5.10. Impaired metabolism of carbohydrates, lipids, and bilirubin. Diabetes mellitus. Morphology of alcoholism quiz

What are the accumulating substances, their localization and Pathogenesis mechanisms

• Substance types:

  • Normal (e.g. fat, water, protein) in excess

  • Abnormal (e.g. pigments, drugs)

• Locations:

  • Intracellular

  • Interstitial

  • Inside hollow organs

• Mechanisms:

  • Increased intake/synthesis

  • Impaired degradation or excretion

What is lipidosis and define the different forms of it

Subtype	Description	Example
Steatosis	Triglycerides in parenchymal cells (like liver, heart)	Fatty liver (hepatic steatosis)
Obesity (Adipositas)	Triglycerides in adipocytes (fat cells)	Visceral and subcutaneous fat expansion
Systemic lipidosis (Tesaurismosis)	Lipid accumulation in macrophages	Gaucher’s disease
Cholesterol crystals in arteries	Leads to atherosclerosis	CAD, stroke risk

Cause and macro/microscopic findings in steatosis

• Cause: Hypoxia (e.g., heart failure), toxins (e.g., alcohol, CCl₄), obesity

• Macroscopic: Yellow, greasy, enlarged liver

• Microscopic: Clear vacuoles in hepatocytes (fat droplets)

Cause and macro/microscopic findings in cardiac steatosis

• Caused by chronic hypoxia, malnutrition (e.g., cachexia, diphtheria)

• Macroscopic: Tiger-striped heart (yellow streaks in myocardium)

• Microscopic: Vacuolated cytoplasm in cardiac muscle cells

What is obesity (adipositas), etiology localization and complications

• Definition: Generalized increase in adipose tissue mass.

• Etiology:

  • High-calorie diet (especially saturated fats)

  • Endocrine disorders (e.g., Cushing’s)

  • Genetic and hypothalamic dysfunction

• Localization:

  • Subcutaneous fat (under skin)

  • Visceral fat (around organs: liver, heart, intestines)

• Complications:

  • Metabolic: insulin resistance → diabetes mellitus type II

  • Vascular: atherosclerosis, hypertension

  • Biliary: ↑ cholesterol → gallstones

What is this

Cardiac Obesity (Fatty Heart)

• Seen in advanced obesity

• Excess epicardial fat may compress coronary arteries

• Heart may appear large, with thick fat covering

Which disease can be caused by cholesterol and cholesterol esters and what are they

Location	Condition
Arterial walls	Atherosclerosis (plaques with lipid cores)
Skin & tendons	Xanthomas (yellow plaques, often in hyperlipidemia)
Gallbladder submucosa	Cholesterolosis (foamy macrophages in mucosa, “strawberry gallbladder”

What are the arrows pointing at?

Foamy macrophages: Lipid-laden phagocytes seen in atherosclerosis and xanthomas

What is jaundice?

• Jaundice = yellow discoloration of skin and sclera due to dissolved bilirubin or increased amount of bile pigments in blood or tissue fluids

What are the types of jaundice

Type	Site	Bilirubin Type	Mechanism
Prehepatic	Before liver	unconjugated	Hemolysis → overproduction
Hepatic	In liver	unconjugated or both	Impaired uptake, conjugation, or excretion
Posthepatic	After liver	conjugated	Obstruction (e.g., gallstones, tumor)

What are stones and why do they form?

Stones (s. concretions, calculi)– accumulations of salts in cavities or excreting ducts.

• Stones form in ducts/organs due to:

  • Supersaturation of salts (e.g., Ca²⁺, uric acid)

  • Formation of a nucleation center

  • Stasis or impaired excretion

Name the different localization of stones

Location	Stone Name
Gallbladder	Cholelith (gallstone)
Kidney/UT	Urolith (renal stone)
Salivary glands	Sialolith
Pancreatic duct	Pancreolith
Appendix	Coprolith (hard fecal mass)

What’s this

• Urate stones: Radiolucent, linked to gouT

what are the morphological features of stones

• Any shape, consistency and color

• Gall stones → round or cube-shaped with smooth surface, black, dark green or yellowish

• Kidney stones → calcium, phosphate, oxalate, uric acid, with rough surface, can acquire the form of calyces and pelvis

What are langerhans islets and their functions

• Langerhans islets are clusters of endocrine cells scattered throughout the pancreas.

• They make up about 1–2% of the pancreatic mass but are vital for glucose homeostasis.

What are the cell types in langerhans islets and what is their functional role

Cell Type	Hormone	Function
β-cells (70%)	Insulin	Lowers blood glucose by increasing uptake into tissues
α-cells (20%)	Glucagon	Raises blood glucose by stimulating glycogenolysis and gluconeogenesis
δ-cells	Somatostatin	Inhibits both insulin and glucagon
PP cells	Pancreatic polypeptide	Regulates pancreatic secretion activity
ε-cells	Ghrelin	Appetite regulation

Functional Role:

• These endocrine cells sense blood glucose levels and adjust hormone secretion accordingly.

