# Amyloidosis for NEET PG Pathology: Congo Red, AL vs AA vs ATTR, Kidney and Heart Involvement, Diagnosis

Source: https://tracknation.in/story/amyloidosis-for-neet-pg-pathology-congo-red-al-vs-aa-vs-attr-kidney-and-heart-involvement-diagnosis (TrackNation — free UPSC notes with PYQs)

> NEET PG Pathology: what amyloid is, H&E, PAS and Congo red with apple-green birefringence, AL, AA, hereditary and wild-type transthyretin and dialysis amyloid, organ involvement from kidney and heart to tongue and raccoon eyes, and diagnosis by fat aspirate and organ biopsy, with a diagram, hooks, vignette MCQs and cards.

## Start Here

🎯 **Exam priority: Moderate.** *Expect: the Congo red finding, which protein makes AL vs AA, the inflammatory diseases that
cause AA, dialysis amyloid, organs involved, and the best biopsy site.*

CBME mapping: **PA 9.1–9.2**.

*Types of amyloidosis and how amyloid is identified. Drawn by TrackNation.*

## What Amyloid Is

- Extracellular deposits of insoluble ~10 nm fibrils made of misfolded proteins arranged as **beta-pleated sheets**, with serum
amyloid P component and glycosaminoglycans. Deposits are inert but crowd organs; some prefibrillar oligomers are directly toxic.

- **Stains**: pink on H&E; PAS and Alcian blue positive; most characteristic is **apple-green birefringence** under
polarised light after **Congo red**. Electron microscopy shows non-branching 10 nm fibrils. Organs look waxy at autopsy.

## Types

- **AL**: clonal immunoglobulin light chains from a plasma cell or B-cell clone; 10–20% of myeloma patients develop it.
Targets skin, nerves, heart, gut and tongue (macroglossia), kidney, liver, spleen, vessels.

- **AA**: serum amyloid A, an acute-phase reactant raised by IL-1, TNF and IL-6 in chronic infection (TB, bronchiectasis,
osteomyelitis, leprosy) or inflammation (rheumatoid and juvenile arthritis, Crohn disease, familial Mediterranean fever). Prefers kidneys, spleen, liver,
adrenals and lymph nodes.

- **Hereditary ATTRv**: mutant transthyretin — the commonest hereditary type; neuropathy (carpal tunnel first), kidney and heart
disease; liver transplant can remove the source. **ATTRwt**: normal transthyretin in the hearts of older men. Typing matters: chemotherapy
is for AL, not ATTR.

- **β2-microglobulin** amyloid in long-term haemodialysis. **Localised**: amyloid beta in the brain (Alzheimer disease,
amyloid angiopathy); light chains elsewhere.

## Organs and Diagnosis

- **Kidney**: glomerular deposits → proteinuria → nephrotic syndrome or end-stage disease. **Heart**: restrictive
(infiltrative) cardiomyopathy, diastolic failure, low ECG voltage despite a thick wall. **Liver**: painless, sometimes massive,
hepatomegaly. Peripheral neuropathy; bruising around the eyes ("raccoon eyes") from fragile vessels.

- **Diagnosis**: show fibrils in tissue. Abdominal fat aspirate finds amyloid in ~80% of AL (under 25% of ATTRwt); kidney or
heart biopsy is nearly 100% sensitive when involved. Then type it — mass spectrometry is the most sensitive and specific.

## Traps the Examiner Sets

- Apple-green birefringence needs Congo red *and* polarised light.

- AL = light chains (myeloma, macroglossia); AA = serum amyloid A (TB, RA, FMF).

- Dialysis amyloid = β2-microglobulin; brain = amyloid beta.

- Thick heart wall but low ECG voltage = infiltrative (amyloid).

## Memory Hooks & Shortcuts

*Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.*

- 🧠 **Congo goes Green in Polarised light** — Congo red apple-green birefringence

- 🧠 **AL = Light chains; AA = Acute-phase (SAA)** — AL vs AA

- 🧠 **Dialysis Delivers β2M** — dialysis amyloid

- 🧠 **Thick wall, Tiny voltage = amyloid** — cardiac amyloid ECG

- 🧠 **Fat first, then the organ** — biopsy order

## Rapid-Revision Cards

- Extracellular insoluble ~10 nm fibrils, beta-pleated sheets.

