NURS3537 Midterm 1 Study Notes-combined PDF

ENDOCRINE SYSTEM HORMONES - Hormones are chemicals that are considered messengers because they provide a communication system between cells - Different cells can respond differently to the same hormone, and cells can have the same response to different hormones - Hormones are essential...

ENDOCRINE SYSTEM HORMONES - Hormones are chemicals that are considered messengers because they provide a communication system between cells - Different cells can respond differently to the same hormone, and cells can have the same response to different hormones - Hormones are essential because they regulate metabolism, growth and development - Endocrine cells have a slower response in the body, but the effects are long lasting - 2 types of cells: o Paracrine – the hormone targets cells nearby o Autocrine – the hormone targets the cells that it is secreted by (regulating pain, sensation, inflammatory response) - Major types of hormones: o Peptide hormones – made of amino acids (insulin, glucagon, pituitary hormones) o Steroid hormones – derived from lipids (reproductive hormones like testosterone, cortisol, estrogen) o Amine hormones – derived from amino acids (epinephrine) - The anterior pituitary produces trophic hormones (stimulate growth and development in other tissues) o Controlled by the hypothalamus - The posterior pituitary hormones act directly on target tissues o Does not produce the hormones it releases - Hormone Receptors o Hormones bind to the cell membrane or intracellular receptors (only bind to a specific receptor) o Only cells with receptors for the hormone will respond o The response depends on receptor number and affinity ▪ Up-regulation: the number of receptors increases in response to rising hormone levels → the cell becomes more sensitive to the hormone → increased cellular activity ▪ Down-regulation: the number of receptors decreases in response to rising hormone levels → cellular activity is reduced - Hormone Degradation o Destroyed by enzymes at receptor site (epinephrine, dopamine) o Taken up by the cells and destroyed (peptide hormones → insulin, glucagon) o Destroyed in the liver and excreted in bile (steroid hormones → T3 and T4) ALTERATIONS OF THE HYPOTHALAMIC-PITUITARY SYSTEM The pituitary gland has 2 regions: - Posterior pituitary (neurohypophysis) – neural tissue extends from the hypothalamus through the infundibulum into a larger region called the pars nervosa - Anterior pituitary (adenohypophysis) – derived from the epithelial tissue of the embryonic oral cavity HYPOTHALAMTIC HORMONES - Equivalent to gonadotropin releasing hormone: o Zoladex, Vantas, Lupron, Synarel - Initially stimulate FSH and LH with chronic use (castration in males and menopause in women) - Cannot be given orally - Ocreotide o Similar to GH release inhibiting factor (somtostatin) o Use for acromegaly o Useful in vasoactive intestinal peptide tumors o GI bleeds and AIDS o Reduces plasma concentrations of vasoactive intestinal polypeptide o Should not interact with cyclosporin and ciproflaxin DISEASES OF THE POSTERIOR PITUITARY - The hypothalamus is part of the limbic system o The limbic system includes the thalamus, amygdala, hippocampus and cingulate gyrus - The hypothalamus is the location of the thermoregulatory centre → regulates the body’s temperature → water balance, BP regulation, sensations of thirst and hunger - The hypothalamus is connected directly to the pituitary gland - The posterior pituitary (yellow sac) includes neurons which come from the brain o It consists of nervous tissue from the embryonic forebrain - Axons reach the posterior pituitary via the hypophyseal tract o They secrete neuro-hormones stored in axon terminals - When stimulated, the lobe secretes ADH (responsible for control of blood osmolarity) and oxytocin (involved in parturition and milk secretion) o Both substances are produced in the supraoptic and paraventricular nuclei of the hypothalamus → then stored in the pituitary gland ready for release - Oxytocin elevation/deficiencies or ADH elevation/deficiencies are directly related to these neurons → deficiencies are related to adenoma benign tumors - The affects of these elevations or deficiencies will be noticeable either: o If other hormones decrease o If one hormone increases exponentially (cells will become squished and have no space) POSTERIOR PITUITARY HORMONES - DDAVP (desmopressin and vasopressin) – synthetic ADH o Used in neurogenic DI, homeostasis in Von Willebrand’s (platelets don’t clump together → shrinkage of blood vessels tricks platelets into clumping) - Pitocin – oxytocin o Induction of labour, control postpartum bleeding SYNDROME OF INAPPROPRIATE ANTI-DIURETUC HORMONE (SIADH) SECRETION - Excessive production of ADH without negative feedback control → Oxytocin will be lower - Occurs when excessive levels of antidiuretic hormones are produced o Antidiuretic hormones help the kidneys and body conserve the right amount of water o Therefore, SIADH will PREVENT you from urinating - Causes: o Ectopically produced ADH (ADH is being produced where it should not be) ▪ Oat cell carcinoma of the lung (most common cause) ▪ Carcinoma of the duodenum, pancreas, leukemia, Hodgkin’s disease (not common) - Pathophysiology o Excessive levels of ADH act on the kidney tubules ▪ You will see fluid retention (patient will gain excessive water weight) o Relative hyponatremia, hypo-osmolality (electrolytes and proteins in the blood will be lower than normal because there is more water than solutes) ▪ For hyponatremia, you must figure out how many days it took the patient to become hyponatremic, and return the patient to the regular state according to the length of time (e.g., if it took the patient 4 days to become hyponatremic, it should take 4 days for the patient to return to normal) o Cells become hypotonic (swell with fluid and can burst if hyponatremia continues) - Clinical Manifestations – caused by excessive water o Exertional dyspnea (shortness of breath that occurs during physical activity or exercise → BP high, develop pulmonary edema) o Fatigue o Dulled sensorium o Vomiting and abdominal cramps o Muscle twitching, confusion, convulsions - TREATMENT: Give hypertonic saline DIABETES INSPIDOUS (DI) - Insufficiency of ADH secretion (low ADH) → oxytocin will be higher - Causes an imbalance of fluid in the body o Leads to large amount of urine production o Also causes excessive thirst even after drinking water - There is no cure → treatment can relieve the thirst and decrease urine output to prevent dehydration - Causes: o Neurogenic causes (ADH is produced by hypothalamic neurons) ▪ Lesions of the hypothalamus, pituitary stalk or posterior pituitary interferes with ADH synthesis or release Brain tumors, hypophysectomy (removal of pituitary gland), aneurysm of the Circle of Willis, thrombosis, infection o Nephrogenic causes: ▪ Lesions of the kidney tubules (so they are unresponsive to ADH) Pyelonephritis (a type of UTI where one or both kidneys become infected, uropathies (damaged nephrons/blockage), polycystic disease (cysts develop within the kidneys, causing them to enlarge and lose function over time) - Pathophysiology o Lose the ability to concentrate urine → eliminating large volumes or dilute urine o Increased plasma osmolarity (will cause relative hypernatremia) ▪ Opposite of SIADH o May result in circulatory collapse (removing water = removing plasma → less space for cells to move, so they will sit and clot) or hypertonic encephalopathy (neurons will stop working) - Clinical manifestations o Polydipsia, polyuria (often over 12 litres per day), nocturia o Decreased urine specific gravity (just peeing out water) o Signs of dehydration - TREATMENT: give ADH (hormone replacement) DISEASES OF THE ANTERIOR PITUITARY - Releases 6 hormones: o Follicle Stimulating Hormone (FSH) – stimules testes to produce sperm and the ovaries to produce eggs and estrogen o Luteinizing Hormone (LH) – stimulates ovulation in women and testosterone production in men o Adrenocorticotropic Hormone (ACTH) – stimulates adrenal glands to produce cortisol and other hormones → adrenal glands are on the kidneys o Thyroid Stimulating Hormone (TSH) – stimulates thyroid to produce hormones related to metabolism, energy and the nervous system o Growth Hormone (GH) – stimulates growth in children, maintains healthy muscles and bones, impacts fat distribution in adults o Prolactin – stimulates breast milk production, affects menstruation, fertility, sexual function → low testosterone in males and low estrogen in females - All the hormones are synthesized in the anterior pituitary itself - How is secretion controlled? o They are secreted via blood circulation (hypothalamo-hypophysial portal system) o First blood flows through a capillary bed in the hypothalamus o Then it flows into a second capillary bed in the anterior pituitary o Hormones added to the blood are called releasing hormones (RH) and inhibiting hormones (IH) ▪ Each RH and IH have specific actions (e.g., there are separate RH for GH and TSH) ANTERIOR PITUITARY MEDICATIONS - Cortrosyn (IM) – synthetic ACTH used to test for adrenal insufficiency o Travels to the adrenal cortex to stimulate secretion of mineralocorticoid cortisol - Humatrope – for growth failure, Turner’s (girls w/ only 1 X chromosome), renal failure, growth retardation - Chorex (HCG) – for luteinizing hormone, used in men if testes do not descent (cryptorchidism) - Ovidrel (HCG alpha) – used with menotropins to induce ovulation - Pergonal (menotrpoins) – contains FSH and LH - Somavert – GH receptor antagonist (does not