533-Exam-1-Comp-Notes

○ Labs ■ UA, CBC, Uric Acid ■ CMP (K, Ca, BUN/Creatinine) ● Know what the panel represents where you’re at! ■ Glucose, Lipid panel ■ ECG to eval for Left ventricular hypertrophy (LVH) or ischemic Heart dz ○ Management is based on: ■ Patient’s age, ethnicity, comorbidities & BP guidelines ■ Individualized ■ Utilized shared decision making ■ If meds started F/U in 1-4 weeks to assess BP ● Chemistry profile 5-7 days after the med is started ● If pt has renal dysfunction GFR < 30 or HF start on loop diuretics & follow ● MOnitor Q3 months to determine tx efficacy & monitor electrolytes & renal status ○ Vascular effects of sustained HTN ■ Bruits in carotid, aorta & renal arteries ■ Cardiac ● Gallops, displaced apical impulse, Left ventricular enlargement which indicates complications of HTN & affects tx decision ■ Cerebral ● Deficits on neuro testing ■ Retinal ● Arteriolar narrowing, AV nicking, exudates, hemorrhages & papilledema ■ Renal ● Renal artery bruits or enlarged kidneys ● Oliguria, hematuria, proteinuria & RBC casts ■ Peripheral ● Diminished pulses, thin skin, loss of hair ● STriae, neurofibroma & pruritic areas JNC 8 Guidelines from 2014 *NOT using these guidelines anymore* do NOT need to know the algorithm! ● All adults > 18 yo w/ HTN ○ Implement lifestyle modifications ○ Set BP goal, initiate BP lowering med based on algorithm ● Lifestyle changes: based on pts age, ethnicity, comorbidities & BP guidelines ○ Smoking Cessation ○ Stress management ○ Control Blood sugar & lipids ○ Diet ■ Healthy diet ex DASH ■ Mod alcohol consumption (1 drink a wk for gals, 2/wk for boys) ■ Reduce sodium intake to no more than 2300mg/day ○ Physical activity ■ Mod to vigorous activity 3-4 days a week approx 40 min a day. 150 min/wk ■ Wt loss ● Drugs of Choice ○ ACE Inhibitor (ACEI) ■ Renal protective ● Lookin at you DM and CKD pts ■ Monitor K & renal function ○ Angiotensin receptor blocker (ARB) ■ Renal protective ● Also Dm & CKD pts ■ Monitor K & renal function ■ Better for Asian patients ○ Thiazide diuretic ■ AA pts ■ Increase Uric acid levels ● Do not give to gout patients ○ Calcium Channel Blocker (CCB) ■ Per JNC 8 works better on Asian & AA

■ Atherosclerosis ● More risk of cholesterol deposits w/in the walls of the blood vessels leading to hardening ● Can result in HTN, CAD, HF ● Increased risk for stroke, renal disease ○ Hormonal changes ■ Insulin resistance ■ Lead to DM2, metabolic syndrome ■ Infertility ○ Pulmonary changes ■ Sleep apnea ● Increases cardiovascular risk ■ Increased risk of asthma ■ Exercise intolerance ○ Increased risk of cancer ■ Breast, colon, renal, endometrial, esophageal, stomach, pancreas, liver, ovarian cancer ● Differential Dx ○ PCOS ■ Acne, male pattern baldness, hirsutism ■ Linea nigrans ○ Hypothyroidism ■ Absent eyebrows, karetinemia on hands ○ Cushing Syndrome ■ Upper back fat pad, moon face, thin skin, easily bruising ■ Screen! ● 24 hour free cortisol level, dex suppression test etc ○ Sleep Apnea ■ Men w/ neck circumference of ■ Women w/ neck circumference of ○ Heart failure ○ Drug induced Obesity ■ Prader-Willi Syndrome ■ Bardet-Biedl Syndrome ■ Alstrom ○ Secondary Neurological Obesity ● Interprofessional Collaborative management ○ Motivational interviewing - The 5 As ■ Ask ● Ask if it’s okay to discuss weight ■ Assess ● BMI ■ Advise ● Health Risks ■ Agree ● Agree w/ pt on realistic Goals ■ Assist ● Assist pt in finding resources ○ Lifestyle Interventions ■ Energy deficit ● Reduce calories ■ Physical activity ■ Behavioral changes ○ Eating for Wt Loss ○ Pharm Wt Loss ■ CNS stimulation, insomnia, nervousness, tremors, dry mouth ○ Surgery ■ Bariatric surgery does not cure obesity! ■ These pts have nutrient deficits ex. B12, Vit A ○ SE of Wt Loss ■ Usually due to meds from chronic conditions ● Hypoglycemia, hypotension

○ Measure fasting lipids @ least annually ○ Q 2 yrs for adults w/ low risk lipid values: LDL < 100, HDL > 50, TG < 150 ACC/AHA Guidelines 2018 ● Goal: Decrease risk for ASCVD!!! ○ The goal is not to just lower the number! Think more of percentages to decrease risk ● Statin therapy recommended for: ○ Pts w/ ASCVD → High intensity statin or max tolerated dose of statin ○ Pts w/ severe primary LDL (>190) regardless of 10 yr ASCVD score → High dose statin ○ Pts 40-75 yo w/ DM & LDL > 70 → mod intensity statin ■ Do not need to calculate 10 yr ASCVD score ○ Pts 40-75 yo w/ estimated ASCVD score > 7.5% ● Drugs for HLD ○ HMG-CoA Reductase Inhibitors - Rosuvastatin (Crestor) *1st line!* ■ Crestor - less muscle ache side effects ■ Lower LDL 21-55% Lower TG, Increase HDL ■ Can cause liver inflammation ● Take a baseline LFT before starting if indicated ex. Someone w/ liver dz or at risk for liver dz ■ Myopathy to rhabdo is a risk ● Higher risk for Simvastatin ■ If pt comes in with muscle aches → D/C statin, check CK levels & renal function ● Monitor CK levels till they come down ■ Increases risk for DM ○ Bile Acid Sequestrants - Cholestyramine ■ Mod LDL decrease ■ Safe for liver patients ○ Nicotinic Acid - Niacin ■ Lower triglycerides, increase HDL ■ Causes facial flushing, GI upset ○ Fibrates - Fenofibrate (Tricor) ■ Lower triglycerides ■ If TG > 400 → check for pancreatitis ■ Increase HDL, Mod decrease of LDL ■ Monitor renal & liver function ○ Cholesterol absorption inhibitors - Ezetimibe (Zetia) ■ Good for people who cannot tolerate statin or in combo to further lower LDL in those with CVD ○ Liposoluble antioxidants - Omega 3 fatty acids ■ Mixed results ■ Monitor liver function, TG ○ PCSK9 - Alirocumab ■ Subq admin drug in specific pop ● Those w/ ASCVD on max statin w/ LDL > 100 ● OR if a pt on max statin w/ LDL > 130 ○ After initiation of lipid lowering meds get a second panel 4-12 weeks to ensure adherence & efficacy ■ Blood testing 3-12 months based on patient response ■ LFTs before starting statins! ■ CK not necessary unless the pt has muscle symptoms ○ Before starting pt on drugs ■ Make sure those w/ thyroid issues are in a euthryoid state ■ R/O secondary causes of HLD and Hyper TG before starting statins Metabolic Syndrome ● Factors ○ Central obesity ■ Waist circumference > 40 in male, > 35 female ○ Pancreas ■ Destruction of beta cells, alpha cells also affected → insulin resistance ○ HLD ■ Plaque in blood ○ Vascular changes

