🖇 I. Endoplasmic Reticulum (ER)

📌 Definition

A membrane network within cytoplasm.
“Endo” = inside, “plasmic” = cytoplasm, “reticulum” = network.

📌 Classification & Structure

Two types:
1. Smooth Endoplasmic Reticulum (SER)
  → smooth surface.
2. Rough Endoplasmic Reticulum (RER)
  → rough surface due to ribosomes attached.
  → Continuous tubes/sacs connected together.
  → Continuous with nuclear membrane.

🟠 Nature

Classified as a membranous organelle.
Structure: delicate tubules / cisternae (histological term).

📌 Distribution & Appearance

Present in all cells.

1. RER

Abundant in cells specialized in protein synthesis.
(Exam Point) “Rough = Protein.”

Light Microscopy (LM):

Not directly visible.
If abundant → cytoplasm appears basophilic (blue) due to RNA in ribosomes binding basic dyes (H&E).

Electron Microscopy (EM):

Appears as connected tubules/sacs with rough outer surface (ribosomes = dark electron-dense granules).

2. SER

Abundant in cells with lipid/fat metabolism.
LM: not visible.
EM: network of smooth-surfaced tubules.

📌 Functions of ER

1. RER – Protein Synthesis & Modification

Step 1: Translation occurs at ribosomes using mRNA from nucleus.
Step 2: Ribosomes attach to RER; new proteins enter RER tubules.
Step 3: Proteins undergo initial modification (defects → hereditary diseases).
Step 4: Modified protein + RER membrane pinch off → vesicle.
Step 5: Vesicle moves to Golgi apparatus for further processing.

(Note: Proteins form structural, enzymatic, and hormonal elements except steroid hormones.)

2. SER – Lipid & Detoxification Functions

(Exam Point) Synthesis of lipids, phospholipids, and steroid hormones.
(Exam Point) Detoxification of toxins & drugs (mainly in liver).
(Exam Point) Calcium storage in muscle cells for contraction.

🖇 II. Mitochondria

📌 Definition

Known as the Powerhouse of the Cell.

📌 Distribution & Size

Present in all cells except:
- Red Blood Cells (RBCs)
- Terminal Keratinocytes
(Exam Point) Size not required for memorization.

📌 Appearance (Light Microscopy)

Not visible with routine H&E.
Seen only with special stains (Exam Point):
1. Iron Hematoxylin
2. Janus Green
3. Acid Fuchsin
Appear as rods or spheres.

📌 Appearance (Electron Microscopy)

Surrounded by two membranes (double unit membranes).

1. Outer Mitochondrial Membrane (OMM):

Smooth, permeable.

2. Inner Mitochondrial Membrane (IMM):

Folded inward → Cristae (shelf-like structures).
Selectively permeable.
Contains Cardiolipin → responsible for selective permeability.

3. Intermembrane Space:

Between OMM & IMM.
Contains H⁺ ions for respiratory chain reactions.

4. Mitochondrial Matrix:

Fluid inside IMM.
IMM folds (cristae) → increase surface area. (Exam Point)

5. F1 Particles (Elementary Particles):

On IMM surface facing matrix.
Tennis racket appearance. (Exam Point)
Contain enzymes for ATP synthesis.

📌 Mitochondrial DNA & Division

Contains its own DNA → can divide independently (non-synchronous).
Mitochondrial DNA:
- Circular shape, in matrix.
- 1% of total cell DNA.
Nuclear DNA:
- Double helix, in nucleus.
- 99% of total DNA.

📌 Types (EM Classification)

Orthodox Type: clear cristae & matrix → resting cells.
Condensed Type: dense cristae, indistinct matrix → active cells.

🖇 III. Golgi Apparatus (GA)

📌 Definition

Membranous organelle responsible for secretion. (Exam Point)

📌 Distribution & Location

Present in all cells.
Prominent in secretory cells.

📌 Appearance (Light Microscopy)

Not seen with routine H&E.
Negative Golgi Image (Exam Point):
- Seen as clear unstained area near nucleus in highly basophilic cells (e.g. plasma cells).
Special Stains: Silver → brown filaments (Fittaniya).

📌 Appearance (Electron Microscopy)

Series of flattened sacs (cisternae/saccules) stacked like plates.
Two faces:
1. Cis / Forming / Convex Face: faces RER & nucleus.
2. Trans / Mature / Concave Face: faces cell membrane → site of secretion.

📌 Functions

Post-translational modification & packaging of proteins from RER.
Modification:
- Glycosylation → glycoproteins.
- Trimming of protein chains.
Secretion:
- Final vesicles pinch off from Trans face.
Membrane recycling: forms membranes of RER & cell membrane.
Lysosome formation: produces lysosomal enzymes.

🖇 IV. Lysosomes

📌 Definition

Digestive system of the cell.

📌 Contents & Origin

Contain hydrolytic enzymes (digestive enzymes).
Enzymes synthesized in RER, packaged by Golgi apparatus.

📌 Appearance

LM: not visible normally.
EM: membrane-bound vesicles with enzyme content.

📌 Classification (Functional State)

Primary Lysosome:
- Newly formed, inactive, from Golgi.
- Has not yet fused with target.
Secondary Lysosome:
- Formed after fusion with a target vesicle.
- Subtypes:
- - Phagolysosome: fusion with Phagosome (solid material).
  - Multivesicular Body: fusion with Pinocytic vesicle (fluid).
  - Autophagic Vacuole: digestion of cell’s own organelles (self-eating).
Residual Body (Exam Point):
Lipofuscin Pigment (Exam Point):
- Indigestible waste left after digestion.
- Normally expelled.
- Accumulates in nerve cells & cardiac muscle cells (non-dividing).
- Represents undigested residual bodies.

📌 Functions

Digestion & elimination of harmful substances (internal/external).
Cell metabolism: activates thyroid hormone.
Post-mortem autolysis:
- After death, lysosomal membranes rupture → enzymes digest cell → decomposition.

🚨 Clinical Note

Lysosomal Storage Diseases: genetic defects in lysosomal enzymes → substrate accumulation.
- Example: Gaucher’s Disease – deficiency of Glucocerebrosidase → buildup of Glucocerebroside in tissues (muscle, brain, joints).

🖇 V. Peroxisomes

📌 Definition

Structurally resemble lysosomes but contain oxidative enzymes.

📌 Contents & Functions

(Exam Point) Contain oxidative enzymes (vs. lysosomal hydrolytic enzymes).
Functions:
1. Fatty acid oxidation.
2. Alcohol detoxification.
3. Use oxidative enzymes for metabolism.

📌 Origin

(Exam Point) Not derived from Golgi apparatus.

📌 Structure (EM)

Membrane-bound vesicles.
May appear as coated vesicles (protection from digestion).

Histology