accept GH) - Follitish – for FSH used with HCG HYPOPITUITARIANISM - Reduction or absence of pituitary hormones due to infarction (cell death), post partum thrombosis (due to hypercoagulability related to pregnancy) PANHYPOPITUITARIANISM - Any of the anterior pituitary hormones may be absent - Common causes: neoplasms of the pituitary that are large enough to destroy the gland, postpartum pituitary necrosis, or surgical removal of the gland o The pituitary becomes hyperplastic during pregnancy which makes it more susceptible to infarction (Sheehan Syndrome) - Clinical Manifestations: o Low FSH and LH (sex hormones) → gonadal atrophy and failure ▪ Decreased secondary sex characteristics (men will look like women and women will look like men) ▪ Dysmenorrhea/amenorrhea (no period), atrophy of vaginal mucosa, breasts, uterus ▪ Reduced body hair and increased breast size in men ▪ Diminished libido o Low ACTH ▪ Decreased cortisol (brain) – hypoglycemia, weakness, fatigue, N/V, lack of immune regulation ▪ Decreased androgens – loss of body hair (men), lower libido o Low TSH → low T3 and T4 → decreased basal metabolic rate ▪ Lethargy, weight gain, dry skin, myxedema, cold intolerance, bradycardia, difficulty breathing o Low GH → causes pituitary dwarfism in childhood ▪ Can be congenital (born with it) or acquired ▪ Need to fix before epiphyseal plate is capped o Low Prolactin ▪ Less lactation in post-partum women - Can be treated by dietary replacement of trophic hormones - **Melanocyte stimulating hormone (MSH) is a group of peptide hormones produced by the skin, pituitary gland and hypothalamus. Its production is enhanced in response to UV light and it plays a role in producing pigment in hair, skin and eyes HYPERPITUITARISM - Causes o Adenomas of pituitary tissues → increased secretion from the cells from which they arise, but compression and lower secretion from other cells (e.g., increased GH = decreased FSH, LH, ACTH, TSH) - Gigantism – occurs in CHILDREN with increased GH, and occurs before epiphyseal plate is developed o The hypothalamus secretes GHRH (growth hormone releasing hormone) to stimulate the anterior pituitary to secrete more GH ▪ Secretion is stimulated by hypoglycemia, fasting, starvation and stress ▪ The opposite of this is GHIH (Somatostatin) to inhibit GH secretion Stimulated by increased glucose, free fatty acid release, obesity, cortisol o Results in unusual height (7-9 feet) and early osteoarthritis - Acromegaly (occurs AFTER PUBERTY) o Body produces too much GH and causes bones and body tissues to grow quickly o Any person can develop acromegaly if a tumor is present in the pituitary gland o The hypothalamus secretes GHRH (growth hormone releasing hormone) to stimulate the anterior pituitary to secrete more GH ▪ Secretion is stimulated by hypoglycemia, fasting, starvation and stress ▪ The opposite of this is GHIH (Somatostatin) to inhibit GH secretion Stimulated by increased glucose, free fatty acid release, obesity, cortisol o The person will experience pain due to bones rubbing together; osteoplasts will fuse bones together o Causes: GH secreting adenomas → increased GH and IGF-1 (insulin like growth factor) levels ▪ Increased GH tells liver to produce IGF-1 → insulin receptors ill decrease → patient will develop Type II diabetes ▪ Slow progressive changes o Pathophysiology: ▪ Increased GH leads to connective tissue proliferation, increased bone mass ▪ Impaired carbohydrate tolerance leads to increased metabolic rate (glucose will float in the blood) ▪ Inhibition of glucose uptake o Clinical manifestations ▪ Arthralgia (joint stiffness), backache due to bony overgrowth and entrapped spinal nerves ▪ Peripheral nerve damage, muscular atrophy, weakness, sensory changes ▪ Increased intercranial pressure → headache, papilledema ▪ Visual disturbances due to interference with optic chiasma ▪ Pressure hypopituitarism can lead to amenorrhea and sterility ALTERATIONS OF THYROID FUNCTION - Thyroid hormone (T3 and T4) is controlled by a negative feedback system that involves the hypothalamus, pituitary gland, thyroid gland and multiple hormones o To begin the feedback loop, the hypothalamus secrets TRH (thyroid releasing hormone) to stimulate the pituitary gland to release TSH o TSH triggers the thyroid to produce T3 and T4 ▪ 80% of hormone released is T4 and 20% is T3 ▪ The body needs to get iodine from food in order to create T3 and T4 o The feedback loop works so when T3 and T4 increase, the release of TRH stops. When T3 and T4 decrease, the loop starts again ▪ This allows the maintenance of a constant level of hormone in the body ▪ Issues with the hypothalamus, pituitary gland or thyroid can result in imbalance - T3 (triiodothyronine) and T4 (thyroxine) are referred to as the “thyroid hormone” o T4 is inactive (does not impact the cells) but T3 is active o When the thyroid gland releases T4, the body converts it into T3 so it can have impact on the cells and metabolism - The thyroid is two glands that are connected and are located in the front of the neck, lateral to the trachea o It is consisting of acini, which secretes a colloid substance that contains the hormones - Idiopathic hypothyroidism, Hashimoto thyroiditis, Graves disease, nodular goiter, adenoma and papillary carcinoma are the most common diseases affecting the thyroid gland HYPERTHYROIDISM (THYROTOXICOSIS) - Excessive T3 and T4 secretion - Causes: o Graves disease (most common for 70-80% of cases) o Thyroid adenoma, toxic multinodular goiter, - Grave’s Disease o Caused by the stimulation of the thyroid by an antibody (Thyroid Stimulating Immunoglobulin) that mimics TSH o Even though TSH may be suppressed due to increased hormone levels, the thyroid can be enlarged and infiltrated by lymphocytes - Clinical Manifestations o Thyroid enlargement (goiter) o Increased T3 and T4 leads to increased metabolic rate o Heat intolerance, skin flushing, sweating, temperature over 40 o Increased GI motility (weight loss despite increased appetite, loose stool) o Expenditure of minerals (fatigue) o Increase in metabolic rate of neurons (nervousness, tremors) o Increase in metabolic rate of cardiac muscle cells (tachycardia, dysrhythmias, hypertension, palpations) o Muscle degeneration (thyrotoxic myopathy) o Bone fractures o Ocular changes (exophthalmos/bulging eyes), weakness of eye muscles o Onycholysis – rapid nail growth way from the skin - Diagnosis o Measurement of thyroid hormone and TSH in the blood - Treatment o Radioactive iodine therapy – can destroy the thyroid gland and cells that take up iodine without affecting other cells o Remove thyroid o Medication (methimazole) → strict adherence o Avoid food with high iodine - Thyroid storm o Occurs as a result of untreated hyperthyroidism o Body enters overdrive because of too many thyroid hormones o Extreme tachycardia, high blood pressure, fever HYPOTHYROIDISM - Low amount of thyroid hormone - Causes (in adulthood): o Iodine deficiency o Acute thyroiditis (bacterial infection) o Sub-acute thyroiditis (viral infection) o Auto-immune thyroiditis (Hashimoto’s thyroiditis) ▪ Lymphocytes gradually destroy the epithelial cells in the thyroid ▪ They are primed to attack the thyroid by antibodies that are generated against thyroidal agents such as thyroglobulin and thyroid peroxidase (proteins used in hormone synthesis) ▪ Lymphocytes flood the thyroid and make aggregates ▪ The thyroid will begin to enlarge symmetrically, but over time it will be replaced by fibrosis and you will begin to see symptoms o Thyroid ablation - Clinical Manifestations (in adulthood) - Lethargy - Tongue enlargement - Cold intolerance - Non-pitting edema - Easily breakable and brittle hairs - Slow muscular responses (speech and reflexes) - Bradycardia - Weigjht gain - Prolonged: deposits of mucopolysaccharides in the - Sallow complexion skin, muscle and viscera, myxedema - Congenital hypothyroidism o Thyroid dysgenesis (thyroid is missing, ectopic or severely underdeveloped) o Hereditary defects of TH synthesis - Causes (Congenital) - Intellectual mal development - Myxedema causing a protruded tongue → difficulty - Reduced skeletal growth feeding - Lethargy, bradycardia, cold intolerance - Abnormal protrusion, umbilical hernia - Hypothermia - Jaundice - Treatment: administration of synthetic T3 and T4 - **Cretinism – severe deficiency in newborns left untreated - Patients with hypothyroidism after thyroidectomy will have a low basal metabolic rate - Thyroid storm can be precipitated by the stress of thyroidectomy, anesthesia or thyroid manipulation ALTERATIONS OF PARATHYROID FUNCTION - The parathyroid glands are two pairs of small glands located next to the thyroid lobes (each gland is about the size of a pea) - Parathyroid glands secrete parathyroid hormone (PTH) o PTH regulates the balance of calcium and phosphate in the blood o Stimulates the release of calcium from bone o Increases renal absorption of calcium o Enhancing calcium absorption in the GI tract o Stimulate activation of Vitamin D in the kidneys o Inhibits renal absorption of phosphorus - If a patient’s calcium is low, administer PTH HYPERPARATHYROIDISM - Parathyroid glands create excess PTH in the bloodstream o Leads to increased calcium reabsorption - Condition can go undetected for a very long time - Causes: o Primary → adenomas (can grow in a single parathyroid gland), diffuse hyperplasia of all 4 glands, carcinoma o Secondary → chronic renal failure (lose calcium through the kidneys, so PTH increases), vitamin D deficiency o Tertiary → PTH is still produced even after serum calcium is regulated (chronic) - Pathophysiology: o