○ May see lethargy, hypotonia, hoarse cry, feeding problems, constipation, macroglossia, open posterior fontanelle, umbilical hernia, dry skin, hypothermia & prolonged jaundice ○ Goiter is uncommon (occurs only in infants w/ genetic defects in thyroid hormone synthesis) ○ Most cases are due to thyroid dysgenesis which includes agenesis, hypoplasia & ectopy. 10-15% of cases of congenital hypothyroidism is due to dyshormonogenesis ■ These inborn errors of thyroxine synthesis are inherited in autosomal recessive patterns & include defects in thyroid peroxidase activity, abnormalities in iodide transport, production of abnormal thyroglobulin molecules & iodotyrosine deiodinase deficiency ● Exam ○ Thyroid may look and feel completely normal ○ Pts w/ goiter w/ autoimmune thyroiditis→ Hashimoto’s Thyroiditis ○ Goiters more common in younger patients ■ Less common as pts get older ■ In elderly- may be normal ● Primary v Secondary ○ Primary ■ Most common cause is autoimmune thyroiditis in the US ● Hashimoto's → autoimmune thyroiditis coexists w/ goiter ○ Secondary ■ Pituitary dz or tumor, less common ■ Symptoms that make you think 2ndary: ● Women w/ irregular menses, HA, galactorrhea ● Normal TSH and LOW T4 = secondary hypothyroidism ○ THink there’s problems with yo pituitary! ● RF ○ Female, older age ○ Iodine deficiency ○ Irradiation for head and neck cancers ○ Meds, personal or family hx of autoimmune dz ■ Amiodarone (contains iodine) ● Effect can be seen even 2-3 years after stopping med ■ DMT1 is a risk factor ○ Down syndrome, Turner syndrome ○ Postpartum thyroiditis ○ Goiter w/ positive thyroid antibodies ○ Thyroidectomy ● Diagnostics ○ Thyroid stimulating hormone (TSH) ■ Detects either overactivity or underactivity of thyroid ■ Order w/ Reflex ● Means if the TSH is abnormal, the lab will automatically perform a free T4 ■ In pts w/ hypothyroidism → HIGH TSH ■ If normal TSH, consider pituitary conditions as they can present similarly ○ Free T4 ■ If TSH is high but T4 normal = dx of subclinical hypothyroidism ○ Thyroid peroxidase antibodies (TPO) ■ Positive in pts who have chronic autoimmune thyroiditis ■ Check in pt who has a goiter ○ Antithyroglobulin antibodies ■ Nonspecific ○ Patient sick when the test is performed? REPEAT once feeling better ○ No imaging required unless abnormality on thyroid exam ■ Ex. feel a nodule or asymmetry ● Management ○ TSH btw 5-10 + pt is symptomatic → start Levothyroxine tx ■ Dose is based on labs, age, wt ● Initial 50 mcg/day ● Younger than 30 or 40 w/ no medical hx? Start 100 mcg/day ■ Average dose: 1.6mg/kg/day ■ Low dose in pts w/ CAD or older age

● Menstrual irregularity ● Children: ○ May present w/ behavioral disturbances, decreased attention span, difficulty concentrating, emotional lability & hyperactivity ■ Severe cases → symptoms of HF ○ Exam Findings ■ Lobe of the thyroid→ listen for a thyroid bruit ○ Increased vascularity secondary to Graves’ dz ● Goiter ○ Common in pts < 60 yo ○ Soft texture, well-delineated border ○ May cause a globus sensation ■ Pretibial myxedema ● Plaques on the lower extremities ○ Orange peel appearance ■ Cardiac ● Tachycardia, palpitations, wide pulse pressure, afib ■ Swelling of hands and feet ■ Thyroid acropachy (Clubbing of fingers & toes) ■ Vitiligo ■ Brisk reflexes and accelerated w/ accelerated relaxation phase ■ Weakness of the proximal muscles ● Lid lag ■ Ophthalmopathy ● Blurred vision, dry eye syndrome, diplopia ● Periorbital edema ■ Men w/ Graves ● Gynecomastia, reduced libido & erectile dysfunction ○ Diff Dx ■ Toxic multinodular goiter or adenoma ■ Thyrotoxic phase of autoimmune Hashimoto’s ■ Subacute thyroiditis ● Postpartum ● Painful ● Drug induced (lithium, amiodarone) ■ Excess ingestion of Levothyroxine ■ Secondary to elevated human chorionic gonadotropin hCG ● Multi-gestational ● Gestational trophoblastic disease ○ Diagnostics ■ TSH→ Suppressed ■ Free T4 & free T3 or total T3 ● Elevated ■ Thyrotropin receptor antibodies (TRAbs) - Highly suggestive of Graves ● Positive in 98% of pts w/ untreated Graves ● Helps confirm dx ● ESR, CBC, LFTs ○ ESR elevated if it’s more of a subacute thyroiditis ○ LFTs elevated, alk pho elevated ■ Thyroid stimulating immunoglobulins (TSI) ● May be positive but less sensitive & negative result does not exclude Graves dz ■ Radioactive Iodine Uptake Scan ● Radionuclide is given PO or IV, thyroid scan 6-24 hrs later ○ Done in nuclear medicine ● Homogenous increase in the uptake of iodine ● If it’s toxic multinodular→ multiple localized areas of uptake ● Do NOT do in preggo pts ■ Thyroid Ultrasound ● If there’s an abnormality on exam ex. Nodules ● In pts w/ contraindications to uptake scan

○ Based on size and pattern ■ FNA Indications: ● Nodes > 1cm w/ high risk hx ● Solid nodes > 1cm that are hypoechoic ● Complex (solid & cystic components) > 1.5 cm w/ any suspicious US features ■ PET scan ● Highest resolution for detection of aggressive metastatic thyroid cancer lesions ○ IDs differences in how quickly cells metabolize glucose ■ Cancer cells metabolize glucose more quickly than normal cells ○ Diff dx ■ Benign vs malignant ● Benign- cysts ○ Soft, typically less than 1 cm ○ 90% of nodules are not malignant ● Malignant - adenomas ○ Hard, firm nodule ○ 10% of nodules are malignant ○ Cure rate for thyroid malignancy is high ● Autoimmune thyroid conditions ex. Hashimoto ● Cysts of parathyroid glands need to be r/o ■ Brachial anomalies ■ Thyroglossal duct cyst ■ Lymphadenopathy ■ Neck abscess ■ Parathyroid hemorrhage ● Less common ○ Management of Benign Nodules ■ Repeat exam, US & TSH in 12 mo ● If unchanged, repeat @ 24 mo ● Consider repeating fine needle aspiration (FNA) if increased more than 50% ■ Surgery if large size (>4 cm) or symptomatic ● Complications from surgery include hypoparathyroidism & hoarseness from recurrent laryngeal nerve damage ○ Management for pts tx for thyroid ca ■ On thyroid replacement life long ● These pts probably had a thyroidectomy ● TSH should be suppressed to prevent more thyroid stimulation ○ Goal : < 2 ● Thyroglobulin levels followed ● Pts w/ differentiated thyroid ca are followed closely for the 1st 5 years and then 6-12 mo intervals Hyperparathyroidism ● Overview ○ Located on the posterior aspect of the thyroid gland ■ 4 lil beans on the back ○ Gland sense and regulate calcium ■ Parathyroid hormone causes an increase in calcium levels by telling the bones hey we need some Ca if ya know whatta mean. ■ Then they tell the kidneys hey can you hold on to that sweet Ca? ■ Then they say hey intestines here’s some Vit D to help absorb Ca ○ Most common cause is a benign growth on one of the glands ■ Increases the amount of parathyroid hormone ■ Hyper more common than hypoparathyroidism ● Primary most common ○ Due to growth on gland causing greater release of parathyroid hormone (PTH)→ increasing Ca levels in the bod ■ Single adenoma ○ More common in women, pts > 60 yo ■ RF- exposure to ionizing variation ● Can occur due to a familial disorder ex. Multiple endocrine neoplasia

■ Benign account for 10-15% of intracranial masses ■ Microadenoma < 1 cm ■ Macroadenoma > 1 cm ○ Majority of pituitary adenomas are prolactinomas ■ Secrete prolactin, between 40-57% are these type of tumors ○ Growth hormone secreting tumors ■ Account for 11% ○ ACTH secreting hormones → cause Cushing dz ■ 2% of pituitary adenomas are ACTH secreting ● S/S ○ Depends on what hormone is secreted by that tumor ■ Type of tumor is determined by what hormone it’s secreting Cushing Disease ● Elevated Cortisol Levels ○ Caused by an increased production of ACTH from the anterior pituitary→ stimulates the adrenals to produce cortisol → Cushing syndrome ■ Direct production of cortisol from the adrenals can also cause Cushing syndrome ○ Most common cause is exogenous steroids ■ Ex. Long term use of prednisone ● More common in women ● Peak incidence between 50-60 yo ■ Endogenous→ excess ACTH from pituitary tumors or adrenal gland hyperproduction ● S/S ○ Obesity, HTN, glucose intolerance ○ Hirsutism, moon face ○ Purple Striae, bruising, “senile” purpura on hands, acanthosis nigricans ○ Menstrual irregularities, Galactorrhea ■ Menses irregular due to decrease in LH & FSH ● Loss of menses ○ Decreased libido, muscle weakness & wasting, insomnia ○ Poor short term memory, HA ○ *Buffalo Hump* ← Classic symptom! ○ In kids → depressed linear growth & excess wt gain ● Diff Dx ○ Pseudo-Cushing ■ Possible due to alcohol abuse ■ Usually resolves once pt stops drinking ■ Normal clinical & lab findings ○ Exogenous corticosteroid use ■ When using steroids for more than 10-14 days as part of management of asthma, difficult dermatitis problems, rheumatic dz, malignant neoplasms carefully monitor to detect early, persistent endogenous corticosteroid suppression ○ Adrenal cortical adenoma or carcinoma ■ Small cell lung ca ○ Ectopic adrenocorticotropic hormone (ACTH) ○ Ectopic corticotropin-releasing hormone (CRH) ○ Eating disorder ■ Increase cortisol levels ○ Poorly controlled DM ■ Cortisol increases blood sugar ○ PCOS ● Dx ○ Always do testing in absence of acute illness! ○ Initial testing, one of the following: ■ 24 hr urine free cortisol 2xs → > 100mcg of cortisol ■ Late night salivary cortisol 2xs ● Preferred method, very sensitive, easy to do ■ Low dose dexamethasone suppression test ● Pt takes a low dose of dex @ night around 11p.