• Disruption in β-cell function or mass is central to diabetes mellitus.

What is diabetes mellitus

A group of metabolic disorders characterized by the common feature of chronic hyperglycemia, resulting from:

• Defective insulin secretion

• Defective insulin action

• Or both

What is type 1 diabetes mellitus, cause, Pathogenesis and morphology

Type I Diabetes Mellitus

• Also called: Juvenile or insulin-dependent diabetes

• Cause: Autoimmune destruction of β-cells → absolute insulin deficiency

• Pathogenesis: Often involves HLA-linked immune response with T-cell–mediated insulitis

• Morphology:

  • Early: No gross changes

  • Later: Lymphocytic infiltration in islets (insulitis)

  • Islets may become atrophic or disappear

What is type 1 diabetes mellitus, cause, risk factors, Pathogenesis and morphology

Type II Diabetes Mellitus

• Also called: Adult-onset or non–insulin-dependent diabetes

• Cause: Combination of insulin resistance and relative insulin deficiency

• Risk factors:

  • Obesity

  • Sedentary lifestyle

  • Genetic predisposition

  • Gestational diabetes

• Morphology:

  • Gross: Pancreas appears more lobulated

  • Microscopy:

    • Atrophy of islets

    • Amyloid deposition in and around islets (derived from islet amyloid polypeptide or IAPP)

    • Fewer β-cells

What are other diseases that can cause diabetes mellitus

2. • Exocrine pancreas diseases: pancreatitis, neoplasms, cystic fibrosis

   • Endocrine disorders: Cushing’s syndrome, acromegaly, pheochromocytoma

   • Hormonal drugs/agents: glucocorticoids, thyroid hormones, interferon-α

   • Genetic syndromes: Down, Klinefelter, Turner syndrome

What is gestational diabetes

3. Gestational Diabetes

   • Occurs during pregnancy due to placenta producing hormones that inhibit the the functioning insulin → blood glucose is increased

   • Resolves postpartum in most cases

   • Increases risk of developing Type II DM later in life

Morphologcial features of pancreas in diabetes type 1

Type I DM

:

• Early stages: no gross changes

• Later:

  • Lymphocytic infiltration of Langerhans islets (insulitis)

  • Progressive β-cell destruction

  • Remaining islets may appear atrophic

What vascular injuries can be caused by diabetes mellitus (glucotoxicity)

Chronic high blood sugar leads to:

• Non-enzymatic glycation of proteins → reduced elasticity, protein trapping

• AGEs (Advanced Glycation End-products) promote inflammation, stiffening

• Oxidative stress → endothelial cell injury

• Smooth muscle proliferation → vascular wall thickening

• ↑ TGF-β → excessive basement membrane material

What types of vascular injuries in diabetes mellitus

1. Macroangiopathy

• Affects large & medium arteries

• Accelerates atherosclerosis

• Major complications:

  • Coronary arteries → Myocardial infarction

  • Cerebral arteries → Stroke

  • Peripheral arteries → Gangrene of extremities (diabetic foot)

2. Microangiopathy

• Affects capillaries and small arterioles

• Key features:

  • Thickened basement membranes

  • Reduced capillary function

• Organs:

  • Kidneys → diabetic nephropathy

  • Retina → diabetic retinopathy

  • Peripheral nerves → diabetic neuropathy

What is this disease called

Diabetic macroangiopathy: atherosclerosis of coronary arteries may lead to myocardial infarction

What is this disease called

Diabetic macroangiopathy: diabetic foot–focal necrosis of soft tissues of lower extremities due to atherosclerosis and polineuropathies

• Ischemia + peripheral neuropathy → tissue necrosis

• May develop ulcers, infection, gangrene

• Risk of amputation

What is this disease called

Diabetic microangiopathy: Injury of small renal blood vessels and capillaries

What does this slide show

Microscopy (PAS stain):

• Arteriolosclerosis: hyaline thickening of small arteries

• Tubular damage: thickened basement membranes

• Glomerulosclerosis:

  • Mesangial matrix expansion

  • Sclerosis (e.g., Kimmelstiel-Wilson nodules)

Morphological features of alcoholism in the nervous system

NERVOUS SYSTEM

• Alcoholic encephalopathy

  • Memory loss, confusion, ataxia

  • Wernicke’s encephalopathy (due to thiamine deficiency):

    • Classic triad: confusion, ophthalmoplegia, ataxia

• Peripheral neuropathy

  • Demyelination of nerves

  • Burning, numbness, weakness in extremities