Due to adenomas ▪ Secretion of excessive PTH without feedback control ▪ Kidneys increase vitamin D synthesis in response to excessive PTH increased GI absorption of calcium ▪ Hypercalcemia + hypophosphatemia – calcium and phosphorus are reversely proportional to each other Phosphate is a main ingredient in ATP. So low phosphorus can cause muscle weakness and fatigue Loose phosphate in the urine Increased calcium causes calcium stones in the kidneys Calcium deposits in the pancreas can lead to insulin resistance ▪ Increased osteoclastic activity → osteoporosis, pathologic fractures, kyphosis, vertebral compression o Due to renal failure ▪ Decreased renal function causes low vitamin D and decreased absorption of calcium in the GI tract ▪ Hypocalcaemia – increased PTH levels but calcium remains low due to kidney failure - Clinical Manifestations o Kidney stones o Fragile bones o Fatigue o Headache o Anorexia o Nausea (hypercalcemia increases gastrin production) and vomiting o Excessive urine o **Stones, Bones, Groans, Thrones, and Psychiatric Overtones - Treatment depends on underlying cause HYPOPARATHYROIDISM - Body produces low PTH - Very uncommon because all 4 glands have to be removed or destroyed - Main complications are not caused by bone mineralization, but rather by the effect of low calcium in the blood - Pathophysiology o Hypocalcaemia, hyperphosphatemia ▪ Decreased magnesium can lead to hypocalcaemia o Hypersensitivity of neurons - Clinical Manifestations o Tetany (carpo-pedal spasm) → prolonged contraction of the muscle after a single stimulus o Paresthesia (tingling sensation) o Hyperreflexia o Convulsions o Abdominal cramps o Urinary frequency o Dyspnea, laryngeal spasms, death by asphyxiation ALTERATIONS OF ADERNAL FUNCTION - The adrenal glands are located within the abdomen, embedded in adipose tissue superior to each kidney - The glands are composed to two distinct tissues: o Cortex – epithelial cells that synthesize and create glucocorticoids, mineralocorticoids and androgens o Medulla – chromaffin cells secrete hormones involved in the vascular system (epinepherine/adrenaline HYPERCORTISOLISM – CUSHING SYNDROME/DISEASE - Cushing Disease – hypercortisolism with pituitary involvement o Excess ACTH = excess cortisol o E.g., pituitary adenoma - Cushing syndrome – hypercostirolsm with or without pituitary involvement o Iatrogenic form of cortisol being used (exogenous steroids) → Prednisone o Chronic asthma, arthritis, lupus, psoriasis because of medication overuse - Causes: o ACTH stimulated hypercortisolism (ACTH AND CORTISOL ARE HIGH) ▪ Dysfunction of the hypothalamus-pituitary system (adenoma) ▪ Ectopic ACTH production (oat cell carcinoma) ▪ Manifestations: Hirsutism (excessive hair growth in women) due to androgens Hyperpigmentation due to MSH Impotence, dysmenorrhea/amenorrhea (due to decreased production of FSH and LH) o Non-ACTH stimulated hypercortisolism (ONLY CORTISOL IS HIGH) ▪ Tumor of the zona fasciculata ▪ Exogenous steroid use ▪ **will not see increased melanin (MSH not involved) - Clinical Manifestations o Central obesity limited to face, trunk and upper back (moon face, buffalo hump) but arms and legs are still thin o Proximal muscle weakness, fragile skin (breaks and bruises → osteoporosis) o Striae of the skin on the abdomen and breasts o Diabetes due to inhibited glucose absorption o Spots on the face, chest, and shoulder (can be infected due to immunosuppression) o Hypertension (vasoconstriction due to steroids) o Growth disturbances in children o Depression, psychosis o Urinary frequency (third due to hypertonia) HYPOCORTISOLISM – ADDISON’S DISEASE - Reduced cortisol levels due to: o Inadequate ACTH o Dysfunction of the adrenal cortex → autoimmunity (Addison’s disease) o Taking patients off their steroidal medication suddenly without tapering it down o Can also be caused by tuberculosis - Pathophysiology – Primary Hypocortisolism (Addison’s Disease) o Autoimmunity leads to adrenal atrophy and decreased adrenal cortical function (damaged adrenal glands) o Decreased cortisol and aldosterone levels, increased serum ACTH o Acute insufficiency can be caused by either stress or infection (immediate treatment with glucocorticoids and electrolytes) o Generally treated with replacement of corticosteroids, mineralocorticoids and androgens - Clinical Manifestations of Addison’s Disease o Weakness and fatigue due to hypoglycemia or hypotension o Decreased aldosterone leads to hyponatremia, dehydration, hyperkalemia o Hyperpigmentation due to increased ACTH (precursor of ACTH is the same for MSH) o Nonspecific symptoms (N/V, fatigue, diarrhea) - Pathophysiology (Secondary hypocortisolism) o Negative feedback is lost due to: ▪ Cortisol secreting tumors ▪ Cortisol is administered therapeutically ▪ Cortisol levels increase, ACTH decreases → leads to adrenal atrophy o Clinical manifestations are the same as Addison’s disease MINUS hyperpigmentation (ACTH and MSH are low) o Treated with administration of cortisol - TREATMENT: Hydrocortisone and Cortisone HYPER-ALDOSTERONISM - Excessive aldosterone secretion - Causes: o Adenoma of the zona glomerulosa o Increased angiotensin (can be due to kidney failure) o Hyperkalemia - Clinical manifestations o Renal sodium and water reabsorption can lead to hypernatremia and hypervolemia (excess fluid in the blood) ▪ Hypertension, left ventricular hypertrophy ▪ Hypokalemia, alkalosis ▪ Electrolyte imbalances (neuromuscular disorders, dysrhythmias) angiotensin, K+ ACTH zona glomerulosa aldosterone zona fasciculata cortex cortisol zona reticularis medulla androgens ’ HYPERSECTION OF ALDOSTERONES AND ESTROGENS - Can be due to tumors of the zona reticularis, or Cushing syndrome - Clinical Manifestations depends on which cells are at fault o Tumors of estrogen producing cells ▪ Leads to feminization in males Gynecomastia Testicular atrophy Decreased drive o Tumors of androgen producing cells ▪ Leads to masculinization in females Hirsutism Clitoral enlargement Deepening of the voice Breast atrophy Acne Alopecia Amenorrhea DISORDERS OF THE ADRENAL MEDULLA – PHEO CHROMOCYTOSIS - Neoplasm of the cells that produce catecholamines in an unregulated fashion o Epinephrine and norepinephrine o Continually elevated catecholamines increase vascular tone (leads to hypertension and heart failure) o Periodic bursts of hormones related from the tumors give patients headache, flushing, sweating, palpations, anxiety and tremors - Clinical Manifestations o Tachycardia o Hypertension o Flushing and heat intolerance o Diaphoresis (excessive sweating) o Headache o Hyperglycemia (due to insulin antagonism) o Weight loss (increased basal metabolic rate) o GI alterations - Diagnostic Tests o Blood tests can detect hormones, antibodies and regulated substances (such as blood glucose) o Urine test ▪ Vanillylmandelic acid (VMA) is a catecholamine breakdown product → can be measured for diagnosis (it will be elevated due to increased catecholamines) o Stimulation test to diagnose hypofunction (glucagon) o Suppression test to diagnose hyperfunction (clonidine) o Genetic testing o Imaging studies – isotopic imaging, MRI, CT, ultrasound, PET, DEXA - The patient’s blood pressure has to be aggressively treated prior and during surgery because a sudden release of catecholamines can result in lethal hypertension - Treatment involves hormone therapy, symptom management and partial or complete ablation CORTICOSTEROIDS - Endogenous corticosteroids are made by the body itself. Exogenous corticosteroids are artificial ENDOGENOUS CORTICOSTEROIDS - Steroid hormones are collectively called corticosteroids and they are synthesized from cholesterol - They are produced on demand by the adrenal cortex in response to stimuli (e.g., low plasma levels of steroids, pain, anxiety, trauma, illness, anesthesia) - They are bound to lipids in the plasma - They are metabolized by the liver and excreted in bile or urine - Negative feedback system: hypothalamus (CRF)→ anterior pituitary (ACTH) → adrenal cortex (glucocorticoids) - Glucocorticoids – activate immune system o cortisol is the main glucocorticoid (as well as corticosterone and cortisone) o 15-20 mg of glucocorticoids are secreted daily o Secretion is cyclical → large amount produced in the morning, small amount in the evening ▪ The rhythm is affected by stress - Mineralocorticoids – regulate blood volume and pressure o Aldosterone is the main and most potent hormone - Gonadocorticoids – sex hormones o Most are weak androgens which are converted to testosterone/estrogen - Role of Endogenous Corticosteroids CVS: regulates CNS: reduce nerve MSK: reduce bone Resp: keeps Inflammatory: GI: decrease arterial BP by excitability and formation and airways open stabilize mast cells gastric mucus modifying smooth slow activity increase bone and other cells to (stomach muscle tone breakdown inhibt release of protection from inflammatory peptic ulcers) substances EXOGENOUS CORTICOSTEROIDS INDICATIONS FOR USE - Any illness with an inflammatory or immunologic component (allergies, collagen disorders, endocrine disorders, asthma, COPD, arthritis SYSTEMIC CORTICOSTEROIDS - Betamethasone and Dexamethasone (oral and parenteral) o Prevents respiratory distress syndrome in premature infants (administered 48-72 hours) o Preferred for cerebral edema because it crosses the blood brain barrier and reaches high concentrations in the CSF (brain tumor, neurosurgery, meningitis) → Dexamethasone - Hydrocortisone and Cortisone – requires replacement of glucocorticoids and mineralocorticoids - Prednisone – allergy, stress, immunosuppressive therapy - Methylprednisolone, hydrocortisone, dexamethasone – anaphylaxis and spinal shock (acute life saving situation) ADVERSE EFFECTS OF LONG TERM USE OF SYSTEMIC CORTICOSTEROIDS NURSING ADMINISTRATION - Preferred route of administration is oral - Acute treatment is usually in larger doses over 48-72 hours, and then tapers off as condition improves - Steroid flare from injection o Post injection flare is very similar to an infection (redness, warmth, swelling) o Rest, analgesic and local application of ice will reduce pain CONTRAINDICATIONS - Systemic fungal infection - Hypersensitivity - Use with caution in patients who are at risk for infection, diabetics, patients with peptic ulcers, IBS, CHF, renal insufficiency o Increased monitoring NURSING ASSESSMENT - Pre-administration: examine activity level, appetite, and weight (patients need to exercise) - Post-administration: signs of infection, weight gain (over 5 lb per week), activity level, appetite, hypertension - CAUTION: Daily administration of 15-20 mg of hydrocortisone or its equivalent for 2 weeks suppresses the HPA axis → MUST TAPER DOWN PATIENT TEACHING - for patients on long term treatment - Increase calcium and vitamin D intake to prevent osteoporosis - Increase protein intake to prevent muscle wasting - Increase vitamin C to prevent excessive bruising - Decrease sodium and increase potassium to prevent hypokalemia - Should carry a medical alter or warning card due to falls risk, and altered response to shock DIABETES MELLITUS - Prevalence of diabetes varies by age and race - Diabetes is a disease where there is a persistent state of hyperglycemia and loss of glucose homeostasis - In order for cells to use glucose, you need insulin (a hormone produced by the beta cells in the pancreatic islets) o In diabetes, the effect of insulin is diminished because of decreased production OR cells become resistant to its affects - Diagnosis o Physical exam and medical history o Ophthalmological examination may show retinopathy o Leb tests such as urinalysis (glucose in urine), fasting blood glucose, insulin level test, oral glucose intolerance test (if you give the patient something sweet to eat, the glucose will not breakdown even after hours) A1C – RBCs are covered with glucose that binds → testing will show that RBCs have lots of glucose on them TYPE ONE DIABETES MELITUS - Causes o Gene (chromone 6) → strongly linked to HLA haplotypes o Environment (rubella, mumps viruses) o Auto-immunity → lymphocytes attack antigens on the beta cells and destroy them ▪ This is why the disease is not clinically apparent until insulin production is diminished y at least 90% - Pathophysiology o Loss of beta cells leads to decreased insulin production and increased alpha cell production of glucagon o Auto antibodies to both islet cells and insulin are normally found o Increased pressure on weakened cells - Usually diagnosed when a child drinks a lot of water and urinates frequently (including nocturia and bed wetting) - Clinical Manifestations – caused by hyperglycemia itself o Polyphagia (frequent eating) o Polydipsia o Polyuria/glucosuria (because cells are hypotonic) o Weight loss and fatigue o Blurred vision o Low potassium (can lead to abnormal ECG) o Ketonuria - Management o Meal planning o Exercise programs o Always need insulin o Matching insulin to carbohydrate o Self monitoring of blood glucose TYPE TWO DIABETES MELLITUS - Less insulin + insulin resistance - Causes o Obesity is strongest risk factor - Pathophysiology o Decreased beta cell responsiveness to serum glucose levels o Insulin resistance because plasma insulin levels may not be decreased o Abnormal alpha cell secretion o Decreased number of insulin receptors o Overeating can lead to chronic hyper insulinism which leads to fewer insulin receptors o Cells do not response to insulin → in response to persistent hyperglycemia, the beta cells increase their insulin production and the islet cells can burn out - Clinical Manifestations o Class symptoms such as polydipsia, polyuria and hyperglycemia may be present o More subtle symptoms such as weight gain, hyper-lipidemia, infections and visual changes can occur o Patients are more likely to develop hyperosmolar nonketoic coma due to severe dehydration - Treatment o Diet o Exercise o Control of stress o Prevent and monitor infections (microorganisms flourish in high serum glucose) o Use of oral hypoglycemic agents o Often the use of insulin therapy will be needed long term COMPLICATIONS OF DIABETES MELLITUS ACUTE COMPLICATION: HYPOGLYCEMIA - Too much insulin, inability to keep up with diet, excessive alcohol intake, delayed or missed meal - Signs and symptoms: tremors, pallor, confusion, tachycardia, hunger, seizure, coma - To raise blood glucose: o If it is very low, the patient needs IV o If it is between 2-3 the patient gets glucagon o If it is between 3-4 the patient needs sweetened orange juice ACUTE COMPLICATION: HYPERGLYCEMIA - Glucose is too high - Signs and symptoms: polyuria, polydipsia, weakness, light-headedness, dehydration, weight loss - May cause hyper-osmolar hyperglycemia state (DKA) → if hyperglycemia is very acute HYPEROSMOLAR HYPERGLYCEMIC STATE/HYPEROSMOLAR NON-KETOIC SYNDROME (HONK/HHS) - Due to inadequate insulin - Serious condition caused by extremely high glucose levels → commonly occurs in people with T2D due to illness or infection - Body tires to rid itself of glucose by passing it in urine o Too much glucose makes it hypertonic and attracts fluid from cells (leads to osmotic diuresis, dehydration, impaired renal function) - Also has to deal with burns, MI, Cushing’s syndrome, GI hemorrhage, sepsis, and people with no intake experiencing N/V - If untreated, you can get life threatening dehydration - Decreased LOC, stupor, coma, seizures, muscle twitching - Profound dehydration (10-15% water weight loss) o Parched lips, poor turgor, dry mucous membranes, sunken eyeballs - Polyuria, polydipsia, hypovolemia - Hypotension, tachycardia, hypo-perfusion - High serum sodium, urea - Glucose 36-266 mmol/L - Management: o Rapid rehydration while maintaining electrolyte homeostasis (check glucose every 15-30 min) o Correct hyperglycemia (provide subc insulin; not all patients need insulin, come need glycemic control) o Treat underlying disease o Monitor and assist cardiovascular, pulmonary, renal and CNS function ACUTE COMPLICATION: DIABETIC KETO ACIDOSIS (DKA) - Due to inadequate insulin (caused by diabetes, infection, stress, etc.) - Fat it metabolized → ketoacidosis - Lethargy, confusion, coma - Glucose is being made by lack of insulin means it is not being used - Management o Treat dehydration first ▪ Give fluid (insulin and electrolytes) ▪ Monitor very closely ▪ If you are adding potassium to the fluid, you must monitor extremely closely (high alert drug) CHRONIC COMPLICATIONS MICROVASCULAR DISEASE: thickening of capillary basement membrane and endothelium (leads to thrombosis and eventually ischemia) - Microangiopathy – disease of small blood vessels in the microcirculation NEUROPATHIES – leading cause of nontraumatic lower extremity amputations - Glycosylation end products and polyols damage neurons - Somatic changes (sensory deficits), neural tissue damage, numbness, tingling, autonomic changes (diarrhea, altered bladder function, delayed gastric emptying, orthostatic hypotension) VISUAL CHANGES – leading cause of blindness in working age adults - Stage I retinopathy; - Stage II: ischemia and infarcts - Stage III: o Vessel dilation o Neo-vascularization and o Increased retinal capillary fibrosis permeability o Retinal detachment o Micro-aneurysms o Macular edema and o Superficial hemorrhages degeneration → leads to o Hard exudate (lipid) blindness accumulation NEPHROPATIES: leading cause of end stage renal disease - Arteriolar sclerosis, glomerular enlargement + basement membrane thickening (glomerulosclerosis), GFR drops and leads to renal failure MACROVASCULAR DISEASE - Hyperlipidemia, HDL levels are now (atherosclerosis of aorta, carotids, cerebral vessels → CVA), peripheral vascular disease (gangrene), coronary artery disease (MI) INFECTION - Due to hypoxia, increased glucose (meets the nutritional needs of pathogens), ischemia (less WBC to tissues), impaired senses lead to increased risk of injury RENAL SYSTEM STRUCTURE AND FUNCTION - The kidneys process approximately 1700L of blood in one day and combine their waste products int about 1.5L of urine Cortex – outer part Medulla – inner part Pyramids – triangular shaped divisions Papilla – narrow tip of the pyramid Calyx – opening into each calyx is the papilla of a pyramid Pelvis – extension of the upper end of the ureter URINARY TRACT OBSTRUCTIONS (OBSTRUCTIVE UROPATHY) - Interference with the flow or urine at any site along the tract → leads to urine backing up - Urine collects proximal to obstruction and can lead to infection and damage to uninvolved organs - Usually acquired due to tumors, stones, trauma, pregnancy, GI tract inflammation, BPH, prostate or uterine cancer - Hydronephrosis: swelling of one or both kidneys (occurs when urine can’t drain from the kidney and builds up - Depends on: o Location – upper or lower o Unilateral (can still produce urine) or bilateral (more acute) o Partial (can still produce urine) or complete (no urine) o Acute (kidney stones, trauma) or chronic (cancer, pregnancy) o Underlying cause o There will always be accumulated fluid proximal to obstruction - Consequences: o Hydroureter – ureter expands due to backup of urine o Hydronephrosis – due to retrograde increase in hydrostatic pressure in renal pelvis and calyces ▪ Obstruction can