● Pt then comes in for blood draw & cortisol level ● In a healthy pt cortisol is suppressed, pt w/ cushing dz will not have suppressed cortisol ○ Refer to endo: ■ If initial testing is + ■ If high clinical suspicion & test is - ■ If pt has Cushing syndrome ● Tx → depends on the source of the hypercortisolism ○ Pituitary tumor resection is 1st line when indicated ○ Transsphenoidal surgery ○ Medications for pts who are not surgical candidates ■ Possible along w/ radiation ○ Recovery from iatrogenic suppression of cortisol production can take 6-9 mo ● Complications ○ Osteoporosis ■ Get a bone density measurement, esp w/ concurrent conditions that have an impact on bone ex. Thyroid replacement tx and menopause ○ Risk of infection, HTN, DM Pituitary Prolactinoma ● Overview ○ Most common pituitary adenoma ■ Micro or macro adenoma ■ More common in women btw 20-50 yo ● Usually present w/ menstrual irregularity or galactorrhea ■ Secretes excess prolactin hormone ○ Assoc. w/ hereditary multiple endocrine neoplasia ○ Symptoms differ btw M & F ● Both sexes s/s ○ Infertility, loss of interest in sex ○ Low bone density, HA ○ Visual disturbances ○ Delayed puberty ● Females ○ Oligomenorrhea or amenorrhea ○ Galactorrhea ○ Vaginal dryness, Hirsutism ● Males ○ Erectile dysfunction, gynecomastia ○ Decreased body & facial hair ● Diff dx ○ Pregnancy, Lactation ■ Prolactin elevated in pregnancy & lactation ○ Compressive “stalk” effect from another tumor ○ Meds ■ Antipsychotics often cause hyperprolactinemia & cause galactorrhea in women ■ Ca channel blockers, tricyclics, Opioids ○ PCOS ■ Similar symptoms ○ Renal dz, primary hypothyroidism ○ Recent food consumption ■ Can cause the prolactin level to be transiently elevated ● Exam ○ Ophthalmic exam ○ Neuro exam ■ Check for visual field defect ● Some tumors can impinge on optic apparatus ○ Skin ■ Hirsutism→ Acne, hair growth ○ Thyroid

■ Check for goiter ○ In kids ■ Assess for pubertal changes ■ Look for evidence of hypogonadism ■ Assess breasts on both sexes! ● Look for gynecomastia & galactorrhea ● Dx ○ Prolactin hormone ■ If elevated and asymptomatic, repeat in the morning ■ Prolactin level correlates w/ size of adenoma ● Bigger the tumor→ higher the prolactin level ○ Rule out other causes ■ Kidney disease, pregnancy, hypothyroidism ■ Liver disease or hepatitis ○ BUN, Creatinine ○ Hcg if childbearing female ○ TSH/free T4 ○ ALT/AST ○ Once you’ve r/o other causes w/ elevated prolactin level → Get an MRI! ■ Determines size of adenoma ● Management ○ Endocrine referral ○ Ophthalmology referral ■ For more thorough neuro-ophthalmology exam ○ Tx if symptomatic or macroadenoma ■ Dopamine agonists ● Cabergoline & Bromocriptine ○ Carbergoline preferred bc it has fewer side effects & greater efficacy ● Respond quickly to med ■ Don’t need to treat asymptomatic w/ microadenoma ■ All MACROadenomas must be treated ○ Monitor prolactin level ■ Frequently in the beginning, less frequently as time goes on ○ Repeat MRI ■ To check the adenoma is decreasing ○ After a couple of years, some pts may be able to come off of meds if prolactin level is normal and MRI is normal Why Diabetes is the dark side of the force ● It’s the leading cause of CVD, Renal Failure, Blindness & nontraumatic lower limb amputation ○ Risk of microvascular damage → retinopathy, nephropathy & neuropathy ○ Increased risk of macrovascular damage → Ischemic Heart Dz, stroke, PVD Pathophysiology of Diabetes ● Type 1 ○ Destruction of the beta cells in the islets of Langerhans on the pancreas ■ Immune-mediated response ● Autoantibodies that are responsible for this destruction ■ Rate of destruction is variable ● Presenting symptoms can be long, slow presentation vs something that happens quite quickly ■ Genetic predisposition ● All pts w/ this type require insulin bc their pancreas is no longer producing the hormone ■ Catabolic disorder, absolute lack of insulin → breakdown of body fats & proteins → diabetic ketoacidosis ● DKA leads to dx ○ No single factor has been implicated in development of T1 ■ Proposed contributing factors: ● Viral infection ex. Coxsackie ● Exposure to certain environmental antigens or toxins ● Genetic predisposition to T1 w/ offspring of moms who have T1 @ approx 10 fold risk, fathers 20 fold risk

○ Often seen in kids or adolescents but can have a latent onset in adults ○ Less common than type 2, about 5% of DM cases ● Type 2 ○ 90-95% of DM cases ○ Relative insulin ■ May have a deficiency but it’s more of an issue of insulin resistance ■ Can happen in adults who are overweight but can also happen in kids ■ May lead to requiring insulin ● Beta cells be tired and stop working ○ DM Factors ■ Genetic and environmental impact ● Genetic ○ Making insulin but not releasing it appropriately → increase in hepatic glucose output → increases amount of circulating glucose → T2DM ● Environmental ○ Obesity→ leads to insulin resistance → decreased glucose uptake in the skeletal muscle → more free glucose & hyperglycemia → T2DM ○ Pathophysiology Core defects ■ Decreased incretin effect ● Decrease in GLP-1 hormone & GIP → decreased stomach secretion of ghrelin → higher glucose levels in the body ■ Neurotransmitter dysfunction→ altered insulin signaling→ ultra lipid sensing→ raise blood sugar ■ When muscles become resistant to insulin → decreased glucose uptake in muscle → accumulation of glucose→ hyperglycemia ■ Kidneys ● When glucose levels are high → increased glucose reabsorption & gluconeogenesis → more sugar in the body ■ Increased hepatic glucose production→ increased glucose ■ Decrease in ability of the cells to uptake glucose → Increased lipolysis→ inflammation → high glucose levels ■ Pancreas ● Beta cells → decrease in cells → decrease in insulin secretions ● Alpha→ increased glucagon secretion→ hyperglycemia ● Diagnostic criteria for DM in non-pregnant adults ○ Fasting plasma glucose >/= 126 mg/dL ; fasting - no food for @ least 8 hrs ○ Oral Glucose tolerance test (OGTT) (75 g anhydrous glucose) w/ plasma glucose > 200 mg/dL 2 hours post glucose load ○ HgbA1c >/= 6.5% ■ Some POC assays are specifically approved for dx but POC A1c testing is not recommended to dz DM ■ A1c may not be accurate in pts w/ anemias or hemoglobinopathies due to the rapid RBC turnover ■ Use blood glucose values for dz in pts w/ altered RBC turnover ● Preggo women in 2-3rd trimester, recent blood loss or transfusion, those on erythropoietin tx, those on hemodialysis ○ **Random glucose >/= 200 mg/d L & classic s/s of hyperglycemia or hyperglycemic crisis (polyuria, polydipsia or unexplained wt loss) ■ This is the only test that can be dx of DM alone! ■ Serum glucose is not the same as “plasma glucose” ● The dx criteria is based on plasma glucose ● Serum can vary by as much as 10-20% compared w/ 1-3% for plasma glucose ○ **MUST HAVE TWO OF THE CRITERIA MET IN ORDER TO DIAGNOSE EXCEPT FOR THE RANDOM W/ S/S** ■ Recommended plasma blood glucose be used to dx acute onset of T1DM in pts w/ s/s of hyperglycemia

