NUR306- Patho, Pharm, Genomics- Diabetes & Endocrine- Lecture 2

What genomics term describes having two identical alleles (e.g., two dominant or two recessive genes) for a trait?

Homozygous

What genomics term describes having two different alleles (e.g., one dominant and one recessive gene) for a trait?

Heterozygous

What genomics term describes having only one single copy of a gene (highly common in male patients with X-linked disorders)?

Hemizygous

Why are male patients hemizygous for genes located on the X chromosome?

Because males have only one X chromosome and one Y chromosome (which lacks the corresponding gene)

What type of hormone communication involves a hormone released into circulation to travel to a distant target organ?

Endocrine communication

What type of hormone communication involves a hormone released to act on neighboring cells in the immediate vicinity?

Paracrine communication

What type of hormone communication involves a hormone producing a biological action directly on the same cell that released it?

Autocrine communication

What type of hormone communication involves a hormone acting strictly inside the cell that produced it, without ever being secreted?

Intracrine communication

What type of hormone communication involves a hormone produced within a neuron that travels through blood circulation to hit target cells?

Neuroendocrine communication

What are the four main chemical categories of hormones in the body?

1) Amino acids, 2) Peptides/Proteins/Glycoproteins, 3) Steroids, and 4) Fatty acids

What is the physiological difference between a 'free' hormone and a 'protein-bound' hormone in the blood?

Free hormones are active and ready for immediate use, while protein-bound hormones are deactivated and protected from excretion

How does water solubility affect a hormone's half-life and excretion?

Water-soluble hormones circulate freely, have a short half-life, are degraded by enzymes, and are excreted by the kidneys

Why do protein-bound or carrier-bound hormones (like steroids or thyroid hormones) have a longer half-life?

Because the carrier protein acts as a chaperone, shielding the hormone from rapid degradation and kidney filtration

How does negative feedback regulate endocrine glands?

Elevated final active hormone levels signal the hypothalamus and pituitary to stop producing signaling and stimulating hormones

How does positive feedback affect hormone production?

The effects of a hormone stimulate the body to produce even more of that same hormone (e.g., oxytocin in labor)

What is the basic three-step pathway of the hypothalamic-pituitary-target cell axis?

Step 1: Hypothalamus releases signaling hormones ➔ Step 2: Pituitary releases stimulating hormones ➔ Step 3: Target organ releases final active hormones

Which gland acts as the 'Master Gland' and releases releasing hormones like CRH and TRH?

The Hypothalamus

Which lobe of the pituitary gland synthesizes and releases stimulating hormones like ACTH, TSH, FSH, LH, GH, and PRL?

The Anterior Pituitary

Which lobe of the pituitary gland acts as a storage site for Oxytocin and Vasopressin (ADH)?

The Posterior Pituitary

What is the clinical role of Prolactin Inhibiting Hormone (PIH / Dopamine) released by the hypothalamus?

To stop the anterior pituitary from producing prolactin

What hormone is stored in the posterior pituitary and acts as the 'love/birth hormone'?

Oxytocin

What hormone released by the Pars Intermedia of the pituitary gland stimulates melanin production?

Melanocyte Stimulating Hormone (MSH)

If an endocrine problem originates directly within the final target gland itself, what level of dysfunction is this?

Primary dysfunction

If a target gland is normal, but under-producing because it isn't receiving stimulating hormones from the pituitary, what dysfunction level is this?

Secondary dysfunction

If pituitary and target organ hypofunction occurs due to a defect in the hypothalamus, what level of dysfunction is this?

Tertiary dysfunction

What are three common causes of endocrine glandular hypofunction?

1) Atrophy/underdevelopment, 2) Surgical or congenital absence, and 3) Autoimmune destruction

What are two common causes of endocrine glandular hyperfunction?

1) Glandular hyperplasia, and 2) Hormone-producing tumors

What three target cell defects can lead to clinical hormone resistance (hyporesponsiveness)?

1) Receptor defects, 2) Absent secondary messengers inside the cell, or 3) Defective receptor-hormone binding

What specific cell type in the pancreas produces and secretes insulin?

