CLASE TEÓRICA 4 - METABOLOPATÍAS PARTE 2

Diabetes Mellitus: Types and Pathophysiology

Type 1 Diabetes Mellitus

• The incidence of Type 1 diabetes mellitus is between 10% to 20%, primarily affecting young patients under 20 years old with a sudden onset.

• Patients typically present with normal weight; genetic inheritance plays a minor role, accounting for less than 20%.

• The pathogenesis is predominantly autoimmune, leading to the destruction of pancreatic beta cells, characterized by inflammation mediated by lymphocytes.

Type 2 Diabetes Mellitus

• In contrast, Type 2 diabetes has a much higher incidence (80%-90%) in the general population, usually presenting in adults over 40 years old with gradual onset.

• Risk factors include obesity, sedentary lifestyle, and significant genetic influence (50%-60%), indicating multifactorial inheritance involving both genetic and environmental factors.

• There is insulin resistance or deficiency at the tissue level; pancreatic inflammation is absent but may show fibrosis with normal or reduced beta cells.

Metabolic Complications

• Increased levels of fatty acids and cholesterol are common; ketosis can occur alongside complications from non-enzymatic glycosylation leading to advanced glycation end-products (AGE).

• Intracellular hyperglycemia disrupts cellular pathways causing cell mortality and edema, potentially resulting in metabolic cirrhosis and hyperglycemic hyperosmolar coma.

Organ-Specific Complications

Ocular Complications

• Diabetic retinopathy includes microangiopathy classifications affecting retinal health due to vascular changes.

Renal Complications

• Diabetic nephropathy affects glomeruli and tubules; chronic renal insufficiency may develop due to various renal pathologies.

Neurological Complications

• Peripheral neuropathy occurs alongside central nervous system alterations due to diabetes-related physiological changes.

Histopathological Findings

Pancreas

• Microscopic examination reveals fibrosis and inflammatory infiltrates disrupting normal pancreatic architecture.

Kidney

• Diabetic kidneys may exhibit size reduction with surface irregularities; specific lesions like diffuse glomerulosclerosis are noted along with nodular forms related to diabetes.

Vascular Changes

• Atherosclerosis leads to thickened vascular walls reducing lumen size; diabetic patients have compromised immune responses increasing infection risks.

Tubular Changes

Glucosuria Effects

• High blood glucose levels lead to significant glucosuria that can cause tubular cell damage known as Armani-Einstein cells which are reversible upon normalization of glucose levels.

Glomerular Changes

• Nodular glomerulosclerosis presents as capillary luminal narrowing due to glycemic deposits impacting kidney function significantly.

Retinal Changes

Retinopathy Progression

Diabetes Complications and Related Conditions

Diabetic Retinopathy and Cataracts

• Diabetic patients may experience retinal detachment and cataracts due to sorbitol accumulation in the lens, leading to opacification.

• Insensitivity in diabetic patients can lead to skin infections, progressing to gangrene, which is characterized by necrosis of vital tissues.

Gangrene and Its Consequences

• Gangrene can extend to bones, causing osteomyelitis or systemic infection that may result in septic shock, posing a risk of death.

• Common causes of death in diabetes include heart failure, acute myocardial infarction, renal failure, strokes, infections, and gangrene.

Gout: A Metabolic Disorder

• Gout is characterized by hyperuricemia and urate crystal deposits primarily affecting distal extremities where temperatures are lower.

• The condition leads to chronic granulomatous inflammation affecting various tissues including cartilage and kidneys.

Types and Causes of Gout

• Primary gout is genetically determined by enzymatic defects; secondary gout arises from chronic renal insufficiency or excessive diuretic use.

• Chronic forms of gout can cause debilitating disorders within the locomotor system due to joint damage and bone destruction.

Amiloidosis: An Overview

• Amiloidosis involves progressive deposition of abnormal protein substances that lead to cellular atrophy through interstitial accumulation.

• Different types of amyloids exist (e.g., AA associated with inflammatory conditions), impacting various organs like the brain (Alzheimer's), heart, kidneys, etc.

Systemic vs. Localized Amiloidosis

• Amyloidosis can be localized (e.g., cerebral or cardiac forms related to specific diseases like diabetes type 2 or medullary thyroid carcinoma).

Understanding Amyloidosis and Its Impact on Renal Function

Mechanisms of Amyloidosis

• The presence of neoplastic plasma cells produces defective light chains of immunoglobulin, leading to systemic effects and renal implications, particularly proteinuria due to massive excretion of these light chains.

• Familial Mediterranean fever and hereditary neuropathies are among various conditions associated with amyloidosis, which can lead to renal failure, neuropathies, hepatic alterations, and cardiovascular diseases.

Diagnostic Challenges

• Amyloid proteins are eosinophilic with hematoxylin staining; they can be mistaken for other deposits mediated by glycoproteins or immune complexes due to their similar staining characteristics.

• Special stains like Congo red can be used under polarized light to identify amyloid deposits in glomeruli, confirming the presence through characteristic birefringence.

Macroscopic Features of Renal Amyloidosis

• Macroscopically, kidneys affected by amyloidosis exhibit increased size and a pale grayish color typical of amyloid deposits at the renal level.

• Staining techniques such as Lugol's solution reveal small nodules that test positive for brown mahogany coloration; further special staining with 5% sulfuric acid shows blue-green nodules indicative of amyloid.

Histological Examination