Genetics and Endocrine Exam Study Guide

Karyotype

• Image of a complete set of an individual's chromosomes.
• Snapshot of chromosomes at a specific point in time.
• Isolating, staining, and examining chromosomes under a microscope.
• Looking at size, shape, and number of chromosomes.
• Helpful for identifying trisomies or monosomies (Down syndrome, Klinefelter's (XXY), Turner syndrome (single X)).

Gene vs. Allele

• Gene: Unit of DNA that transmits genetic information.
• Allele: Different form of a gene.
• Example: If the gene is eye color, alleles can be brown, green, etc.
• One allele is inherited from each parent.

Genotype vs. Phenotype

• Genotype: Set of alleles present; the genetic makeup (e.g., big C big C, big C little C).
• Can be heterozygous or homozygous.
• Phenotype: Appearance; what the genotype looks like (observable physical traits).
• Example: Eye color, stature.

Single vs. Polygenetic Gene Traits

• Single Gene Traits: Only one gene mutation results in a change.
  • Only two possible phenotypes.
  • Can be autosomal or sex-linked.
• Polygenetic/Multifactorial Gene Disorders: Multiple genes and environmental factors involved.
  • More difficult to predict outcomes.
  • Examples: Height, mental health.

Nondisjunction Errors

• Error in meiosis where genetic material isn't appropriately divided.
• Results in extra or missing genetic material.
• Examples:
  • Klinefelter syndrome (XXY): Two X chromosomes don't split during meiosis, individual gets 2 X's from their mother and 1 Y from their father
  • Turner syndrome (X): Single X from one parent and none from the other.

Klinefelter Syndrome (XXY)

• Always male (due to Y chromosome).
• Generally normal intelligence.
• Relatively tall.
• Poor motor coordination.
• Smaller testicles and penis.
• Infertility issues.
• Delayed or absent puberty.
• Feminization (less body/facial hair, broader hips, gynecomastia).

Turner Syndrome (X)

• Always female (single X, no Y).
• Short webbed neck.
• Low-set ears.
• Heart defects.
• Low thyroid hormones.
• Shield-shaped chest.
• Primordial streaks, infertility, immature ovaries.
• Visualization issues.
• Normal intelligence.
• Nondisjunction error leads to monosomy (XO).

Punnett Squares

• Used with single gene traits.
• Predicts genotype and phenotype.
• Example: Eye color (Big B = brown, little b = blue).
• If both parents are heterozygous (Big B little b), the offspring have:
  • 25% chance of blue eyes (little b little b).
  • 75% chance of brown eyes (Big B Big B, Big B little b).

Inheritance Patterns

• Autosomal Dominant: One dominant allele needed to exhibit the disease.
  • No carriers.
  • Examples: Polycystic kidney disease, Huntington's disease, Marfan syndrome.
• Autosomal Recessive: Two recessive alleles needed to exhibit the disease.
  • Carriers exist (heterozygous individuals).
  • Examples: Cystic fibrosis, sickle cell anemia, Tay-Sachs disease, PKU.
• X-Linked Recessive: Carried on the X chromosome.
  • Females can be carriers if they have one normal X.
  • Males with the affected X will have the disease.
  • Examples: Hemophilia A and B, red-green color blindness.

Teratogens

• Substances causing fetal malformation.
• Fetus most vulnerable during the first trimester (days 15-60).
• Examples:
  • Certain medications
  • Recreational drugs
  • Tobacco
  • Chemicals (mercury in contaminated fish)
  • Alcohol (fetal alcohol syndrome)
  • Infections (TORCH)
  • Radiation
• TORCH Infections:
  • T: Toxoplasmosis (cats)
  • O: Other diseases (syphilis, parvovirus, varicella-zoster, listeria)
  • R: Rubella
  • C: Cytomegalovirus (CMV)
  • H: Herpes simplex virus 2

Punnett Square Practice

• Autosomal Dominant Example: Marfan Syndrome
  • Egg donor without condition (aa), sperm donor with one defective gene (Aa).
  • 50% chance of offspring having Marfan syndrome.
• Autosomal Recessive Example: Cystic Fibrosis
  • Both egg and sperm donors are carriers (Aa).
  • 25% chance of offspring having cystic fibrosis (little a little a).
  • 50% chance of offspring being carriers (Aa).
• X-Linked Recessive Example: Red-Green Color Blindness
  • Egg donor is a carrier (Big X little x), sperm donor is unaffected (Big XY).
  • 25% chance of offspring having the condition.
  • 25% chance of offspring being a carrier of the condition.

Module 8: Endocrine

Feedback Loops

• Negative Feedback Loop: Hormone increase triggers the body to stop production.

  • Hormone levels increase → production inhibited.
  • Allows body to self-regulate.
  • Examples: Estrogen, cortisol, thyroid hormones.

• Positive Feedback Loop: Body keeps ramping up hormone production until a specific endpoint.

  • Examples:
    • Oxytocin in labor: Uterus contracts more, oxytocin increases until the baby is born.
    • Blood coagulation.

Levels of Endocrine Dysfunction

• Primary: Problem at the organ/gland itself (e.g., Hashimoto's thyroiditis).
• Secondary: Problem at the pituitary gland (e.g., pituitary adenoma secreting excessive TSH).
• Tertiary: Problem at the hypothalamus.

Example

• Pituitary adenoma causing excessive ACTH release. This impacts the cortisol by increasing it.
  • Increased cortisol is going to cause increased corticotropin. It's a secondary problem.

