Pathophysiology Chapters 21 and 34

Adipose Tissue

Functions

➢Insulation

➢Mechanical support

➢Secretes adipokines

➢Immune cell function

➢Energy reserve

•Adipocytes

➢Fat storing cells

White adipose tissue (WAT)

➢Derived from connective tissue

➢Single lipid droplet

➢Stores

•Visceral (central) stores

•Adipocyte hypertrophy

•More hormonally active

•Subcutaneous (peripheral) stores

•Adipogenesis (hyperplasia)

•Healthier expansion of fat tissue

•Higher in females

•Muscle and bone marrow

Brown adipose tissue (BAT)

➢Derived from embryonic myocytes

➢Multiple lipid droplets, rich in mitochondria

➢Generate heat through oxidation of fatty acids and glucose

•Nonshivering thermogenesis

•Neonatal heat generation

•Protects against obesity

Bone marrow adipose tissue (MAT)

➢Found in all bones

➢Increases with obesity and age

•Beige adipose tissue

➢Found in WAT, multiple mitochondria like BAT

➢Emerge with chronic exposure to cold or exercise

•“Beiging” or “Browning” of WAT

➢Diminished in obesity

Adipose Tissue as an Endocrine Organ

•Adipocytes secrete adipokines

•Adipokines

➢Cell signaling proteins

➢Function like hormones

•Excess WAT causes dysregulation of secretion and function of adipokines

•BAT

➢Releases batokines

Regulation of Food Intake and Energy Balance

•Controlled by central and peripheral physiological signals

•Arcuate nucleus in the hypothalamus balances opposing effects of neurons

➢Orexigenic neurons: promote appetite, stimulate eating, decrease metabolism

➢Anorexigenic neurons: suppress appetite, inhibit eating, increase metabolism

•GI tract secretes hormones that control hunger and satiety

Obesity

•An increase in body adipose tissue

➢Body mass index greater than 30 kg/m2 for adults

➢Greater than the 95th percentile on growth charts for children

•Develops when caloric intake exceeds caloric expenditure in genetically susceptible people

•Major cause of death due to:

➢Cardiovascular disease

➢Type 2 diabetes mellitus

➢Cancer

Predisposing factors Of obesity

➢Genotype and gene-environment interactions

•Polygenic defects

•Obesogens

➢Metabolic abnormalities

➢Mental retardation

➢Environmental factors

•Diet

•Physical activity levels

➢Depression and mood disorders

Pathophysiology Of obesity

➢Interaction of peripheral and central pathways and numerous adipokines, hormones, and neurotransmitters

➢Signaling mediators act on hypothalamus and brainstem to regulate hunger and satiety

➢Leptin – decreased appetite

•Leptin resistance

➢Adipocytokines: Leptin, Adiponectin, Resistin, Visfatin

➢Proinflammatory cytokines: Tumor necrosis factor-alpha, Interleukin-6, -8, and -10, Monocyte chemotactic protein-1, Plasminogen activator inhibitor-1, Retinol-binding protein 4,

➢Other hormones: Insulin, Amylin, Endocannabinoids, Angiotensinogen, Ghrelin, Glucagon-like peptide 1, Peptide YY, Gastric inhibitory peptide

Obesity Produces state of…

chronic, low-grade inflammation in WAT

➢Insulin resistance

➢Metabolic syndrome

➢Other complications

•Alterations in intestinal microbiome

➢May have a causal role in obesity

•Weight loss (bariatric) surgery is the most effective treatment for decreasing obesity-related morbidity  

Lipotoxicity

➢Insulin resistance

•Reduced lipolysis

•Dyslipidemia

•Inflammation

➢Chronic, low-grade

➢Oxidative stress

•Gut microbiome

Visceral obesity

➢Distribution of body fat is localized around the abdomen and upper body

➢“Apple shape”

➢Associated with more obesity complications than peripheral

Peripheral obesity

➢Distribution of body fat is extraperitoneal and distributed around the thighs and buttocks

➢“Pear shape”

Starvation

•Decreased energy intake leading to weight loss

•Malnutrition

➢Lack of nourishment from inadequate amounts of calories, protein, vitamins, or minerals

➢Caused by diet, alterations in digestion, or disease

Short-term Starvation

➢Extended fasting, several days of dietary abstinence or deprivation

•Therapeutic: initial rapid weight loss

➢Body responds to protect protein mass

•Glycogenolysis

•Gluconeogenesis

Long-term Starvation

➢Begins after several days of dietary abstinence

•Therapeutic: weight loss in morbidly obese people

•Pathologic: poverty, disease, and anorexia nervosa

➢Causes death from proteolysis

➢Marasmus—protein energy malnutrition

➢Kwashiorkor—protein deprivation with carbohydrate intake

➢Cachexia

➢Refeeding syndrome

Anorexia of Aging

•Decrease in appetite or food intake in older adults

•Aging associated with decreased orexigenic signals and increased anorexigenic signals

•Risk factors

➢Functional impairments

➢Medical and psychiatric conditions

➢Loneliness and grief; social isolation

➢Abuse or neglect

•Undernutrition leads to adverse outcomes

➢Malnutrition

➢Frailty

➢Mitochondrial dysfunction

➢Reduced regenerative capacity

➢Increased oxidative stress

➢Imbalanced hormones

•Treatment is supportive

DEVELOPMENT OF THE REPRODUCTIVE SYSTEMS

•Dependent on sex hormones

•Males: testosterone

•Females: absence of testosterone, presence of estrogen, FSH, and LH

•Sexual differentiation in utero

•Embryos have homologous structures

•Gonads

•Ducts (Wolffian and Müllerian)

•SRY gene

•Expression: male gonadal development

•Absence of expression: female gonadal development

PUBERTY

•Onset of sexual maturation

•Girls 8-9 years of age

•Boys about 11 years of age

•Involves hypothalamic-pituitary-gonadal axis, CNS, and endocrine system

•Thelarche: breast development

•Gonadarche: gonadal maturation

•Adrenarche: increased production of androgens

Female Sex Hormones

•Estrogen

•Estradiol (E2)

•Androgens

•Progesterone

FEMALE REPRODUCTIVE SYSTEM: MENSTRUAL CYCLE

•Menstrual (ovarian) cycle

•Endometrial cycle

•Follicular/proliferative phase

•Luteal/secretory phase

•Ischemic/menstrual phase

Male reproductive system

•External genitalia

•Testes

•Produce gametes and sex hormones

•Inguinal canals

•Tunica vaginalis

•Tunica albuginea

•Seminiferous tubules

•Leydig cells

•Epididymis

•Vas deferens

Perimenopause

•Ovarian, uterine, and systemic changes

•Vasomotor flush

Menopause

•Breast tissue, urogenital, skeletal, and cardiac changes

•Vasomotor flush

AGING AND THE MALE REPRODUCTIVE SYSTEM

•The male’s reproductive capacity is longer than the female’s

•There is no event comparable to menopause

•Decreased erectile and ejaculatory function

•Testes atrophy, decrease in weight, and soften

•Decreased levels of testosterone; gonadotropins increase

•Decreased libido