● ● Screening Tests ○ A1C, Fasting glucose, OGTT ■ A1c may have some advantages, such as convenience & less day to day variation but must be balanced by costs and availability of A1C testing & lower sensitivity of the test ○ Who should you test for preDM or DM in asymptomatic adults? ■ ALL adults starting @ 45 yo regardless of wt ■ Adults who are overweight → BMI >/= 25kg/m2 & have other risk factors : * *Asian pts w/ BMI >/= 23kg/m2* * ● High risk ethnic pops ex. AA, Hispanic, American Indian, Alaska Native, Asian American, Pacific Islander ● 1st degree relative w/ DM ● Hx of GDM or giving birth to a bb > 9 lbs ○ GMD occurs in approx. 7% of preggo pts in the US & risk of developing T2 is highest in the decade immediately following delivery!! ● Physical inactivity ● HTN (BP > 140/90) or tx for HTN ● HDL < 35 ● Fasting TG > 250 ● Women w/ PCOS ● Previously noted A1C > 5.7%, impaired glucose tolerance (IGT) (glucose 140-199 2hrs after OGTT) or impaired fasting glucose (IFG) on previous testing ● Other clinical conditions associated w/ insulin resistance (ex. Acanthosis nigricans, non alcoholic steatohepatitis, PCOS & small for gestational age birth wt) ● Hx of CVD ● Tx w/ atypical antipsychotics or glucocorticoids ■ If none of the above are met→ start screening @ 45 yo ■ Normal results? Test again Q 3 yrs, consider more frequent testing depending on initial results & risk status ○ Who should you test for preDM or Dm in asymptomatic kiddos? ■ 2020 ADA guidelines recommend in kids who meet the following: ● Overweight (BMI > 85th % for age & sex, wt for ht > 85th %, or wt > 120% of ideal for ht) ○ AND who meet one or more of the following criteria: ■ Maternal hx of gestational diabetes mellitus (GDM) during the pt’s gestation. ■ Family hx of T2DM in 1st- or 2nd-degree relatives ■ High-risk race/ethnicity (same groups as for the adults, ex. Native American, AA, Latino, American, Asian American, & Pacific Islander) ■ S/s of insulin resistance or conditions assoc. w/ insulin resistance (ex acanthosis nigricans, HTN, dyslipidemia, PCOS, or small-for-gestational-age birth wt) ○ Dx Criteria for PRE -Diabetes:

● Pts w/ impaired fasting glucose (BS 100-125 mg/dL) OR ● Signs of insulin resistance (metabolic syndrome) ○ *Note: HLD is assoc. w/ metabolic syndrome & obesity but does NOT cause preDM* ● A1c > 5.7% ○ Test yearly! ■ This condition reflects worsening pancreatic beta cell function ● Most common cause of preDM is obesity ● Chronic pancreatitis & chronic steroid use may also impair glucose metabolism ● 4 Clinical Classifications of DM 1. Type 1 a. Immune mediated DM w/ evidence of autoimmune β-cell destruction, typically leading to absolute insulin deficiency. i. There is some controversy over whether or not latent autoimmune diabetes of adults (LADA) warrants its own designation; in the current ADA, this condition is considered a slow-onset type 1 diabetes mellitus b. Idiopathic T1 - unclear etiology i. These pts are insulinopenic & prone to DKA but lack evidence of B-cell autoimmunity 2. Type 2 a. Typically a multifactorial process, including relative insulin insufficiency (the pancreas does release enough insulin), insulin resistance, & often unregulated gluconeogenesis in the liver (producing glucose in the face of hyperglycemia) 3. Gestational DM (GDM) a. Dx during the 2nd or 3rd trimester of pregnancy that was not clearly present prior to gestation 4. Other a. Monogenic diabetes syndromes. Ex. neonatal diabetes & maturity-onset diabetes of the young (MODY) b. Dz of exocrine pancreas ex. Cystic Fibrosis c. Pancreatic insufficiency 2ndary to chronic/recurrent pancreatitis d. Drug/chemical induced ex. Pts treated w/ glucocorticoids & those tx for HIV/AIDs or after organ transplantation ● Testing in T1 DM ○ In the absence of unequivocal symptomatic hyperglycemia, a dx of T1DM should be confirmed by repeated measurement of the same test on a subsequent day. ■ Mild signs and symptoms of T1DM may be present months prior to acute clinical presentation, and because it is preferable to dx T1DM prior to metabolic deterioration into DKA, clinicians should keep T1DM on the diff dx for many common presenting complaints. ■ Further investigation may be prompted by glucosuria present on a UA, (serum glucose > 180 mg/dL causes spilling of glucose into urine) young girls w/ candidal vaginitis in absence of other risk factors, kids who complain of blurry vision, enuresis, or lack of weight gain. ○ To confirm Dx : Check for the presence of islet cell autoantibodies (ICAs), insulin autoantibodies (IAA) or autoantibodies to glutamic acid decarboxylase 65 (GAD65) , the tyrosine phosphatases IA-2 transmembrane proteins or the zinc transporter (ZnT2) ■ 70-80% of T1 have anti-GAD antibodies ● More likely to be present in young adults ■ Adding ICA can increase sensitivity of detection of T1 ■ Anti insulin antibodies may be less helpful ● Must check in pts before they receive exogenous insulin to be valid ● More likely to be present in young kiddos ○ Screening for other autoimmune dz ■ Thyroid dz & celiac dz ■ Pts w/ T1 could have Hashimoto’s, Graves, Addison, autoimmune hepatitis, dermatomyositis, myasthenia gravis, vitiligo & pernicious anemia (B12 def.) ● Screening is not recommended for these due to rare instances ● Clinical Presentation & Physical ○ S/S ■ May be asymptomatic or develop only subtle symptoms that may persist for weeks, mos, years before detection ■ Polyuria, polydipsia, polyphagia, wt loss, blurred vision, fatigue, slowly healing wounds, frequent infections. ■ Numbness & tingling of the feet & hands ○ Signs of Ketoacidosis ■ N/V, abd pain, rapid shallow breathing, hypotension & dehydration

○ Physical ■ Appears dry & flushed ■ Assess skin, eyes, heart & lungs ● Eyes look for hemorrhages or exudates ○ Remember the cotton woolies! ■ Palpate thyroid esp in T1 ■ Look for early evidence of vascular & neuropathic complications. ● Pharmacology ■ DPP-4s (-Gliptin) ● Affect the liver, pancreas, stomach ● Block DPP4 enzyme which destroys incretin ○ Incretin helps body regulate insulin, prolonged incretin levels → increased secretion of insulin, suppresses glucagon ○ Blocking DPP4 leads to more insulin availability to decrease glucose ● Wt loss or weight neutral ● SE: Pancreatitis, hypersensitivity reactions, hypoglycemia if used in conjunction with sulfonylureas; fatal hepatic failure; possible worsening of heart failure; possible & severe joint pain ■ GLP-1s (-Tides. Ex Exenatide - Byetta ) ● Affect liver, pancreas, brain, stomach ● Mimic natural effects of incretin ○ Allows greater production of insulin ● These are injections! Can aid in wt loss ● Can reduce death from certain CV causes ● SE: N/V/D, renal impairment, AKI assoc. w/ dehydration caused by GI toxicity; injection-site reactions; risk of acute pancreatitis; thyroid C-cell hyperplasia; possible risk of thyroid C-cell carcinoma ■ Biguanides ( Metformin ) ● Affect liver exclusively ● Increases peripheral glucose uptake → improves insulin sensitivity → decreases hepatic glucose production & intestinal absorption of glucose ○ Help liver convert fats → activates AMPK → helps cells respond to insulin ● Weight neutral or modest wt loss ● Can reduce A1C 1-1.5%! Yay! ● SE: metallic taste, nausea, diarrhea, abdominal pain, lactic acidosis (rare – but potentially fatal); B12 deficiency ● Contraindicated in pts w/ GFR < 30 as well as: ○ Pts predisposed to develop Lactic Acidosis ○ Pts w/ decompensated CHF ○ Liver failure ○ Heavy alcohol use ○ Undergoing major surgery ● *Stop this med when undergoing imaging w/ iodinated contrast & do not restart for 48 hours & renal function ok* ● Consider periodic testing for vit B12 deficiency as it is associated w/ b12 deficiency ○ Especially consider in pts w/ anemia or s/s of peripheral neuropathy ■ Thiazolidinediones (-Azones ex Pioglitazone ) ● Affect fat cells and skeletal muscles ● Increases insulin sensitivity by improving insulin action in the cell ○ Increase utilization of available insulin via liver, muscle and FAT tissue ○ Decreases hepatic glucose production ● *Wt gain* ● SE: Increased risk of CHF (& possibly CAD); peripheral edema; macular edema; weight gain; possible decrease in bone mineral density/increased incidence of fractures in women; hepatic failure; possible bladder cancer risk ■ Sulfonylureas (-zides ex. Glipizide ) ● Works in the pancreas ● Causes beta cells to secrete more insulin!! ○ Once beta cells are completely tapped out, sulfonylureas will no longer be functional ● Glyburide → wt gain!