lead to hypoxia and necrosis ▪ Complications include infection and renal failure o Acute, complete obstruction = increased pressure in proximal tubule, decrease in GFR and renal failure o Chronic, partial obstruction = compression of kidney structures, ischemic atrophy of papillae and medulla (starts at the site of obstruction and move upwards) ▪ Think about electrolyte imbalance, ABG disorder ▪ Kidneys initially get larger and then start to atrophy ▪ Tubule damage can lead to decreased ability to conserve sodium and water, and excrete hydrogen and potassium ▪ Increase in urine output with a low GFR (letting go of nutrients we should be keeping) o Post obstructive (cleared) diuresis = loss of large volume of urine following release of obstruction due to salt, water retention during people of obstruction, and GFR returning to normal - Polycystic Kidney Disease – genetic disorder characterized by the growth of numerous cysts in the kidneys o Many cavities filled with fluid o Can be congenital o Heart has to beat much more in order to get blood through to the kidneys o Not caused by obstruction, but very similar to obstruction **GFR is a good test used to check how much blood passes through the glomeruli each minute → if kidneys are working well! RENAL CALCULI (KIDNEY STONES) - Another cause for obstruction; also known as uro-lithiasis (presence of kidney stones) - Consist mostly of calcium salts (calcium oxalate or calcium phosphate) - Patients urine will have high pH (low pH prevents sediments from staying) - Usually idiopathic (if they are under 5mm they can be passed) - Pre-disposing factors o Chronic UTIs (infection, inflammation and stricture can lead to formation of stones due to narrow passage) o Urinary stasis (decrease of urine output/stoppage of urine) o High concentration of stone forming substances in urine (made from Ca+ related to parathyroid hormone) o Hypercalcemia and gout (uric acid stones) - Types of kidney stones: o Calcium stones – smallest and most commonly found in middle aged men with family history. May follow prolonged immobilization (normally due to GI reabsorption of calcium) o Struvite – formed following and infection with urea-splitting organisms; made from magnesium ammonium phosphate; women at greater risk o Uric acid stones – caused by gout; very common in people with liver failure o Crystine (amino acid) stones – occur in people with cystinuria (rare congenital disorder) o Staghorn calculi – form in renal pelvis and extend into calyces ▪ Commonly associated with infection ▪ Require surgical removal - Manifestations: silent in renal pelvis ; if the stones are in the ureters, patient’s will experience severe acute pain (renal colic), hematuria, flank pain - Diagnosis based on: medical and family history, blood tests (BUN, plasma, creatinine) and urine tests (pH, RBC, WBC) o Abdominal x-ray, IV pyelogram (x ray of the kidneys), ultrasound - Treatment o Pain medications and drinking lots of water o Dilute concentration of stone forming substances by increasing urine flow (if PTH, Vit C and D are high, there is a tumor) o Decrease dietary intake or endogenous production of stone forming substances o Lithotripsy: non invasive procedure that fragments stones, or surgery for large stones - Complications – urinary tract obstruction, hydronephrosis, hydroureter, renal abscess, renal failure BENIGN PROSTATIC HYPERPLASIA (BPH) - Increase in size of prostate gland - Present in 50% of males between 40-60, 95% of males over 70 years o Clinically significant in 10-15% of men over 60 years o The prostate produces the fluid that dilutes sperm. As you age, there is less need for the fluid, so it accumulates - Typical obstructive symptoms include: o Difficulty urinating despite straining, and always having the urge to pee ▪ Urinary retention can damage mucosa in the bladder and can lead to diverticula o A weak, interrupted stream of urine o Dribbling at the end of urination - Etiology (causes) o Idiopathic o Possible due to hormonal imbalance (low level of androgens relative to estrogens) o Enlarged gland (it is normally only 3cm) → obstruction depends on the size of the prostate o Nodules present throughout the gland o Periurethral area is commonly involves o Partial or complete obstruction to urine outflow leads to urinary retention, overflow incontinence, bladder hypertrophy NEUROGENIC BLADDER - Loss of control of bladder - The body normally does not let the bladder fill up → people with neurologic damage cannot tell the bladder when to empty o Either the sphincter is always open or always closed (either incontinent or retaining) - Not many treatment options - Patient may be immobile - Patients present with the feeling of fullness and difficulty emptying their bladder, a slow stream, having to strain, etc. - Vesicourethral Reflux (VUR) o Urine flows from the bladder to the ureters o Most common in infants and young children with UTIs or post-menopausal women o Can be congenita or anatomical URINARY INFECTIONS - An infection in any part of the urinary system (urethra, prostate, bladder, ureter, kidney) - Usually caused by bacteria (diagnosis by urine bacterial culture) o Commonly caused by colonic bacteria (E. coli) o Urinalysis can show increased leukocyte esterase and microscopy can reveal WBCs and bacteria - Infections cab be ascending (coming from urethra up), or descending (coming down from the kidney → can also be coming from lung, heart or other parts of the body) - Predisposing factors o Use of diaphragm spermicide (caused by healthcare worker) o Urologic instrumentation (caused by healthcare worker) o Catheterization (caused by healthcare worker) o Spinal cord injury (immobility and loss of hygiene) o Neurogenic bladder o Urinary tract obstruction o Immobilization Female Predisposing Factors: Male Predisposing Factors - Anatomical factors (shorter urethra → bacteria has - Obstruction and stasis of urine flow due to kidney less distance to travel to get to the bladder; urethra so stones, BPH, neurogenic bladder close to the anus) - Dysuria - Sexual intercourse (honeymoon cystitis) → forcing - Pyuria urethral microorganisms into the bladder (educate - Fever women to urinate after intercourse to flush bacteria) - Leukocytosis - Pregnancy → decreased bladder tone, increased - Malaise retention, high glucose = more microorganisms, - Flank pain respiratory alkalosis (solution is to wipe front to back and do kegel exercises) LOWER URINARY TRACT INFECTIONS Urethritis – inflammation of the urethra - Causes: STDs (chlamydia and gonorrhea), trauma (e.g., jagged kidney stones) Cystitis – inflammation of the urinary bladder - Most common UTI o Usually due to E. coli or Staph (MOST BACTERIA WILL EITHER COME FROM GI TRACT OR THE SKIN) ▪ Occasionally can be Proteus or Klebsiella - Want patients to pee a lot and have acidic urine → give them cranberry juice - Mild inflammation can cause hyperemic mucosa (bladder will be pink when it should normally be gray) o Occurs when excess blood builds up inside vascular system - More advanced – hemorrhagic cystitis (diffuse hemorrhage) or suppurative cystitis (pus formation on epithelial surface) → lots of bleeding - Prolonged – ulcerative cystitis (proteinuria, RBC and WBC) - Most severe – gangrenous cystitis (necrosis of the bladder wall) - Clinical manifestations o Frequency, urgency, dysuria, suprapubic and lower back pain (can be asymptomatic) o Hematuria, cloudy urine, flank pain - Diagnosis with urine bacterial culture - Treatment with antibiotics UPPER INTARY TRACT INFECTIONS – ACUTE PYELONEPHRITIS - Bacterial infection causing inflammation of the kidneys (renal pelvis, calyces and medulla) - Will see increased WBCs in the blood; collecting ducts will become inflamed - Usually due to E. coli, Proteus, or Pseudomonas - Microorganisms usually ascend ureters but can also enter from the blood - Affects one or both kidneys → will see fibrosis and scar tissue (interference with tubular absorption) - Predisposing factors: o Urinary obstruction o Vesicourethral reflux o Pregnancy o Diabetes o Neurogenic bladder o Catheterization o Sexual activity (females) o Also some factors related to UTI because the infectious process is the same - Pathology o Renal inflammation and edema o Infiltration of WBCs to medulla o Purulent urine (sign of bacterial infection) o Can lead to abscess and necrosis or papillae o LOOK AT WBC CAST TO DIFFERENTIATE → WBC cast indicate inflammation of the kidney - Clinical Manifestations o Chills/headache o High fever o Flank pain (if you lightly thump the flank the person will have extreme pain) o WBC and bacteria in urine o Painful urination - Diagnosed via urine culture - Treatment – antibiotics for 2-3 weeks o 500mg ciprofloxacin BID for 7 days o 750mg levofloxacin OD for 5 days CHRONIC PYELONEPHRITIS - Recurrent pyelonephritis that can occur in people unable to care for themselves - inflammation, scarring of kidneys d/t persistent, recurrent autoimmune response to infection - risk factors: kidney stones, reflux (repeated renal infections) - Etiology: chronic obstruction → progressive inflammation, fibrosis in interstitial spaces between tubules → tubule destruction → impaired urine-concentrating ability, renal failure - chronic interstitial nephritis lesions of chronic pyelonephritis also caused by: analgesic drug toxicity ischemia irradiation immune complex diseases vesicoureteral reflux (VUR). - Contrast Induced Nephropathy (CIN) – kidney problems are caused by the use of contrast dyes (risk increases for people with diabetes, heart and blood diseases and CKD) - Treatment to relieve underlying cause (obstruction, infection) - Minimal early symptoms (such as hypertension, dysuria, flank pain) but progresses to renal failure o Proteinuria, WBC and epithelial cells in the urine, issues related to electrolytes (high chloride will lead to acidosis) GLOMERULAR DISORDERS - Caused by infections, toxins, immune response - Inflammation of the glomerulus will lead to changes in the structure of the capillary walls → will cause proteinuria and altered GFR - Urinary sediment - Issues with triglyceride clearance (if they are not cleared they will lodge in the blood vessel and lead to kidney failure) - Damage to the glomeruli and letting protein/RBC leak into urine o Buildup of waste products o Albumin leaking into the urine can cause the blood to lose its capacity to absorb extra fluid from the body - Clinical hallmarks: edema, proteinuria, hematuria, increased BUN and creatinine, decreased protein in the blood GLOMERULONEPHRITIS - RBC CAST, hematuria, proteinuria, neutrophils → RBC casts will not be visible without microscope, but you will see hematuria - Can be classified by cause, pathological lesions, disease progression or clinical presentation - All types are characterized by disturbance of epithelial or podocyte layer of glomerular membrane ACUTE GLOMERULONEPHIRITIS - Inflammation of glomeruli - Usually associated with Strep infection ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS (APSGN) - Abrupt onset 7-10 days after strep throat or skin infection (occasionally follows bacterial endocarditis) → by the time we find out, the infection has already passed - Pathogenesis: o Positively charged strep antigen deposits in negatively charged glomerular basement membrane ▪ After infection, antibodies are formed against strep antigens and the antigens get stuck on the basement membrane o Attracts neutrophils, macrophages (causes further harm) o Inflammatory mediators damage cells lying on the basement membrane - Clinical manifestations appear 10-21 days post infection o Hematuria, RBC cast, proteinuria o Low GFR, oliguria (low urine output) o Hypertensions o Edema around eyes, feet, ankles (fluid not coming back to blood vessel due to losing proteins) o Ascites, pleural effusion in some cases - Diagnosis on basis of clinical manifestations plus history of strep infection (commonly found on the skin) - Renal biopsy – immune complexes deposited in glomerulus and capillary endothelial cells (thickened filtration membrane and low GFR) - Treatment o Medication to lower BP, angiotensin converting enzyme inhibitor, angiotensin receptor blockers o Anti inflammatory o Dialysis and transplant to treat irreversible failure o Managing fluid overload - Prognosis o Usually resolves in children and most adults with no significant loss of renal function or recurrence of disease o Can progress to chronic glomerulonephritis and renal failure o Disease regresses over several weeks CHRONIC GLOMERULONEPHRITIS - Prolonged progressive renal disorder - Not S+S until 80% of kidney function has been lost (disease skips the acute stage) - Pathophysiology Pathophysiology - antigen-antibody complexes embed within thickened glomerular capillary filtration membrane circulating complexes anti-GBM (Glomerulus's basement membrane) Ab’s - severity of damage and renal insufficiency is related to size, number, location, duration of exposure, type of antigen- antibody complexes - inflammatory reaction → glomerular cell damage, proliferation of extracellular matrix → altered filtration membrane permeability → protein, RBCs lost to urine Clinical manifestations: - hematuria (smoky-brown urine) with RBC casts - proteinuria - renal insufficiency, after 10-20 yrs → nephrotic syndrome, end-stage renal failure - Nephrotic syndrome is a kidney disorder that causes your body to pass too much protein in your urine. Nephrotic syndrome is usually caused by damage to the clusters of small blood vessels in your kidneys that filter waste and excess water from your blood. - diagnosis confirmed by progressive development of clinical symptoms, urinalysis (proteinuria, RBCs, WBCs, casts), renal biopsy - treatment: antibiotics for underlying infections; corticosteroids to bring down antibody synthesis, inflammation o slow down the immune system o treat other health issues (vaccinations, high BP, high cholesterol, etc.) o use of diuretics (related to proteinuria) NEPHOTIC SYNDROME - massive proteinuria leading to edema - can be caused by a variety of disorders (diabetes, lupus, etc.) → most common cause in children in minimal change disease o foot processes of podocytes that cover the basement membrane are damaged - edema decreases the amount of intravascular fluid and decreases BP → kidneys will release renin o adrenal glands then release aldosterone to retain Na and H2O → more fluid to contribute to edema - lab findings include hypoalbuminemia, hyperlipidemia, proteinuria (over 3.5g/day) - need steroids, biopsy and immunosuppressants NEPHRITIC SYNDROME - inflammation of the glomeruli and renal dysfunction - caused by IgA nephropathy (Berger’s disease), postinfectious glomerulonephritis - can present with oliguria, hypertension, hematuria (brown) - lab findings indicate hematuria, proteinuria (less than 3g/day), elevated BUN and creatinine and RBC casts RENAL TUMORS BENIGN RENAL TUMORS - Benign tumors (adenomas) are uncommon - They are encapsulated and usually located near the renal cortex - Removed surgically due to potential for malignancy MALIGNANT RENAL TUMORS - Genetic condition - Renal carcinomas o 85% are adenocarcinomas (clear cell carcinoma and granular cell carcinoma) o 10% are transitional cell carcinoma - Renal cell carcinoma o Risk factors: smoking, age, males o Flank pain, hematuria and palpable flank mass (but patient will not have all three) o First line of treatment is surgical eradication - Better prognosis if within renal capsule o Likely comes from tubules because it has epithelial origin o Related to obesity, hypertension, heavy use of chemicals - Transitional cell carcinoma (renal pelvis) o Usually grow unilaterally o Invade the liver, colon or pancreas o Metastasis through lymph and blood to the lungs, adrenal glands, liver and bone o Location determines whether it will become malignant o Manifestations ▪ Early stage is silent (hematuria is normally the first sign) ▪ Hematuria, flank pain, palpable mass, weight loss in late stage BLADDER TUMORS most caused by smoking and chlorine in the water workers exposed to arylamines used in the manufacture of aluminum, rubber goods, aniline dyes used in leather goods, or in pest control, textile manufacturing, printing and hair dressing Types: transitional cell carcinoma adenocarcinoma squamous cell carcinomas **angiogenesis increases risk of hematuria Manifestations: may be asymptomatic or manifest as hematuria, frequency, pelvic pain, infection Metastases: metastases to lymph nodes, liver, bones, lungs Treatment: surgery: tumour excision, cystectomy chemotherapy (if already spreading) radiation Cystectomy is a complex surgical procedure in which a surgeon removes some or all of the urinary bladder. The bladder stores urine before you pass it from your body. Most often, doctors perform bladder removal surgery to treat invasive bladder cancer. Doctors sometimes perform cystectomy for benign disorders affecting the bladder and urinary system. RENAL FAILURE - Kidney failure is when your kidneys have stopped working well enough for you to survive without dialysis or a kidney transplant. Your kidneys have lost their ability to filter waste from your blood. Also includes failure to produce hormones Stages of Renal Failure ◼ based on % of kidney function remaining ◼ kidneys have tremendous reserve potential ◼ must lose 75% of function before significant manifestations appear ◼ classification: ❑ renal insufficiency: 25% ❑ renal failure: 10-25% ❑ end stage renal failure: < 10% 2 blood test we look at to determine the kidney function: ◼ Azotemia: - Increase in serum urea, blood nitrogen level - May be accompanied by increase in creatinine, decreased urine output, hypotension, vomiting - Associated with renal insufficiency, renal failure - Hypovolemia, increased thirst, decreased urine output, vomiting - Azotemia is a condition that occurs when your kidneys have been damaged by disease or an injury. You get it when your kidneys are no longer able to get rid of enough nitrogen waste. Azotemia is usually diagnosed by using urine and blood tests. These tests will check your blood urea nitrogen (BUN) and creatinine levels. Abnormally high levels of nitrogen in the blood (NITROGEN WITHOUT SYMPTOMS) - **Azotemia and Uremia difference: Uremia condition of Azotemia with symptoms. When its asymptomatic: it is azotemia. ◼ Uremia: syndrome of renal failure (NITROGEN WITH SYMPTOMS) ◼ Anorexia, N&V due to uremic wastes in the GI tract (abdomen distention, more basic environment in stomach, infections, constipation, diarrhea, stomach bleeding due to ulcers) ◼ Neurological changes: due to metabolic acidosis (confusion) ◼ Fluid and electrolyte imbalance (fluid retention, edema) ◼ Bleeding, anaemia due to decreased erythropoietin secretion, pruiritis ◼ Patients will feel extremely itchy (waste “under the skin”) ACUTE RENAL FAILURE Acute kidney injury (AKI), also known as acute renal failure (ARF), is a sudden episode of kidney failure or kidney damage that happens within a few hours or a few days. AKI causes a build-up of waste products in your blood and makes it hard for your kidneys to keep the right balance of fluid in your body. Acute renal failure has an abrupt onset and is potentially reversible. There are