Adrenal Glands

• Stimulated by ACTH.
• Produce:
  • Cortisol (glucocorticoid)
  • Aldosterone (mineralocorticoid)
  • Androgens (sex hormones)
• Adrenal medulla is stimulated by the sympathetic nervous system.
• Steroids regulate:
  • Fat, protein, carbohydrate metabolism.
  • Inflammation.
  • Blood pressure.
  • Blood sugar.
  • Sleep-wake cycle.

Cushing's Syndrome and Disease

• High cortisol levels.
• Weight gain (abdomen, face, neck).
• Hyperglycemia and hypertension.
• Protein breakdown, loss of collagen (stretch marks, weak ligaments, easy bruising).
• Depression.
• Osteoporosis.
• Acne, virilization/feminization.
• Immune system suppression.
• Causes: Pituitary adenomas, adrenal gland tumors, chronic glucocorticoid therapy.

Addison's Disease

• Low steroids, low cortisol, low aldosterone.
• Autoimmune disorder.
• Early symptom: Patches of bronze skin (increased ACTH).
• Changes in body hair distribution.
• Anorexia, weight loss.
• Hypoglycemia and hypotension.
• Nausea and vomiting.
• Addisonian Crisis: Severe low cortisol levels, life-threatening.
  • Caused by abrupt cessation of steroids (after prolonged use).
  • Symptoms: Dehydration, hypotension, hyperkalemia, hyponatremia, hypoglycemia, weakness.

Pheochromocytomas

• Rogue adrenal medulla mass pumping out stress hormones.
• Floods system with catecholamines (epinephrine, norepinephrine).
• Stimulates the sympathetic nervous system.
• Classic triad: Headaches, sweating, rapid heartbeat, surges in blood pressure.

Hypothyroidism

• Low thyroid hormones.
• Most common cause in developed countries: Hashimoto's thyroiditis (autoimmune destruction of the thyroid gland).
• High TRH, high TSH, low T3/T4.
• Crisis: Myxedema coma (severe hypothyroidism leading to confusion and coma).

Hyperthyroidism

• Elevated thyroid hormones.
• Most common cause: Graves' disease (autoimmune antibodies stimulate excessive secretion of hormones).
• Symptoms opposite of hypothyroidism.
• Crisis: Thyrotoxic crisis/thyroid storm (profound excess of thyroid hormone).
  • Symptoms: High fevers, tachycardia, nausea, vomiting, agitation, psychosis, coma, death from heart failure/pulmonary edema.

Goiter

• Enlargement of the thyroid gland.
• Can be caused by hypo- or hyperthyroidism, Graves' disease, Hashimoto's disease.
• Most common cause worldwide: Iodine deficiency.
• In the US, Graves' disease is the most common cause.
• Not related to parathyroid hormone.

Parathyroid Dysfunctions

• Think CALCIUM
• Hypoparathyroidism: Low parathyroid hormone → hypocalcemia.
  • Causes: Trauma, accidental removal during surgery, genetic disorders.
  • Symptoms: Tingling, muscle spasms, cramps, tetany, numbness, seizures, facial twitch, Trousseau's sign.
• Hyperparathyroidism: High parathyroid hormone → hypercalcemia.
  • Cause: Parathyroid adenoma.
  • Symptoms: Kidney stones, nausea/vomiting, poor concentration, neuropathies, osteopenia, painful bones, pathological fractures.

Growth Hormone

• Proportionate Dwarfism: Hyposecretion of growth hormone during childhood.
  • Short stature, but everything is proportional.
• Giantism: Too much growth hormone in children (open growth plates).
  • Very tall, larger hands and feet, endocrine disorders, heart hypertrophy.
• Acromegaly: Hypersecretion of growth hormone after growth plates have closed.
  • Overgrowth of jaw and facial bones, larger hands and feet, bone deformities, cardiac dysfunction, higher rate of insulin resistance/type 2 diabetes.

ADH (Antidiuretic Hormone)

• Diabetes Insipidus: Lack of ADH secretion → dilute urine, thirst, dehydration.
• SIADH (Syndrome of Inappropriate Antidiuretic Hormone): Excessive ADH secretion → hypervolemia, dilute blood (low serum osmolality), less urine (concentrated).

Insulin

• Key that lets glucose into cells.
• Regulates potassium (allows it to move into cells, preventing hyperkalemia).
• Prevents breakdown of fat (which can lead to ketones and diabetic ketoacidosis).

Diabetes Mellitus

• Type 1 Diabetes: Autoimmune destruction of beta cells in the pancreas.
  • Usually in childhood.
  • No insulin production.
  • Crisis: DKA (diabetic ketoacidosis).
• Type 2 Diabetes: Gradual onset, insulin resistance.
  • Beta cells eventually burn out.
  • Crisis: HHS (hyperosmolar hyperglycemic syndrome).
• Differences between DKA and HHS
  • DKA - Type 1 Diabetes, rapid onset, ketones, acidosis, Kussmaul respirations, younger patients, blood glucose often 300-500 mg/dL
  • HHS - Type 2 Diabetes, gradual onset, no ketones, no acidosis, older patients, blood glucose often >600 mg/dL, more severe dehydration

Gestational Diabetes

• Insulin resistance in pregnancy.
• Acts like type 2 diabetes.
• High risk of developing type 2 diabetes in the future.
• Preterm labor, delayed lung development, excess amount of amniotic fluid, higher birth weight (macrosomia).

Complications of Diabetes

• Heart disease, stroke, hypertension, kidney disease, peripheral vascular disease (atherosclerosis, poor circulation, poor sensation/wound healing), neuropathy, retinopathy, foot ulcers/amputations, infections