- Serum amyloid P + glycosaminoglycans.

- H&E pink; PAS/Alcian blue +; Congo red → apple-green under polarised light.

- Non-branching 10 nm fibrils.

- Light chains; myeloma (10–20%); macroglossia.

- Serum amyloid A; TB, bronchiectasis, RA, Crohn, FMF.

- Kidney, spleen, liver, adrenals, nodes.

- Commonest hereditary; carpal tunnel first.

- Older men's hearts; no chemotherapy.

- β2-microglobulin.

- Amyloid beta — Alzheimer, angiopathy.

- Glomerular → proteinuria → nephrotic.

- Restrictive; thick wall, low ECG voltage.

- Fragile amyloid vessels.

- Abdominal fat (~80% AL).

- Mass spectrometry best.

## Sources

*Facts in this article were checked against these documents.*

- MSD Manual Professional: Amyloidosis — Merck & Co. (MSD Manuals), reviewed 2025–26 (link)

- MSD Manual Professional: Restrictive Cardiomyopathy — Merck & Co. (MSD Manuals), reviewed 2025–26 (link)

- Competency Based Undergraduate Curriculum, Pathology (PA 9) — National Medical Commission, 2024

## Test Yourself: Practice Questions

Twenty-two questions in NEET PG style, most of them clinical vignettes.

## Practice Questions (NEET PG pattern)

*Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer
was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.*

**Q1.** A kidney biopsy stained with Congo red and viewed under polarised light shows apple-green birefringence. The deposit is

- (a) amyloid

- (b) fibrin

- (c) collagen

- (d) immune complexes

**Answer: (a)** — Most characteristic amyloid stain finding.

**Q2.** Amyloid fibrils are arranged as

- (a) beta-pleated sheets

- (b) random coils

- (c) alpha helices only

- (d) triple helices

**Answer: (a)** — Approximately 10 nm insoluble fibrils.

**Q3.** Besides the fibrillar protein, all amyloid deposits contain

- (a) haemosiderin

- (b) serum amyloid P component and glycosaminoglycans

- (c) calcium phosphate

- (d) immunoglobulin heavy chains only

**Answer: (b)** — MSD.

**Q4.** On routine H&E, amyloid appears

- (a) black

- (b) blue and intracellular

- (c) pink, amorphous and extracellular

- (d) unstained

**Answer: (c)** — Also PAS and Alcian blue positive.

**Q5.** Electron microscopy of an amyloid-laden heart biopsy shows

- (a) viral particles

- (b) non-branching fibrils about 10 nm wide

- (c) branching fibrils 100 nm wide

- (d) dense deposits on the basement membrane

**Answer: (b)** — MSD.

**Q6.** A patient with multiple myeloma develops an enlarged tongue, heavy proteinuria and heart failure. The amyloid protein is

- (a) transthyretin

- (b) immunoglobulin light chain (AL)

- (c) serum amyloid A (AA)

- (d) β2-microglobulin

**Answer: (b)** — Macroglossia is common in AL; 10–20% of myeloma patients develop AL.

**Q7.** A man with long-standing untreated tuberculosis develops nephrotic syndrome. Renal biopsy shows amyloid. The precursor protein is

- (a) serum amyloid A (acute-phase reactant)