three potential causes: prerenal, intrarenal and postrenal Prerenal Failure ◼ d/t impaired renal blood flow ❑ result of renal vasoconstriction ❑ hypotension ❑ hypovolemia (shock, burn, dehydration) ◼ hemorrhage (heart attack, cardiogenic shock) ❑ inadequate cardiac output ❑ 60% cause acute renal failure ◼ causes  GFR → embolism or clot Intrarenal Failure ◼ Commonly caused by acute tubular necrosis due to ischemia or nephrotoxic agents ◼ ischemic type due to: ❑ prerenal causes ◼ major trauma, surgery → haemorrhage ◼ severe burns, sepsis → hypovolemia ◼ muscle trauma → myoglobinemia ◼ blood transfusion reactions (immune system attacks transfused blood cells ◼ nephrotoxic type - caused by harmful chemicals: ◼ heavy metals (lead, mercury) ◼ organic solvents ◼ ethylene glycol – used to make antifreeze ◼ pesticides ◼ Chemotherapies ◼ aminoglycoside antibiotics: amikacin, tobramycin, gentamicin ◼ radio contrast media ❑ necrosis usually limited to proximal tubules Postrenal Failure (5-10%) ◼ usually due to urinary tract obstruction that affects both kidneys ◼ causes: bladder outlet obstruction, BPH, diagnostic catheterization of ureters ** If ARF cannot be managed conservatively, {Uremia with hyperkalemia ( > 6.5 mEq/L), severe metabolic acidosis, pulmonary edema, etc. }, dialysis may be required Consequences ◼ severe cases may → : ❑ hypertension (increase already high HPT, people with DB) ❑ peripheral, pulmonary edema ❑ acidosis ❑ hyperkalemia → cardiac arrhythmias (dialysis, give chemicals to get rid of potassium, Humulin R, buy us time) ❑ End Stage Renal Disease (ESRD) End-Stage Renal Disease (ESRD) is a medical condition in which a person's kidneys cease functioning on a permanent basis leading to the need for a regular course of long-term dialysis or a kidney transplant to maintain life. Stages of ARF Stages of ARF Stage Timeline Characteristics Stage Timeline Characteristics 1. Initiating From injury -Renal flow at 25% of normal 3. Diuretic 1-3 weeks -Gradual or abrupt return of glomerular onset to cell -Oxygenation to tissue at 25% filtration; kidney is able to excrete waste but death; hours -Urine output ≤30ml/hr not conserve water to days -Urine Na+ excretion > 40 mEq/L -↑ urine ouput (1-4L/day) -25% death from ARF occurs during this phase 2. Oliguric- Usually -Kidney has lost most /all of its anuric begins regulatory/excretory functions 4. Recovery Several -Begins when the BUN is stable and lasts until within a day -Acute uremic symptoms may months to patient returns to normal activity of injury appear (from waste build-up) a year -Edema decreases; fluid & electrolyte balance and lasts 1-3 -Urine output < 400mL/24 hours is restored -Renal function may never return to baseline; weeks -Dialysis may be required GFR is usually 70-80% of normal CHRONIC RENAL FAILURE - Chronic irreversible decline in renal parenchyma with loss of function - Occurs over years - Asymptomatic until late in its course - Excretion of water, electrolytes, nitrogenous wastes due to loss of nephrons Causes: - Diabetes/diabetic neuropathy (40%) - Hypertension (25%) - Chronic glomerulonephritis (11%) - Chronic ischemia - Hereditary, congenital, cystic disease Stage 1 – decreased renal reserve - 40-50% function remaining - Asymptomatic - BUN and creatinine are high normal - Normal functioning is evident as long as client is not exposed to unusual physiologic or psychological stress Stage 2 – renal insufficiency - 20-40% function remaining - Symptomatic - BUN and creatinine are above normal → azotemia - Impaired urine concentration, nocturia, mild anemia - Need medication and diet control - Renal function impaired by stress - Decrease in GFR to 60-90mls/min Stage 3 – uremia (ESRF) Less than 10% function remaining Symptomatic Severe azotemia (high nitrogen in the blood) Acidosis, impaired urine dilution, severe anemia Electrolyte imbalances (hypernatremia, hyperkalemia, hyperphosphatemia) Clinical Manifestations - Urinary system Oliguria, anuria Low creatinine clearance Retention of sodium, water, potassium in later stages Patients die in their sleep - CNS Fatigue, drowsiness, inability to concentrate Coma, seizures, memory loss - Skin Pale yellow brown colour (due to RBC and erythropoietin not being produced) Uremic frost, pruritic, odor of urine - GI System Anorexia, N/v, peptic ulcers, constipation, diarrhea - Resp System Pulmonary edema Odor or urine on breath (urine breakdown by salivary gland) Develops acidosis - CVS Hypertension, pericarditis (third spacing), anemia Bleeding tendencies, alterations in body fluids (electrolytes, pH) Elevated BUN and creatinine - MSK Renal osteodystrophy, muscle twitching and cramps Stress fractures, muscle weakness High phosphate and low calcium Treatment - Manage protein intake, supplemental vit D, maintain sodium and fluid, restrict potassium, adequate caloric intake, management of dyslipidemias - Erythropoietin as needed, ACE inhibitors or receptor blockers (control systemic hypertension and provide renoprotection), dialysis and renal transplantation  Stages of Chronic Kidney Disease Stage Severity GFR ml/min Symptoms 1 Kidney damage: ≥ 90 Usually none normal or ­ GFR HTN common 2 Kidney damage: 60-89 Subtle (850 mls / day) mild ↓ GFR HTN 3 Moderate: ↓ GFR 30-59 Mild (500 mls / day) HTN 4 Severe: ↓ GFR 15-29 Moderate (260 mls / day) HTN Hyper-phosphatemia Anemia 5 End-stage kidney 60 yrs may be squamous cell carcinoma, melanoma, sarcoma, adenocarcinoma more often metastatic than primary lesion S&S: vaginal bleeding, urinary symptoms, discharge, remove it, and chemo if it spreads Cervical Cancer Cervical Cancer HPV is the culprit, also smoking, STI, poor nutrition etc. 3rd most prevalent gynecological cancer 1 in 8 women have dysplasia by age 20 progressive disease classified according to histology from cervical interesting condition a-epithelial neoplasia (CIN) to invasive carcinoma the premalignant lesion precedes invasive carcinoma by years early changes asymptomatic, detected by Pap smear n  19 Manifestations: - abnormal menses - post menopausal bleeding, bleeding after intercourse - bleeding may lead to anemia - serosanguinous or yellowish vaginal discharge, foul odour. Treatment: - (Cryosurgery, laser surgery, radiation) depends on degree of neoplastic change; size, location of lesion; extent of metastases Mild Dysplasia (CIN I) Normal Moderate Dysplasia (CIN II) Severe Dysplasia (CIN III), CIS Invasive Carcinoma n  20 Endometrial Cancer most prevalent gynecological malignancy usually occur to women after menopause cause: diabetes, HPT, obesity, taking estrogen without using progesterone, uterine polyps, history ovarian cancer vaginal tissue and endometrial layer constantly regenerate screening for early detection important postmenopausal bleeding Diagnostic tool: PAP, CT, MRI, ultrasound, scraping of uterine wall S&S: bleeding, spotting, especially after intercourse, enlarged uterus, pain in the abdomen cytologic sampling - biopsy, Dilation & Curettage treatment depends on extent of disease - surgery: ◼ salpingo-oophorectomy ◼ radical hysterectomy (abdominal, vaginal) ◼ pelvic lymph node dissection - radiation ◼ external beam pelvic radiation ◼ intracavitary irradiation - chemotherapy A salpingo-oophorectomy is the removal of one (unilateral) or both (bilateral) of your ovaries and fallopian tubes. Curette: Scrape some of the uterine tissue for I biopsy. Dilation and curettage refers to the dilation of the cervix and surgical removal of part of the lining of the uterus and/or contents of the n uterus by scraping and scooping  21 Ovarian Cancer risk factors: - family history of ovarian, breast (BRCA1 gene), uterine, pancreatic, colon cancer, history of breast cancer (10% cause) - postmenopausal - 90% of time sporadic cause. - infertility, prolonged unsuccessful use of fertility drug - early menarche, late menopause, nulliparity, 1st child after age 30 - high-fat diet - if the incident of cancer can be decreased by hormone, this is the type of idea which give rights to hormonal therapy pregnancy, childbirth, use of Oral Contraceptive decrease risk Manifestation: - asymptomatic majority of the time; silent disease. Very general sign of symptoms (abdominal pain, swelling) - usually advanced at time of diagnosis - Dx on basis of transvaginal ultrasound, CT scan, MRI, to localize tumor - tumor marker CA-125 may also be assessed Treatment depends on how far the disease has progressed, if it has spread quite a bit: chemo, if it hasn’t spread, only one lesion we do radiation, mortality unchanged for last 20 years, 5 year survival rate is 46%, not very high Survival rate much higher if detected at stage 1 or II n  22 Benign Disorders of the Breast Galactorrhea Galactorrhea is a milky nipple discharge unrelated to the normal milk production of breast-feeding. Galactorrhea itself isn't a disease, but it could be a sign of an underlying problem. It usually occurs in women, even those who have never had children or after menopause. But galactorrhea can happen in men and even in infants. secretion of milky substance from breast of woman who is not pregnant or nursing manifestation of a hormonal imbalance (prolactin level high, TSH level very high, sth to do with pituitary) treatment; hormonal therapy, surgical removal if its adenoma related. n  23 Fibrocystic Change (FCC) physiologic nodularity present in ~50% of menstruating women, some changes present in up to 80% of all women includes microcysts, macrocysts, adenosis, apocrine change, fibrosis, fibroadenomas, epithelial proliferation manifestation: increase menstrual pain, 3 types of changes: - Cystic - Fibrous - Epithelial