● SE: Hypoglycemia (particularly in the oldies or in pts w/ renal impairment); wt gain; possible aggravation of myocardial ischemia ■ Non-Sulfonylurea Secretagogues ( Repaglinide & Nateglinide ) ● SE: Hypoglycemia; weight gain; partly metabolized by CYP3A4 (therefore levels are increased by macrolides which inhibit the enzyme and decreased by rifampin, which induces the enzyme) ■ Selective Sodium Glucose Cotransporter 2 Inhibitors (SGLT-2) ● -Flozin drug names ex Canagliflozin ● Works in the kidneys ○ Help to decrease the renal tubular glucose reabsorption ○ Causes more excretion of glucose through the kidneys ○ Does NOT cause any hypoglycemia as it does not stimulate insulin release ● Shown to reduce CVD ○ Some proved efficacy for primary and secondary prevention of CV endpoints, their cardioprotective effects are most pronounced in pts w/ underlying CVD ● SE: Genital mycotic infections, volume depletion; decreased eGFR; AKI; hypotension; fractures; hyperkalemia; hypermagnesemia, hyperphosphatemia; euglycemic diabetic ketoacidosis ● BBW→ Fourner’s Gangrene→ necrotizing fasciitis ■ Alpha-Glucosidase Inhibitors ex. Acarbose ● Inhibits alpha-glucosidase enzymes in the small intestinal brush border, which interferes w/ carb digestion & slows absorption of glucose & other monosaccharides ● SE: Abd pain, diarrhea & flatulence--due to osmotic effects & bacterial fermentation; transaminase elevations; fatal hepatic failure ● Contraindicated in pts with chronic intestinal diseases ■ Amylin Agonist ( Pramlintide ex. Symlin) ● Can result in modest wt loss or at least wt neutral ● Injection! ● SE: N/V, HA, anorexia, severe hypoglycemia when given w/ insulin ■ Bile Acid Sequestrants (Colesevelam) ● SE: constipation, nausea, and dyspepsia; increased triglycerides; interference with absorption of oral drugs ■ Bromocriptine ● SE: N/V, fatigue; HA, dizziness; somnolence; syncope ○ Insulins! ■ Normal physiologic insulin in NONdiabetics → 20-40 units in 24 hrs ■ Insulins may be used as 1st line tx in T2 DM if: ● A1C > 10% or glucose range > 250 ● Severe illness w/ assoc complications ● Gestational DM ● Fragile old pts ■ Total daily dose (TDD) 0.5U/kg adjusted for sensitivity or resistance to insulin ● 50% is typically basal, 50% divided between 3 meals ■ Rapid Acting → Lispro (Humalog), Aspart (Nvolog), Glulisine (Apidra) ● Onset: 5-15 min ● Peak: 30-60 min ● Duration: 4-6 hours ● 1 unit per 2 g of carbs in insulin-resistant pt ● 1 unit per 30 g of cars in insulin-sensitive pt ■ Short Acting → Regular (Humulin R, Novolin R) ● Onset 30-60 min ● Peak 2-3 hrs ● Duration 8-10 hrs ■ Intermediate Acting → Isophane (NPH, Humulin N, Novolin N) ● Onset 2-4 hours ● Peak 4-10 hours ● Duration 12-18 hours ■ Long Acting “Basal Insulin” ● Glargine (Lantus, Basaglar, Toujeo) ○ Onset 2-4 hours, NO peak, Duration 20-24 hrs ● Detemir (Levemir) ○ Onset 2-4 hrs, Peak 3-9 hours, Duration 6-24 hrs

○ More effective when it is used twice daily, effectiveness seems to decrease after about 12 hrs ● Degludec (Tresiba) ○ Onset 1 hour, Peak 9 hours, Duration > 42 hrs ● Adjust basal q 2-3 days until fasting BS is consistently w/in target range ○ Increease by increments of 2-5 U in an obese or insulin resistant person ○ Increase by 1-2 U in pts w/ thin body frame & in pts w/ frequent eps of hypoglycemia ○ Fasting < 80? Reduce in increments Q 2-3 days ■ Premixed: → 70% NPH/30% Regular Insulin Humulin 70/30 ● Onset 30-60 min, Dual Peak, Duration 10-16 hrs ■ Mealtime insulin is injected no more than 10 min before eating! ■ Frequent glucose monitoring is recommended after a change in insulin product or concentration as dose adjustments may be necessary ■ **Insulin tx is associated w/ wt gain of 1-3 kg!** ○ What med should your patient start? Based on AACE 2020 Algorithm ■ Pts w/ T2 w/ initial A1C < 7.5% → Monotherapy for 3 months! ● Can choose from Metformin, GLP1, SGLT2, DPP4, TZDs, AGIs, or Sulfonylureas (SUs) ● ***Pts who are high risk per ASCVD calculation, CKD stage 3 or HF w/ reduced EF → Long acting GLP1 or SGLT2** ● Been 3 mo & their hemoglobin isn’t < 7%? → DUAL Therapy! ■ A1C > 7.5%? → DUAL Therapy ■ A1C not < 7.5 after 3 months on dual? → Triple Tx! ● Or insulin ■ A1C > 9% right off the bat? → Insulin w/ow/o other meds ● Especially if the pt has s/s of DM ■ Most PCPs start pt on Metformin, GLP1 or SGLT2 ● Less evidence for monotherapy with other meds ■ Insulin Recs ● AACE/ACE algorithm recommends starting w/ a basal insulin ○ A1C < 8% → total daily dose (TDD) = 0.1-0.2 U/kg ○ A1C > 8% → TDD = 0.2-0.3 U/kg ○ Stop sulfonylurea therapy or reduce once starting basal insulin Care of Diabetic Patient - Diabetic Foot ● MIcrovascular complications 1. Diabetic retinopathy - changes of the eye 2. Diabetic nephropathy - Kidney damage 3. Diabetic neuropathy - changes to peripheral nerves ■ Peripheral nerve damage to lower extremities ■ Person loses sensation in the foot, sometimes higher up in the lower extremity ■ Signs of neuropathy ● Pins & needles feelings, sensation goes up to the foot ● Caring for diabetics *****A1C goal: < 7%!!!!***** ○ Regular check ups, Q 3 mo for pts who are not at goal or changing tx! ■ Q 6 mo in stable DM pts ● Note: Goal in kids < 7.5%! ■ Require patient to take off their shoes every visit ■ Fasting & preprandial BS goal → 70-130 ■ Postprandial < 180 mg/dL ○ Diabetic foot exam once a year ○ Diabetic eye exam once a year ○ Check for microalbumin in the urine once a year ■ MIcroalbumin indicates diabetic nephropathy ● Foot exam ○ Done @ least annually for those w/ T2 & started w/in 5 yrs of dx in T1 ■ Pts w/ insensate feet, foot deformities or ulcers should have their foot checked @ every visit ○ Risk of diabetic foot ulcers ■ Loss of sensation in the foot→ cut or something on the foot like a pebble → open ulcerated area ○ Take off yo shoes! ○ Look at their ENTIRE FOOT all the way around

■ Is the skin intact? Pink, dry & warm? ■ Any open sores or wounds that may be concerning? ■ Check for pulses ○ Use a monofilament to check for sensation ■ Little filament you poke the foot with ● Feels like a really thick fishing line, not painful but it provides the same amount of pressure on each spot ● Great way to assess for neuropathy ■ Have patient close their eyes ● Poke each toe, 10 places total ● Check along the ball of the foot, top of the toes ○ Heels may have decreased sensation due to callus ● Every time you poke, they should say yes or no ○ Record how much they felt 0-10, lower score indicates more severe neuropathy ○ In addition use temperature, vibration using 128 Hz tuning fork, pinprick sensation & ankle reflexes ● Screening for Retinopathy ○ Dilated retinal exam done @ time of dx in all pts w/ T2 & those > 10 yo w/ T1 for 5 or more years ○ If no retinopathy present after serial annual exams, rec screening intervals may increase to no longer than Q2 years ● Screening for Nephropathy ○ Diabetic nephropathy occurs in 20% to 40% of pts w/ DM & is the leading cause of ESRD ○ Serum creatinine at least annually to allow calculation of the GFR ○ Urine albumin excretion annually in all persons with T2DM & in those w/ T1DM who have had the dx for 5+ years. ○ This is done easiest w/ a spot urine-to-creatinine ratio, recommended at least annually. ■ Note: The terms “microalbuminuria” & “macroalbuminuria” are no longer used; instead the term persistent albuminuria will be used for patients whose albumin exceeds the “normal” amount (which is less than 30 mg/24 h). ○ Persistent albuminuria is a marker for CVD. Several authorities recommend that persons w/ DM & persistent albuminuria have additional cardiac evaluation. ● Immunizations ○ PNA vaccine – the immunization recommendations were revised in 2015 to reflect recent CDC guidelines regarding PCV13 & PPSV23 immunizations in older adults. ■ Patients age 2 to 64 years old w/ DM should receive a PPSV 23 vaccine. ● If < 65 when vaccine is given, repeat after age 65 w/ @ least 5 yrs btw doses. ■ If > 65, one vaccine is sufficient--unless there is also a hx of nephrotic syndrome, CKD, or other immunocompromised states, such as post-transplantation. ■ Adults who are 65 years + & who have not previously received PCV13 should receive a dose of PCV13 first , followed 6 to 12 mos later by a dose of PPSV23. ○ Flu vaccines should be given annually to all persons with DM > 6 mo. ○ Hepatitis B vax should be given to unvaccinated adults w/ DM age 19 to 59 yo ■ Consider giving Hepatitis B vax to unvaccinated adults > 60 years ● Tobacco Use ○ Smoking cessation counseling & discuss use of pharm agents to help smoking cessation ● Aspirin/antiplatelet agents ○ Aspirin 75 to 162 mg/day ■ Secondary prevention in those w/ Dm & Hx of CVD ■ Primary prevention in pts > 50 yo & older w/ T1 or T2 or who have additional CV risk factors ■ *No evidence of benefit for those < 30 yo ● Contraindicated in those < 21 yo because of risk of Reye ○ Clopidogrel (75mg/day) subbed for anti plt tx for those w/ allergy to aspirin ● Blood Pressure ○ Measure at every visit! ○ Goals: ■ ADA guidelines: Adults < 140/90 ● Lower SBP < 130 may be appropriate for certain individuals such as younger pts if can be achieved w/o undue tx burden ■ Kids < 130/80 OR < 90th % for age, sex & ht ○ Start meds if lifestyle mods do not lower BP to target ■ ACEI, ARBs, CCB or diuretics are recommended ● **NOT IN PREGGO WOMEN! ■ Give 1 antiHTN med @ night