Pancreatic Beta cells (located within the Islets of Langerhans)

What is the primary etiology of Type 1 Diabetes Mellitus?

Autoimmune-mediated destruction of pancreatic Beta cells, leading to an absolute loss of insulin production

Why is Type 1 Diabetes classified as a catabolic disorder?

Without insulin, the body breaks down fat and protein stores for energy, making the patient highly prone to ketosis

What major genetic complex is strongly associated with the risk of developing Type 1 Diabetes?

The HLA (Human Leukocyte Antigen) gene complex on chromosome 6

What environmental factors can trigger autoimmune beta-cell destruction in genetically predisposed individuals?

Viral infections (e.g., Coxsackie B4, mumps, rubella)

Are obesity and a sedentary lifestyle considered contributory factors in the development of Type 1 Diabetes?

No, obesity and lifestyle factors are completely noncontributory in Type 1 Diabetes

What is the primary pathophysiological defect in Type 2 Diabetes Mellitus?

Presence of hyperglycemia due to insulin resistance combined with a relative insulin deficiency

What is the most common predisposing risk factor for Type 2 Diabetes in the United States?

Obesity (specifically central obesity)

Does Type 2 Diabetes involve autoimmune destruction of pancreatic beta cells?

No, there is no autoimmune destruction; beta-cell failure occurs later due to chronic exhaustion/overwork

What are the classic '3 P's' of diabetes, and what is the starred nursing note regarding them?

Polyuria, Polydipsia, and Polyphagia ➔ Starred Note: These are the 'most common signs of diabetes'

What is the underlying physiological mechanism behind polyuria in diabetic patients?

Hyperglycemia exceeds the renal threshold, spilling glucose into the urine, which forces osmotic diuresis

What is the underlying physiological mechanism behind polydipsia in diabetic patients?

Osmotic diuresis causes severe intracellular dehydration and fluid loss, triggering the brain's thirst center

What is the underlying physiological mechanism behind polyphagia in diabetic patients?

Glucose cannot enter cells without insulin, resulting in cellular starvation and a constant trigger of hunger

Why does diabetes mellitus lead to poor wound healing and slow-healing cuts?

Impaired microvascular circulation and a compromised immune response secondary to chronic high blood glucose

Why do diabetic patients experience a higher frequency of bacterial and yeast infections?

High blood glucose levels feed microbes, and high sugars impair white blood cell function

What is Metabolic Syndrome (Syndrome X)?

A group of co-occurring medical risk factors that severely increase a patient's risk of developing Type 2 Diabetes and cardiovascular disease

What is the waistline measurement criteria for Metabolic Syndrome?

40 inches or more for men, and 35 inches or more for women

What blood pressure criteria determines a risk factor for Metabolic Syndrome?

A reading of 130/85 mm Hg or higher, or actively taking antihypertensive medication

What fasting blood sugar level is considered a risk factor for Metabolic Syndrome?

A fasting glucose of 100 mg/dL or higher, or actively taking diabetes medication

What triglyceride level determines a risk factor for Metabolic Syndrome?

A blood fat level of 150 mg/dL or higher, or actively taking triglyceride-lowering medication

What HDL cholesterol level is a risk factor for Metabolic Syndrome?

Good cholesterol below 40 mg/dL for men, or below 50 mg/dL for women

What is Gestational Diabetes, and when does it typically present?

Diabetes diagnosed during pregnancy, typically onsetting during the second or third trimester

What are the clinical characteristics of Maturity-Onset Diabetes of the Young (MODY)?

A single-gene (monogenic), autosomal dominant inherited disorder causing hyperglycemia before age 25

Which MODY types are most common, and how are MODY 1 and 3 clinically managed?

MODY 1, 2, and 3 are most common ➔ MODY 1 & 3 are managed primarily with oral sulfonylureas

Why does GCK-MODY (Type 2) usually require no pharmacological treatment, except during pregnancy?

Because it remains stable on its own, but poses high neonatal risk during pregnancy

Which MODY type is highly dangerous, requires insulin, and carries a high risk for kidney and organ damage?

MODY 5

How do Metformin transporter genes (SLC genes) affect a patient's diabetes treatment?

