A 42-year-old man presents to his primary care provider complaining of foamy urine for the last 2 weeks. He has also begun to notice swelling in his hands and feet, and he says that his shoes have not been fitting normally. On exam, the patient has a temperature of 98.8°F (37.1°C), blood pressure is 132/84 mmHg, pulse is 64/min, and respirations are 12/min. The patient has 2+ pitting edema bilaterally up to his shins. A 24-hour urine study is found to contain 9.0 g of protein. The patient is referred to a specialist and undergoes a renal biopsy. On light microscopy, the glomeruli demonstrate basement membrane thickening. On electron microscopy, subepithelial deposits are seen. Which of the following is a characteristic of this patient’s disease?

Antibodies to phospholipase A2 receptor

Antibodies to alveolar basement membrane

Loss of podocyte foot processes

A 36-year-old man undergoes ileocecal resection after a gunshot injury. The resected ileocecal segment is sent for histological evaluation. One of the slides derived from the specimen is shown in the image. Which of the following statements regarding the structure marked within the red circle is correct?

This structure can become a site of entry of certain microorganisms including S. typhi.

This structure can be only found in the colon.

These structures mostly contain M-cells.

This structure only appears in case of bacterial infection.

Infants have the largest amount of these structures within their intestinal wall.

A 45-year-old man presents to the office with complaints of facial puffiness and mild swelling in his lower back. He denies chest pain, blood in the urine, or fever. He was recently diagnosed with colon cancer. The vital signs include a blood pressure of 122/78 mm Hg, a pulse of 76/min, a temperature of 36.9°C (98.4°F), and a respiratory rate of 10/min. On physical examination, there is mild facial puffiness that is pitting in nature and presacral edema. His other systemic findings are within normal limits. Urinalysis shows: pH 6.2 Color light yellow RBC none WBC 3–4/HPF Protein 4+ Cast oval fat bodies Glucose absent Crystal none Ketone absent Nitrite absent 24 hours urine protein excretion 4.8 g A renal biopsy is ordered and diffuse capillary and basement membrane thickening is noted. Which of the following findings is expected to be present if an electron microscopy of the biopsy sample is performed?

Massive amyloid deposition and spicular aggregates

A 4-year-old male is accompanied by his mother to the pediatrician. His mother reports that over the past two weeks, the child has had intermittent low grade fevers and has been more lethargic than usual. The child’s past medical history is notable for myelomeningocele complicated by lower extremity weakness as well as bowel and bladder dysfunction. He has been hospitalized multiple times at an outside facility for recurrent urinary tract infections. The child is in the 15th percentile for both height and weight. His temperature is 100.7°F (38.2°C), blood pressure is 115/70 mmHg, pulse is 115/min, and respirations are 20/min. Physical examination is notable for costovertebral angle tenderness that is worse on the right. Which of the following would most likely be found on biopsy of this patient’s kidney?

Tubular colloid casts with diffuse lymphoplasmacytic infiltrate

Replacement of renal parenchyma with foamy histiocytes

Diffusely necrotic papillae with dystrophic calcification

Mononuclear and eosinophilic infiltrate

Destruction of the proximal tubule and medullary thick ascending limb

Electron microscopy in histology for USMLE Step 1: High-Yield Anatomy Lessons

EM Fundamentals - Seeing the Unseen

Electron Microscopy (EM) uses an electron beam and magnetic lenses in a vacuum to achieve high resolution, far exceeding light microscopy. Essential for viewing organelles.
Types:
- Transmission (TEM): 2D image of internal ultrastructure. Electrons pass through the specimen. 📌 TEM shows Thin, Two-dimensional slices.
- Scanning (SEM): 3D surface view. Electrons scan the surface. 📌 SEM Sees the Surface.

⭐ Osmium tetroxide (OsO₄) is a heavy metal stain used in EM to fix and stain lipids, making them appear electron-dense (dark).

SEM vs TEM: Electron Beam Paths and Components

Microscope Showdown - TEM vs. SEM

📌 TEM = Transmits Through for a Two-D view. SEM = Scans Surface for a Superficial 3D view.

Feature	Transmission EM (TEM)	Scanning EM (SEM)
Image	2D projection (flat)	3D surface rendering
View	Internal ultrastructure (e.g., organelles)	Surface topography (e.g., cell projections)
Mechanism	Electron beam passes Through a thin slice	Electron beam Scans over a coated surface
Resolution	Higher (sub-nanometer)	Lower (nanometer)
Key Use	Visualizing intracellular structures, viruses	Examining cell surface features, tissues

⭐ Exam Favorite: SEM is classically used to visualize the detailed 3D topography of structures like renal podocytes, the stereocilia of the inner ear, or intestinal microvilli, which are often flattened and indistinguishable in TEM.

The Fix-Up - Specimen Prep Steps

Fixation: Glutaraldehyde cross-links proteins; Osmium tetroxide ($OsO_4$) fixes lipids.
Embedding: Epoxy resin provides stability for cutting under the electron beam.
Sectioning: Ultramicrotome with a diamond knife creates ultrathin sections (60-90 nm).
Staining: Electron-dense heavy metals (Lead citrate, Uranyl acetate) scatter electrons to create contrast.

⭐ Osmium tetroxide is key for membrane visualization. It binds to lipids, making membranes electron-dense and appear as dark lines in the final image.

Clinical Snapshots - What EM Reveals

Electron microscopy (EM) reveals ultrastructural details invisible on light microscopy, clinching diagnoses for specific diseases.

Kidney Biopsy:
- Minimal Change Disease: Diffuse effacement (flattening) of podocyte foot processes.
- Membranous Nephropathy: Subepithelial immune deposits creating a “spike and dome” pattern.
- Alport Syndrome: Lamellated, basket-weave appearance of the glomerular basement membrane.
Other Tissues:
- Kartagener Syndrome: Absence of dynein arms in cilia, causing immotility.
- Langerhans Cell Histiocytosis: Rod-shaped Birbeck granules (“tennis rackets”) within cytoplasm.

⭐ The pathognomonic finding in Minimal Change Disease is podocyte effacement, which is only visible on EM; light microscopy appears normal.

Podocyte foot process effacement in minimal change disease

High‑Yield Points - ⚡ Biggest Takeaways

Electron microscopy (EM) offers superior resolution over light microscopy, visualizing cellular ultrastructure.

Transmission EM (TEM) provides 2D images of internal components like organelles and inclusions.

Scanning EM (SEM) generates 3D surface views, ideal for studying cell topography like microvilli.

Key for diagnosing kidney diseases by revealing podocyte effacement in the glomerulus.

Identifies viral particles and bacterial structures not visible with light microscopy.

Requires specialized tissue preparation, including glutaraldehyde fixation and heavy metal staining.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play