○ Baseline ECG after age of 40 ● Cholesterol ○ Get a lipid profile @ time of dx & @ least Q 5 yrs in pts under 40 yo! ■ Based on guidelines a calculated ASCVD score of > 20% and the pts age (> or < 40 ) is what primarily drives the decision to tx w/ statins ○ LFT annually, more frequent if abnormal ● Screen for diabetic gastroparesis w/ hx ○ If suspicious, gastric emptying study is recommended ● Education ■ Tell them to look at those stanky feet erry day ■ Look for any open cuts or wounds ● Wounds aren’t going to heal as well due to poor perfusion ○ There’s more sugar in the blood → sluggish blood flow ● Little wounds can quickly become big things ○ Pts w/ neuropathy aren’t even aware of it ■ Lifestyle changes ● Adults w/ IFG or IGT loss > 5% of body weight, increase exercise to 30 min a day on most days of the week ○ Wt loss of 4kg has shown to improve glucose control ● Exercise causes increased insulin sensitivity contributing to exercise lag effect → can last up to 48 hours after exercise ● Kids w/ preDM and DM should be encouraged to engage in physical activity @ least an hour a day! ■ Nothing reverses neuropathy ● Keep a good tight glycemic control to prevent it ● Keep A1C < 7 to prevent microvascular complications ■ Bariatric surgery considerations in DM pts ● Pts w/ T2 who cannot achieve durable wt loss or improvement in comorbidities w/ reasonable non surgical tx. w/ BMI as low as 30 **27.5 in Asian American ● Surgery which results in sustained wt loss of > 20kg may eliminate the need to take meds for DM ■ ● Screening Recommendations for T1 DM for prevention of micro & macrovascular complications ○ NEPHROPATHY: ■ Annual screening for albuminuria w/ a random spot urine sample for albumin/creatinine ratio after the child is 10 years old or older and has had DM for @ least 5 year s. Normal spot albumin/creatinine ratio is </= to 30 mg/dg. ○ RETINOPATHY: ■ Annual comprehensive & dilated eye exam after age 10 & when child has had T1DM for @ least 3 to 5 years . ○ NEUROPATHY:

■ Annual compressive foot exam starting @ age 10 or after puberty has started (whichever is earlier) after DM duration of 5 years. ○ HYPERTENSION: ■ BP @ time of dx & every office visit thereafter. Elevated BP should be confirmed on 3 separate days. ○ DYSLIPIDEMIA: ■ Fasting lipid panel starting @ age 10. If (LDL) cholesterol is < 100 mg/dL, then repeat every 3 to 5 years. ● If abnormal, monitor yearly. ● Initial therapy should consist of optimizing glucose control & medical nutrition therapy using a Step 2 American Heart Association (AHA) diet. ● Statin therapy is recommended after making lifestyle changes if LDL cholesterol is > 160 mg/dL, or >130 mg/dL with 1 or more CV risk factors. ○ Statins contraindicated in preggo! So consider birth control in adolescents who require statin tx. ○ THYROID DISEASE: ■ Screen for thyroid dz w/ TSH soon after dx & improvement in glucose control. ■ Consider testing for antithyroid peroxidase & antithyroglobulin antibodies soon after dx. ● If TSH is normal, repeat every 1 to 2 yr s, or sooner if pt has symptoms of hypothyroidism, thyromegaly, abnormal growth rate, or unexplained glucose variation. ○ CELIAC DISEASE: ■ Screen for Celiac w/ either tissue transglutaminase or deamidated gliadin antibodies, along with serum immunoglobulin A (IgA) level, soon after dx. ■ Recommendations for screening also include if the patient has a 1st degree family member w/ celiac, growth failure, wt loss or failure to gain wt, GI symptoms (diarrhea, flatulence, abd pain, or other concerns for malabsorption), or recurrent unexplained hypoglycemia or worsening of glycemic control. Uh Oh She pregnant, now she might have gestational DM ● Measure fasting glucose, random glucose or A1C for high risk women prenatal visit ○ Fasting plasma glucose 92-125 = GDM ○ < 92? Recheck at 24-29 wks gestation w/ OGTT ● Dx ○ ● Maternal Complications of DM ○ Cesarean delivery ○ Hyperglycemia, ketoacidosis ○ Hypoglycemia ○ Pregnancy-induced hypertension ○ Pyelonephritis, other infections ○ Polyhydramnios, Preterm labor. Spontaneous abortion ○ Worsening of chronic complications (retinopathy, nephropathy, neuropathy, cardiac disease) ● Neonatal complications of moms w/ DM ○ Birth trauma ○ Congenital anomalies (especially cardiac malformations and neural tube defects) ○ Hyperbilirubinemia, Hyperinsulinemia ○ Hypertrophic cardiomyopathy, hypoxia ○ Hypocalcemia, Hypoglycemia, Hypomagnesemia ○ Left colon syndrome, Macrosomia

○ Neurologic instability, irritation ○ Polycythemia, Renal vein thrombosis ○ Stillbirth ● **Women who had GDM carry a 40-60% chance of developing T2DM in 5-10 yrs ○ Likelihood of GDM w/ future pregnancies, increased risk of CVD ● Women w/ T1DM ○ 1 in 10 chance of congenital anomaly developing in growing fetus in setting of poor glycemic control ○ 1st trimester insulin doses may be lower due to increase in fetal glucose transport ○ Insulin resistance later from placental hormone, prolactin & cortisol ■ Plateau’s around week 36 ● Women w/ T2 DM ○ Delay conception until A1C < 7% ○ Below 6,5 reduces risk of anomalies ex. Congenital heart dz, miscarriage, anencephaly, microcephaly ○ D/C sulfonylurea before labor and delivery to prevent hypoglycemia ○ MOnitor Blood glucose 4xs + a day, exercise Indications for Referral or Hospitalization ● Refer ○ New DX of T1 ○ Poorly controlled T2DM despite 2 or more meds ○ DM complication ○ Initiating insulin pump or other intensive insulin tx ○ After hospitalization ● Hospitalize ○ Acute metabolic complications ○ DKA or HHS ○ HYpoglycemia w/ neuroglycopenia ■ BS < 50 that does not respond to usual tx ■ Coma, seizures or altered behavior or persistent hypoglycemia caused by a sulfonylurea ○ Persistent hyperglycemia not responding to tx w/ metabolic deterioration ○ Recurrent fasting hyperglycemia > 300 or a1c level more than 2xs upper limit refractory to outpt tx Hyperglycemic Crises - AH! Emergency!! ● Diabetic Ketoacidosis (DKA) ○ Hyperglycemic state w/ Ketones ← Hallmark sign!! ■ Sugars 250-300 range ■ Lot of Ketones in urine ■ Osmolality less of an issue ○ Acidosis → Anion gap ■ pH < 7.3 ■ Bicarb - HCO3 < 15 ○ Seen more in T1DM ■ Juvenile, kids ○ Presentation ■ Abd pain, N/V, Kussmaul respirations, dehydration ■ Fruity odor to the breath, tachycardia, hypotension, changes in consciousness ○ Testing for Ketones ■ Test when BS > 250 ■ Illness, infection, fever and/or stress ■ If positive → drink water, take correction insulin, avoid exercise, monitor, call provider ○ Management ■ Fluid resuscitation, IV insulin, electrolyte monitoring & replacement & investigate & treat underlying illness or infection ● Hyperglycemic Hyperosmolar Syndrome (HHS) ○ Hyperglycemic state w/ hyperosmolality ■ Sugars > 600 ■ Blood is like motor oil w/ so much sugar → osmolarity increases ■ pH > 7.3 ■ HCO3 > 15 ○ AMS due to Dehydration