Mutations in SLC genes produce difficulty transporting, metabolizing, or eliminating Metformin, causing variable drug efficacy

What causes some diabetic patients to have highly variable therapeutic responses to Sulfonylurea medications?

Single-gene mutations affecting the potassium channels on pancreatic beta cells, or chronic long-term drug use

Under what three clinical conditions should genetic testing for MODY be strongly suspected?

1) A young, non-obese patient diagnosed under age 25, 2) A strong family history of diabetes, and 3) A limited response to standard oral meds

What are the three main metabolic dysfunctions that characterize Diabetic Ketoacidosis (DKA)?

1) Severe Hyperglycemia, 2) Ketosis, and 3) Metabolic Acidosis

What causes the phenomenon of pseudo hyponatremia during a DKA crisis?

An osmotic shift of fluid from inside to outside of cells in an attempt to dilute/normalize high extracellular glucose

What are the typical blood glucose ranges seen in a patient with DKA?

Consistently between 300 mg/dL and 800 mg/dL (though patients can occasionally present as Euglycemic)

Why does a patient in DKA develop fruity or sweet-smelling breath?

Due to the pulmonary excretion of volatile ketones (acetone) from rapid fat breakdown

What is the respiratory compensation mechanism for metabolic acidosis in DKA, and what is its clinical name?

Kussmaul respirations (deep, rapid breathing to blow off carbon dioxide and raise pH)

What are the three major pillars of DKA clinical treatment?

1) IV Insulin infusion, 2) Aggressive hydration, and 3) Potassium/electrolyte replacement

Why is potassium monitoring and replacement critical during DKA insulin therapy?

Insulin forces potassium back into cells, which can drop serum potassium levels to dangerously low levels (hypokalemia)

What are the three main characteristics of Hyperglycemic Hyperosmolar State (HHS)?

1) Extreme Hyperglycemia, 2) High Hyperosmolarity, and 3) Severe Dehydration

Why is there an absence of ketoacidosis in HHS compared to DKA?

The presence of a partial insulin deficiency provides enough insulin to prevent lipolysis and ketone formation, but not enough to control blood glucose

Why is dehydration significantly more severe in HHS than in DKA?

Extreme hyperglycemia causes massive renal osmotic diuresis, pulling large volumes of water from brain and body cells

What neurologic alterations commonly present in HHS, and what condition do they mimic?

Seizures, hemiparesis (partial paralysis), and coma ➔ These cues strongly mimic an acute Stroke

What are the typical blood glucose levels seen in HHS?

Usually exceeds 600 mg/dL, and frequently spikes to more than 1000 mg/dL

What is the absolute number one priority in HHS treatment, and what is the starred warning?

HYDRATION ➔ Starred Note: Correcting glucose/fluid balance too fast can cause severe cerebral edema (irreversible neuro damage)

What autonomic nervous system signs present during rapid-onset hypoglycemia?

Anxiety, tachycardia, sweating, and cool, clammy skin (parasympathetic/sympathetic activation)

What brain function signs present during hypoglycemia as glucose levels drop in the central nervous system?

Headache, difficulty thinking, confusion, altered behavior, seizures, and coma

What are the three standard clinical treatments used to rapidly correct severe hypoglycemia?

1) D50 (IV Dextrose 50%), 2) Glucagon (IM/SubQ), or 3) Immediate oral fast-acting sugars (if patient is awake and can swallow)

What is the Somogyi Effect?

A rebound morning hyperglycemia triggered by unrecognized hypoglycemia during the night (around 2 AM)

Which stress hormones are released during a Somogyi night drop to cause rebound high blood sugars?

Cortisol, glucagon, and growth hormone (which induce transient insulin resistance)

What is the Dawn Phenomenon, and how is it clinically distinguished from the Somogyi Effect?

Morning hyperglycemia caused by circadian spikes in GH and glucagon ➔ Unlike Somogyi, the Dawn Phenomenon is NOT triggered by nighttime hypoglycemia

What is the first-line oral drug class for Type 2 Diabetes, and what is the representative medication?

Biguanides ➔ Metformin (Glucophage)

What is Metformin's primary mechanism of action?

