5', 'Carbohydrates + GAGs',
         'Aldose vs ketose; sucrose α1→β2; lactose β1→4; Hyaluronic acid not protein-bound; heparin = anticoagulant',
         'Heparin = most sulfated; Hyaluronic acid = only non-protein-linked GAG; Pompe = glycogen LSD'],
    ],
    col_widths=[1.2*cm, 3.5*cm, 7.5*cm, CONTENT_W-12.2*cm],
    hdr_color=C_NAVY
))

story.append(sp(0.4))

story.append(section_head('Disorders Quick Reference'))
story.append(make_table(
    ['Disorder', 'Category', 'Key Defect', 'Hallmark Feature'],
    [
        ['MELAS',               'Mitochondrial',    'mt-tRNAᴸᵉᵘ mutation',         'Stroke-like episodes, lactic acidosis, <40 yrs'],
        ['MERRF',               'Mitochondrial',    'mt-tRNAᴸʸˢ mutation',         'Myoclonus, ragged-red fibers, ataxia'],
        ['LHON',                'Mitochondrial',    'Complex I (ND1/4/6)',           'Bilateral painless vision loss; young males'],
        ['Kearns-Sayre',        'Mitochondrial',    'Large mtDNA deletion',          'Ptosis, ophthalmoplegia, heart block'],
        ['Gaucher\'s',          'LSD (sphingolipid)','Glucocerebrosidase↓',          'Hepatosplenomegaly, bone pain, Gaucher cells'],
        ['Tay-Sachs',           'LSD (sphingolipid)','Hexosaminidase A↓',            'Cherry-red spot, neurodegeneration, NO HSM'],
        ['Hurler\'s (MPS I)',   'MPS (GAG)',        'α-L-Iduronidase↓',             'Coarse facies, corneal clouding, gargoylism'],
        ['Pompe\'s',            'LSD (glycogen)',   'Acid α-glucosidase↓',           'HCM, floppy baby, hepatomegaly'],
        ['Familial Hyperchol.', 'Transport defect', 'LDL receptor (RME defect)',     'Premature atherosclerosis, tendon xanthomas'],
    ],
    col_widths=[4*cm, 3.5*cm, 4*cm, CONTENT_W-11.5*cm],
    hdr_color=C_GREY
))

story.append(sp(0.4))
story.append(note('Sources: Guyton & Hall Textbook of Medical Physiology | Junqueira\'s Basic Histology | '
                  'Histology: A Text and Atlas (Pawlina) | Harper\'s Illustrated Biochemistry'))

# ── BUILD PDF ─────────────────────────────────────────────────────────────────
output_path = '/home/daytona/workspace/mbbs-revision/MBBS_Quick_Reference.pdf'
doc = SimpleDocTemplate(
    output_path,
    pagesize=A4,
    leftMargin=MARGIN, rightMargin=MARGIN,
    topMargin=1.5*cm, bottomMargin=1.2*cm,
    title='MBBS Quick Reference — Cell Biology & Biochemistry',
    author='Orris Medical',
    subject='MBBS Exam Revision'
)
doc.build(story, onFirstPage=add_page_decorations, onLaterPages=add_page_decorations)
print(f'PDF created: {output_path}')

Running Command

cd /home/daytona/workspace/mbbs-revision && python3 make_pdf.py 2>&1

Running Command

ls -lh /home/daytona/workspace/mbbs-revision/MBBS_Quick_Reference.pdf

Your PDF is ready. Download it here:

MBBS Quick Reference

PDF Document · PDF

What's inside the PDF

The document is 6 pages, A4, fully formatted with colour-coded sections:

Page	Content
Cover	Table of contents with all 5 topics and subtopics
Page 2	Q1 Mitochondria - structure table, structure flowchart, ATP synthesis flowchart, functions table, disorder classification flowchart, disorders table (MELAS/MERRF/LHON/KSS/Leigh/Pearson)
Page 3	Q2 Lysosomes - structure, biogenesis flowchart (ER→Golgi→lysosome), types, functions, LSD classification tree, 7-disorder table
Page 4	Q3 Fluid Mosaic Model - components table, labelled ASCII diagram, properties flowchart, asymmetry, membrane functions
Page 5	Q4 Membrane Transport - master classification flowchart, simple diffusion + Fick's law, facilitated diffusion table, Na⁺/K⁺-ATPase step-by-step, RME flowchart, clinical correlates (digoxin, SGLT2 inhibitors)
Page 6	Q5 Carbohydrates - classification flowchart, monosaccharide table, polysaccharide comparison, GAG classification flowchart, GAG table, proteoglycan structure, clinical significance + Rapid Review one-page summary of all 5 questions

Each section ends with a Key Words box highlighting the terms most likely to appear in MBBS exams.

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