■ Can lead to brain swelling, coma, death :O ■ Seizures, tremors, hemiparesis & disorientation ○ Can be caused by illness, infection, burns, meds, new dx of dm, dehydration ○ Seen in T2DM ● What to do as a provider ○ Recognize s/s & differences ■ Pt w/ AMS, diabetic ○ Check their blood sugar!! ■ If it’s 250+ → ER! ● Ya sick . Maybe you got COVID, maybe its the flu but either way lets taco bout it ○ Rising BS may be first sign ■ Monitor Q4 Hours ■ BS > 200 → check for ketones ■ Give supplemental insulin Q 2-4 hours ○ Stay hydrated! ■ Provide antiemetics if unable to tolerate fluids ○ Take DM meds even if you are not eating!!! ■ Most common cause of DKA is omission of insulin when sick ○ Contact provider if: ■ Difficulty breathing ■ Vomiting persisting > 6 hours ■ Elevated BS > 300 unresponsive to insulin after 2 doses ■ Moderate or large ketos > 0.6 Hypoglycemia - Cold & Clammy need some candy! Renal Disorders Across the Lifespan Lab review! What are we casting out ● RBC casts → Suggest underlying proliferative glomerulonephritis (GN) ○ The blood is renal in origin! ○ Implies RBCs extrude into renal tubules from inflamed interstitium ○ Limited sensitivity. No casts? Does not r/o GN! Casts? Not exclusively mean GN ● WBC casts → Suggest interstitial or less likely glomerular inflammation ○ Clinical suspicion for acute interstitial nephritis BUT absence of WBC casts does not rule it out! ● Renal tubular epithelial cell casts → Any desquamation of tubular epithelium ○ Includes Acute tubular necrosis (ATN), acute interstitial nephritis & proliferative glomerulonephritis ● Granular casts → Degenerated cellular casts or aggregation of proteins w/in cast matrix ○ May be coarse or fine in nature ■ Coarse deeply pigmented granular casts ex. “Muddy brown” or heme-granular casts → think ATN ● ATN = leading cause of AKI in hospital pts ○ Pts w/ ischemic or toxic injury to the tubular epithelial cells, cell sloughing into the tubular lumen, due to cell death or to defective cell-to-cell or cell to basement membrane adhesion

■ May lead to formation of granular &/or epithelial cell casts ● Hyaline casts ○ Slightly more refractile than water, transparent, empty appearance ○ Seen w/ small volumes of concentrated urine or w/ diuretic therapy ● Waxy casts ○ Last stage in degen of granular cast, homogeneous in appearance & have sharp indentations & darker distinct edges ○ Nonspecific, observed in variety of acute & CKD ● Broad Casts ○ Wider than other casts, due to formation in large dilated tubules w/ little flow ○ Assoc w/ advanced CKD Hematuria? Hema what? Hema gonna give you an overview ● It’s blood in the urine! Can be visualized or occult (ya can’t see it) ○ 3+ RBCs per High-power microscope field (HPF) ○ Transient = 1 occasion ○ Persistent = 2 or more consecutive occasions ● What could be causing it? Diffs! UTI, Malignancy! Nephropathies! Ya period! ○ Drugs, diet, exercise, menses ■ Drugs: Beta-lactam atbx, sulfonamides, NSAIDs, Rifampin, Cipro, Zyloprim, Tagamet, Dilantin, anticoags ■ Bladder irritants: Caffeine, spices, chocolate, alcohol, citrus fruits, soy sauce (this is essentially my diet, am I screwed?) ■ *Hematuria is the most common sign of bladder ca* ○ Based according to anatomical site of the blood source ■ Isolated: Bleeding anywhere from renal pelvis to urethra ■ RBC casts: Injury to nephron ■ Gross: Acute cystitis, urethritis ■ Proteinuria & hematuria : Glomerular or interstitial nephritis ■ Colicky, flank pain: Ureteral stones ● Clinical Presentation ○ Hx→ strenuous exercise, strep infection/URI, nephrolithiasis, family hx (esp renal & DM) & recent travel ○ Physical ■ CVA tenderness → think Pyelo! ■ Abd mass → neoplasm or polycystic kidney dz ■ Suprapubic tenderness → bladder etiology ■ Urethral discharge → urethritis ■ Check that prostate (get those fingas ready) Enlarged &/or tender prostate → BPH or prostatitis ■ Check that pelvis in women (sorry ladies) ■ Hemoptysis & acute renal failure → Goodpasture syndrome ○ Glomerular hematuria assoc w/ significant proteinuria, erythrocyte casts & dysmorphic RBCs! ■ Berger dz, Alport syndrome & thin basement membrane dz are common causes of glomerular hematuria ○ Dx ■ Catheterized urine specimen ● Prob gonna have to cath kids ■ UA & Urinary sediment analysis ■ Intravenous urography (IVU) ■ US - ped or preggo pts ■ CT scan - kidney stones! NO CONTRAST ■ Cystoscopy ● Management ○ ID & Dx problem. Depends what is causing it ○ Urological referral ■ Depending on what’s going on could result in surgery! Hematuria in Kids ● Gross - Visible blood ○ Red or pink ■ More bright red think lower UT issue ○ Brown or tea colored ■ Think higher UT issue as blood can oxidize in the bladder ● Microscopic - Not visible w/o a microscope ○ Appears normal ○ More than 5 RBC per high power field (HPF)

● Dipstick ← 1st thing you do! ○ For heme- + when detects 1-2 RBC per HPF ■ + for heme but no increased # of RBC? Test for myoglobinuria & hemoglobinuria ○ Confirm w/ microscopy ■ Possible for false positive or negative w/ dipstick ○ False positives ■ Contaminated w/ cleansing agent used to clean perineum ■ If the urine is more alkaline ex. pH > 9 ○ False negatives ■ If urine is too dilute ■ If urine is highly acidic pH < 5 ○ Hematuria mimics ■ Menstrual blood ■ Certain foods or drinks ex. Beets, food dyes ● Even Senna ■ Always ask what the pt is eating, meds they take ● Ex. Pyridium, rifampin or nitrofurantoin ● Gross Hematuria ○ Hx: Timing, fever, urinary s/s, flank pain ■ Is it occuring after exercise? ■ Transient or more persistent? ■ Is there blood @ the beginning of the urine stream? ● More consistent w/ something @ the end of the urinary tract like from the urethra ■ Is the blood more late midstream or late stream ● More likely originates higher up in the GU tract ■ Any clots in the urine? ● More suggestive of a extraglomerular disease ■ Trauma, Recent URI symptoms ● URI or sore throat can trigger glomerulonephritis ● IgA nephropathy can be preceded by viral URI ■ Fever? ● More suggestive of infection ex. UTI ● Flank pain too? Pyelonephritis or renal stones ■ Hx of abuse ● Trauma to the kidney can cause gross hematuria ● Microscopic Hematuria ○ Hx: family hx, fever ■ Fam hx of renal problems? ● Any hx of deafness- assoc w/ Alport syndrome which is a thin basement membrane dz ● Polycystic kidney disease ■ Urinary symptoms, infection symptoms ■ Rash, joint pain, sickle cell trait ● Rash w/ joint pain think possible autoimmune process ○ Ex. Lupus nephritis or Henoch-Schonlein purpura nephritis ● Sickle cell trait can cause nephropathy ○ Usually an isolated event ■ Repeat UA another 2 times to determine ■ If persistent could be transient related to exercise ● Exam ○ Bp, temp, wt & growth, assess for edema ■ Kids w/ renal dz like nephrotic syndrome can have growth failure and wt loss ○ Lungs, joints, skin for rashes ■ Check for signs of fluid overload ● Pulmonary edema ● Edema in the extremities or in the face ■ Joints & skin for autoimmune process ○ CVA tenderness, urethral meatus *This should be Chaperoned!* ■ Checks for evidence of irritation or some sort of trauma in the area that is causing urine to have blood toned appearance ● Initial Workup

○ Non-glomerular ■ UC, urine calcium to creatinine ratio ● Looking for infection or renal stones ■ Causes: Tumors, calculi & infections ○ Glomerular ■ BMP, CBC, Albumin ■ Urine protein to creatinine ratio ■ Complement C3 and C4 ● Elevated in post-strep glomerulonephritis ■ Throat culture & antistreptolysin O (ASO) ● Looking for post strep glomerulonephritis ■ If autoimmune suspected ● Antinuclear antibody (ANA) ● Anti-double-stranded DNA (anti-dsDNA) ○ UA & Dipstick results: ■ UA and dipstick negative? ● Think of foods/meds that could cause urine to be discolored ■ UA + for heme but no RBC? → possibly myoglobinuria or hemoglobinuria ■ UA + for RBC & -/+ for heme? Look @ microscopy and morphology of RBCs that are visible ● Abnormal morphology think glomerular cause! ● RBC casts also think glomerular! ● Diff Dx ○ Young children ■ Hypercalciuria ■ Nephrolithiasis ■ Postinfectious glomerulonephritis (GN) ■ UTI ■ Less common ● Alport syndrome ● Vasculitis ● Wilms tumor ○ Assoc w/ several congenital anomalies ex. Cryptorchidism, von WIllebrand dz, ureteral duplication, hypospadias ○ Large abd mass, unilateral ● Rhabdomyosarcoma ○ Gross hematuria & voiding dysfunction ● Sickle cell ○ Can cause gross but not always ● Henoch-Schonlein purpura (HSP) ○ Gross hematuria, abd pain w/ow/o bloody stools, joint pain, purpuric rash ○ Older kids/adolescents ■ Exercise induced ■ Hypercalciuria ■ Immunoglobulin A (IgA) nephropathy ■ Sickle cell ■ Trauma ■ Thin basement membrane disease ■ Less common ● SLE, interstitial nephritis, GN, drugs of abuse, Alport syndrome ● Refer ○ ER for gross hematuria post trauma ○ Ped nephrology ■ HTN w/ hematuria ■ Proteinuria, Renal dysfunction ■ Dysmorphic RBCs or urinary casts ■ Structural pathology ■ Renal cysts ■ F/U nephrolithiasis Hematuria in Adults