Inhibits glucose production in the liver, sensitizes insulin receptors in tissues to increase glucose uptake, and reduces glucose absorption in the gut

Does Metformin cause hypoglycemia when used as monotherapy?

No, Metformin does not stimulate insulin secretion, so it has a very low risk of causing hypoglycemia on its own

What is the rare but extremely dangerous toxic adverse reaction associated with Metformin?

Lactic Acidosis

What is the starred professor red-text contraindication for Metformin based on renal function?

Contraindicated if eGFR < 30 mL/min (never give)

What is the starred clinical rule for Metformin and patients scheduled for IV contrast dye tests?

Hold Metformin 24-48 hours before giving IV contrast dye, and do not resume for 48 hours to prevent kidney failure and lactic acidosis

Can Metformin Extended-Release (XR) tablets be crushed or chewed?

No! Immediate-release tablets can be crushed, but DO NOT crush or chew extended-release tablets

What is the representative SGLT2 Inhibitor medication, and what is its mechanism of action?

Empagliflozin (Jardiance) ➔ Inhibits SGLT-2 proteins in the kidneys to block glucose reabsorption, promoting glucose excretion in the urine

What are the two major localized infection risks associated with Empagliflozin, and what is your orange handwritten note about it?

UTIs and genital fungal/yeast infections ➔ Orange Note: Peeing sugar ➔ higher risk for infection/UTI

What is the representative DPP-4 Inhibitor ('Gliptin') medication, and what is its mechanism of action?

Sitagliptin (Januvia) ➔ Blocks the DPP-4 enzyme to enhance incretin activity, which increases insulin release and reduces glucagon release after meals

What is the rare but severe adverse reaction of Sitagliptin, and what symptom must the nurse immediately monitor and act on?

Pancreatitis ➔ Monitor for severe, persistent abdominal pain; stop the drug immediately if it occurs

What is the representative Sulfonylurea medication, and what is its mechanism of action?

Glipizide (Glucotrol) ➔ Promotes active insulin secretion from the pancreatic beta cells

What are the two primary adverse effects of Glipizide?

Hypoglycemia and weight gain

What is the starred orange handwritten nursing rule regarding the administration of Glipizide?

Make sure the patient eats with the medication (always take with food to prevent severe hypoglycemia)

What is the representative Thiazolidinedione ('Glitazone') medication, and what is its mechanism of action?

Pioglitazone (Actos) ➔ Activates PPAR-gamma genes to decrease insulin resistance in tissues and decrease hepatic glucose output

What is the major cardiovascular risk and Black Box warning associated with Pioglitazone?

Heart Failure risk due to increased renal fluid retention (contraindicated in patients with active heart failure)

What two unique side effects must female patients be educated on before starting Pioglitazone?

Increased risk of bone fractures and increased ovulation (which can lead to unintended pregnancies)

What is the representative Meglitinide medication, and what is its administration rule?

Repaglinide (Prandin) ➔ Take with the first bite of each meal; skip the dose if the meal is skipped

What is the representative Alpha-Glucosidase Inhibitor medication, and what is its mechanism of action?

Acarbose (Precose) ➔ Inhibits digestive enzymes in the small intestine to delay carbohydrate breakdown and absorption

When must a patient take Acarbose, and what are its most common side effects?

Must be taken with the first bite of each main meal ➔ Common side effects: flatulence, cramps, borborygmus (loud rumbling sounds), and diarrhea

What is the representative GLP-1 Agonist injectable, and what is its mechanism of action?

Semaglutide (Ozempic) ➔ Slows gastric emptying, stimulates glucose-dependent insulin release, inhibits glucagon, and suppresses appetite

What is the high-priority Black Box warning for Semaglutide?

Increased risk of C-cell thyroid cancers (contraindicated if personal/family history of Medullary Thyroid Cancer or MENS 2)

What is the representative dual GLP-1 and GIP-1 Agonist injectable?

Tirzepatide (Mounjaro)

What is the only insulin formulation that is approved for IV infusion, and what is the professor's red-text warning?

Regular Insulin (Humulin-R) ➔ Red-Text Warning: Regular Insulin is the ONLY formulation approved for IV infusion