proliferative Manifestation: tenderness of breast, pain fluctuate depends on the size of lesion, progressively worse till menopause. Fibrocystic change (FCC) is a general term used to describe a group of non-cancerous changes that often develop together in the breast. It is a common finding seen in up to 60% of reproductive-aged women. FCC is believed to develop in response to stimulation from hormones such as estrogen and progesterone. FCC involves the ducts, glands, and stroma normally found in the breast. n  24 Breast Tumors m Outline smooth, solid mobile circumcised mass. Much easier to remove Treatment: surgery to remove, chemo very common, Late stage: cyst drainage to decrease the pain n  25 risk factors: reproductive hormonal environmental Familial gender age personal history of cancer sedentary lifestyle Reproductive risk factors: - woman's age when 1st child is born (risk  for younger mothers) - nulliparous women have  risk - late menarche, early menopause  risk Hormonal risk factors: - combined estrogen progesterone Oral contraceptives increase risk, - long term (>10 years) hormonal replacement therapy Environmental Risk factors - alcohol - high fat diet, obesity in women > 50 - high dose ionizing radiation used to treat other conditions (especially during adolescence) Familial Risk factors - most women have no family history - risk  in women with mother or sister with breast cancer -  with # of relatives with breast or ovarian cancer - hereditary breast cancers n  26 Pathology - adenocarcinoma - don’t grow large but metastasize early to bones, lymph nods and lungs - majority of carcinomas occur in upper outer quadrant (contains most glandular tissue) Manifestations first sign usually painless lump with no classic characteristics may be palpable nodes in axilla, dimpling, nipple retraction ulceration, hemorrhage bone pain from metastasis evaluation by: mammography percutaneous needle aspiration biopsy (defining test) hormone receptor assay Estrogen receptor/progesterone receptor (ER/PR) tests are used to help guide breast cancer treatment. Receptors are proteins that attach to certain substances. ER/PR tests look for receptors that attach to the hormone’s estrogen and progesterone in a sample of breast cancer tissue. Treatment: - Surgery - Radiation - Chemotherapy - Hormone therapy based on extent of cancer n  27 Disorders of the Male Reproductive - System n  28 Disorders of the Penis Phimosis foreskin too tight any age poor hygiene, chronic infection among or kids before age of 3, subside over time, however there are times phimosis will last such as poor hygiene, chronic infection of penis glands, Diabetes also increase risk S&S: inflammation, edema, erythema, tenderness, purulent discharge, infection etc. Para-Phimosis retracted foreskin too tight to be returned to cover glans may require surgery to prevent necrosis of glans this continues to happen once or twice, may have to ask pt to go through circumcision from recurring. n  Composition of the Penis 29 corpus cavernosum (unengorged) corpus Involved in erection cavernosum (unengorged) corpus cavernosum (engorged) Colles’ fascia corpus cavernosum (engorged) tunica albuginea urethra corpus spongiosum Protect Urethra from compression during erection The tunica albuginea forms a thick fibrous coat to the spongy tissue of the corpora cavernosa and corpus spongiosum. It consists of two layers, the outer longitudinal and the inner circular. n  30 Peyronie’s Disease (Bent nail syndrome) tough, fibrous thickening of tunica albuginea around the corpus cavernosum - local inflammatory reaction lateral curvature of penis during erection related to DM, dupuytren contracture, use of beta blockers - Dupuytren's contracture is a hand disorder in which the fingers bend towards the palm and cannot be straightened. The little or ring fingers are most commonly affected, but any or all fingers can be involved. usually affects middle aged men, which leads to: - painful erection - painful intercourse may → impotence no definitive treatment - Medication therapy: Colchicine, mostly known for its treatment for gout, but can also be used for this. - Surgery, graph below. Spontaneous remission Peyronie's disease is a disorder in which scar link tissue, called plaque, forms under the skin of the penis—the male organ used for urination and sex. The plaque builds up inside the penis, in the thick elastic membrane called the tunica albuginea. The tunica albuginea helps keep the penis stiff during an erection. n  31 Priapism prolonged, painful erection not associated with sexual arousal children: – leukemia, sickle-cell disease adults – 60% cases idiopathic – 40% associated with sickle-cell disease, s.c. trauma, leukemia, pelvic tumours – *if you notice a man after car accident get erection, DO NOT move them, might indicate mid to low back spinal cord injury. Sympathetic nervous system damaged. urologic emergency (rapid treatment necessary) - Hydrate (if its sickle cell related and give pain med), - Vasoconstrictors (go to - Aspirate blood (inject needle in corpus cavemosum, pull blood back 60cc syringe, to evacuate blood) Complications: infection fistulas strictures necrosis Balanitis inflammation of glans penis associated with poor hygiene, phimosis accumulation of smegma under foreskin → irritation, infection treatment: keep the area clean, meds and topical creams, if repetitive leads to circumcision n  32 Penile Cancer cause unknown – ? smegma accumulation – Smegma is the thick, white, cheesy substance that collects under the foreskin of the penis. It's more common in uncircumcised men who don't clean that area well enough. 95% squamous cell carcinomas Risk factors: HPV precancerous lesions, squamous cell cancers treatment for carcinoma in situ – topical cream [5-fluorouracil (5-FU)] – local excision – Moh’s surgery (we have pathologist present and is therefore able to translate abnormal findings on the tissue map into appropriate sequential tumor removal, since we want to save as much good tissue as possible) in more advanced stages: – surgery (including laser surgery, cryosurgery, chemosurgery) – lymphadenectomy – radiation or chemotherapy penile cancer small, flat ulcerative lesion on glans or foreskin ® entire penile shaft n  33 Disorders of the Scrotum The scrotum is a part of a male's body that is located below the penis. The scrotum is the sac (pouch) that contains the testes, epididymis, and the lower part of the spermatic cord (blood vessels and vas deferens). Varicocele Varico-Cele: vein blockage – abnormal dilation of vein within spermatic cord – varicose vein in the scrotum – cause swelling, infertility if we don’t correct – blood become hypoxic, can happen on both side. – due to incompetent valves in spermatic vv. –  testicular blood flow, interferes with spermatogenesis → infertility – Treatment: surgical procedure, or compression device go around scrotum, promote blood to go back into the cardiovascular circulation n  34 Hydrocele Hydro-Cele: fluid blockage – collection of fluid within the processus vaginalis is an embryonic developmental outpouching of the parietal peritoneum. It is present from around the 12th week of gestation and commences as a peritoneal outpouching. Hydrocele is common in newborns and usually disappears without treatment by age 1. – most common cause of scrotal swelling – congenital hydrocele in infants may resolve spontaneously – treatment: drain fluid, does not cause serious health issue, but scrotum enlarged. Spermatocele Sperma-Cele: sperm blockage – retention cyst – located between head of epididymis & testicle – vary in size – milky fluid containing sperm – usually asymptomatic – A spermatocele is an abnormal sac (cyst) that develops in the epididymis — the small, coiled tube located on the upper testicle that collects and transports sperm. Noncancerous and generally painless, a spermatocele usually is filled with milky or clear fluid that might contain sperm. – Scrotal haematoceles are collections of blood within the scrotal sac, but outside of the testis, if it’s enlarged, might have to evacuate like hydrocele. n  35 Disorders of the Testis testis, plural testes, also called testicle, in animals, the organ that produces sperm, which is the male reproductive cell, and androgen, which is the male hormones. In humans the testes occur as a pair of oval-shaped organs. They are contained within the scrotal sac, which is located directly behind the penis and in front of the anus n  36 Cryptorchidism undescended testis or testes. testes remain in abdomen or descend to puboscrotal junction most common congenital condition involving testes occurs in 3% of full-term, 20% of premature males most descend within 1 yr. uncorrected, → impaired fertility but does not prevent puberty or secondary sex characteristics (testes have to be in the scrotum, because it has lower temperature for sperm to be produced)  risk of testicular cancer Torsion of Testis testis rotates, twists aa. and vv. → ischemia, necrosis surgical emergency usually happen to new-borns 1-3 Testicular torsion occurs when a testicle rotates, twisting the spermatic cord that brings blood to the scrotum. The reduced blood flow causes sudden and often severe pain and swelling. Extremely extremely painful, sudden onset, require immediate treatment. n  37 Orchitis acute inflammation of testis extension of systemic infection (possible trauma) treatment is supportive abscess usually → orchiectomy Testicular Cancer 95% (most curable cancer) but needs to be diagnosed early enough most are germ cell tumours – seminomas (pure classical germ cell of testes) , non-se