- (b) amyloid beta

- (c) light chain

- (d) transthyretin

**Answer: (a)** — AA follows chronic infection or inflammation.

**Q8.** Which condition is a recognised cause of AA amyloidosis?

- (a) familial Mediterranean fever

- (b) multiple myeloma

- (c) long-term haemodialysis

- (d) Alzheimer disease

**Answer: (a)** — Also TB, bronchiectasis, osteomyelitis, leprosy, RA, Crohn disease.

**Q9.** In AA amyloidosis, serum amyloid A rises because

- (a) plasma cells make it

- (b) the kidney fails to clear it

- (c) inflammatory cytokines (IL-1, TNF, IL-6) increase its hepatic synthesis

- (d) it is inherited

**Answer: (c)** — An acute-phase reactant.

**Q10.** AA amyloidosis typically targets the

- (a) brain only

- (b) skin only

- (c) kidneys, spleen, liver, adrenals and lymph nodes

- (d) tongue only

**Answer: (c)** — Heart and nerves late.

**Q11.** A patient on haemodialysis for many years develops amyloid deposits. The protein is

- (a) light chain

- (b) serum amyloid A

- (c) transthyretin

- (d) β2-microglobulin

**Answer: (d)** — Less common with high-flow membranes.

**Q12.** The commonest type of hereditary amyloidosis is caused by mutant

- (a) transthyretin (ATTRv)

- (b) immunoglobulin

- (c) amyloid beta

- (d) serum amyloid A

**Answer: (a)** — Neuropathy, kidney disease, cardiomyopathy.

**Q13.** In hereditary transthyretin amyloidosis, the neurological feature that commonly comes first is

- (a) seizures

- (b) carpal tunnel syndrome

- (c) dementia

- (d) optic neuritis

**Answer: (b)** — Then sensorimotor and autonomic neuropathy.

**Q14.** An elderly man has heart failure with a thick-walled heart; amyloid is made of normal (wild-type) transthyretin. Why must it be typed carefully?

- (a) chemotherapy is for AL amyloidosis and would be wrong for ATTRwt

- (b) it is always fatal

- (c) it is infectious

- (d) it needs dialysis

**Answer: (a)** — ATTRwt mainly affects the heart of older men.

**Q15.** Amyloid deposits in the brain in Alzheimer disease are made of

- (a) light chains

- (b) serum amyloid A

- (c) transthyretin

- (d) amyloid beta protein

**Answer: (d)** — Also cerebral amyloid angiopathy.

**Q16.** In renal amyloidosis, deposits typically start in the

- (a) ureter

- (b) renal artery only

- (c) glomerular membrane, causing proteinuria and nephrotic syndrome

- (d) renal pelvis

**Answer: (c)** — About 15% affect tubules instead.

**Q17.** Cardiac amyloidosis causes which type of cardiomyopathy?

- (a) dilated

- (b) arrhythmogenic right ventricular

- (c) restrictive (infiltrative), with diastolic dysfunction

- (d) hypertrophic obstructive

**Answer: (c)** — Also sarcoidosis among infiltrative causes.

**Q18.** Echocardiography shows a thick ventricular wall, but the ECG shows low voltage. This combination suggests

- (a) amyloid infiltration

- (b) pericardial effusion only

- (c) athlete's heart

- (d) hypertensive hypertrophy only

**Answer: (a)** — MSD.

**Q19.** A patient with AL amyloidosis bruises around the eyes after coughing. The cause is

- (a) trauma only

- (b) low platelets

- (c) amyloid weakening small blood vessels

- (d) vitamin K deficiency

**Answer: (c)** — 'Raccoon eyes'.

**Q20.** The simplest first biopsy to look for systemic AL amyloidosis is

- (a) bone marrow only

- (b) skin of the scalp

- (c) aspiration of subcutaneous abdominal fat (~80% positive in AL)

- (d) brain biopsy

**Answer: (c)** — If negative, biopsy an involved organ (kidney/heart nearly 100%).

**Q21.** The most sensitive and specific way to identify which protein forms the amyloid is

- (a) mass spectrometry

- (b) H&E staining

- (c) serum protein electrophoresis

- (d) Congo red alone

**Answer: (a)** — Immunohistochemistry can give false positives.

**Q22.** At autopsy, organs heavily infiltrated by amyloid look

- (a) haemorrhagic

- (b) black

- (c) cystic

- (d) waxy

**Answer: (d)** — MSD.

### Active Recall

From memory: describe what amyloid is and how it stains; name the protein and causes of AL, AA, ATTRv, ATTRwt, dialysis and brain amyloid; list the organs involved and their signs; and outline how amyloidosis is diagnosed and typed.