● Most Common Etiologies ○ Hematuria- > 3 RBCs per high power field in a urine sample ■ Exclude other causes of blood in the urine like menses or vigorous exercise ■ If + dipstick but - for RBC, repeat a few times ■ Persistent Hematuria = 2 or more consecutive occasions ○ Most common etiology of gross and microscopic is UTI ○ Gross hematuria - 10-40% have malignancy ■ UTI ● Urethritis ■ Urological cancer ● Bladder most common ● Gross hematuria is the initial symptom in 80% of bladder cas and 50% of renal ca ○ Significant risk of malignancy in older men ○ Smoking is a major risk factor! ● Risk for malignancy is increased in men, over > 35 yo and anyone w/ hx of smoking ■ BPH ● Cause of gross hematuria in prostate ca ■ Urolithiasis ■ Glomerular disease ● Lupus nephritis or glomerulonephritis ■ Renal mass ■ Polyps, strictures ○ MIcroscopic hematuria ■ UTI, ← most common cause ■ BPH, Urinary calculi ● Hx ○ Exercise ○ Sexual activity ○ Menstruation ○ UTI symptoms, pain ○ Meds & food ○ Recent hx of infection ○ Family hx, smoking ■ Ex. polycystic kidney dz ○ Work-related exposures, travel history ■ Exposure to chemicals and dyes like benzenes ○ Exposure to TB or schistosomiasis ● Work Up ○ Comprehensive physical exam ■ BP, CVA tenderness ■ Genital exam ● R/O genital causes of bleeding ex. Menses ○ Gross ■ Urine cytology ■ Urine microscopy & culture ■ Cystoscopy ■ Imaging of upper UT ● CT urography is the procedure of choice ○ 94-97% sensitive for detecting any abnormalities ■ CBC, renal function tests ■ PSA ■ Clotting screen if @ risk ■ Urine hCG ○ Micro ■ Microscopic exam of urine ■ Renal function tests ■ Cystoscopy ● All pts > 35 yo or younger if clinically indicated ■ Imaging of upper urinary tract ● Management

○ Refer to nephrology if glomerular disease suspected ■ Protein in urine, RBC casts, renal dysfunction, dysmorphic RBC, elevated creatinine ○ Microscopic hematuria ■ Repeat UA after benign etiology or UTI prescription ● Repeat after UTI treatment ■ If w/u negative, repeat UA yearly ■ Repeat w/u after 3-5 mo if persists ○ Gross hematuria ■ Urology referral for all pts if cause not found ■ Monitor closely if w/u negative ● CT to look for mass ● Cystoscopy if CT nondiagnostic ● Cystoscopy nondiagnostic? Urology may request renal biopsy Myoglobinuria 1 ● Myoglobin in the urine assoc w/ acute tissue damage or rhabdomyolysis. Why is it bad? ● Myoglobin is released into the bloodstream with muscle damage. Myoglobin breaks down into byproducts that are harmful to the kidneys, resulting in acute renal injury ● As long as renal injury is prevented and rhabdomyolysis does not occur, myoglobinuria is not associated with long-term effects or high mortality ● Myoglobinuria generally clears or improves in 10 to 14 days Dipstick positive for heme? ● Dipstick positive for heme but no increased numbers of RBCs are seen on microscopic examination? ● The urine should be tested for myoglobinuria and hemoglobinuria→ Get a UA ● Myoglobinuria is often confused w/ hematuria as it is associated w/ a red- or rust-colored pigment in the urine & causes a positive blood test on a urine dipstick. Proteinuria: What is it? ● Hallmark of renal dz ○ Most often glomerular in origin ○ Overproduction of filterable plasma proteins ○ Microalbuminuria = excretion of 30-150 mg/per day → sign of early renal dz!!! ■ Especially in pts w/ DM! ○ Macroalbuminuria = > 300mg/day ● Urinary protein excretion of > 150mg/day (10-20 mg/dL) ← dis bad bad ○ Can be acute or chronic ○ Common finding in primary care ■ The amount matters! How much proteinuria? ○ May be correlated w/ complex illness ■ Can be functional: acute illness, emotional stress, excessive exercise, benign process ○ Intermittent proteinuria: Asymptomatic, discovered w/ urine dipstick ■ Don’t worry about as much, usually in regular physical or UTI ○ Transient = temporary change in glomerular hemodynamics ■ Benign or self limited, can be due to exercise, fever, CHF ○ Persistent = 1+ proteinuria on dipstick 2 or more times in 3 mo ■ Pathologic!!! ■ Must investigate! ■ Diabetic? Usually result of DM nephropathy ● Most accurate way to quantify protein in urine is via 24 hour urine collection ○ Ask how they collect their pee, is it in the fridge? Clinical Presentation of Proteinuria ● May vary from pt w/ functional proteinuria due to exercise compared to advanced diabetic w/ nephrotic syndrome ● ****Any value of 1+ or > on 2 or more occasions should be investigated!!!!***** ● Screen preggo women! Get a UA!!! ○ Proteinuria before 24 wks gestation indicates likely glomerulonephritis

■ After 24 wks usually a sign of preeclampsia ● Check her BP!!!! ○ Look for Asymptomatic UTI ● Obtain complete & thorough person & family hx especially regarding DM & renal dz ○ Ask about acute & chronic illnesses, surgery, dx procedures (esp those requiring contrast media), urinary frequency or symptoms suggesting infection, risk factors, HIV infection. Recent physical activity esp exercise or cold weather activities ■ Have you been stressed? Sick? ■ CHF and seizures can cause transient proteinuria ○ Meds prescription & OTC ex NSAIDs ● Dx ○ 1st step → Dipstick! UA, C&S (takes a few days) ■ Dipsticks can have issues ex. Contaminated, how long you wait, interpretation ○ CMP (includes kidney and LFT) ○ CBC w/ diff → infection! Lipid profile → CV risk factors ■ Remember diff gives types of WBCs! Can help distinguish viral vs bacterial ○ Fasting blood sugar, A1C → checking for DM ■ If you do not suspect DM do not order!!!! ○ 24 hr urinary protein excretion or spot urinary protein/creatinine ratio → tells amount! ■ 3-3.5 g/day protein excretion = Nephrotic syndrome → refer to nephro!! ● Nephrotic syndrome usually accompanied by hypoalbuminemia, HLD & edema ■ > 150mg in 24 hours = glomerular kidney dz ● Glomerular kidney disease is usually assoc w/ > 1g woh ○ MIcro → sediment, casts, etc ○ Bence Jones proteins ■ If present get serum protein electrophoresis & refer for further eval to r/o multiple myeloma ● Diff Dx ○ Glomerulonephritis ○ Hepatitis induced vasculitis ■ If they have those risk factors ○ Urate-related renal dz ○ Diabetes ○ Other systemic dz or structural abnormalities ● Management ○ Depends on the underlying cause! ■ Gotta treat underlying dz ■ Eliminate known trigger meds, no more poppin ibuprofen ■ Na & Protein restricted diets ● No cheesesteaks D’: ● Eat some broccoli! ○ ACEI reduce proteinuria by decreasing intraglomerular pressure = decreased proteinuria ■ ARBs also reduce proteinuria ○ HLD &/or HTN? End target organ damage! :O Aggressive treatment ○ CHRONIC RENAL FAILURE? → AGGRESSIVELY TREAT THEM FOLKS ○ Goal = Protein excretion rates (as measured by collection of a 24 hr urine) of < 1g/day! ■ Higher rates increase CVD Proteinuria in kids ● Overview ○ Present 10% of urine testing in school-age children ■ Prevalence increases in adolescence and is more common in girls ○ Benign vs pathologic ■ Most of the time is benign ■ Can be a marker that something serious is going on if in conjunction w/ hematuria ○ Transient vs persistent ■ Transient → temporary ● May occur w/ fever ● After exercise, stress or exposure to cold ● Resolves when inciting factor is removed ■ Persistent

● Constant ● More suggestive of pathologic cause ○ Categorized as either glomerular or tubular ■ Glomerular ● Increased filtration of protein across the glomeruli ● Being excreted in the urine ■ Tubular ● Increased excretion of proteins in the tubules ■ Secretory ■ Overflow proteinuria ● Office testing ○ 99% sensitivity & specificity ■ Detects albumin. No other type of protein ■ Trace amount = 15 mg/dL ○ 1+ (30mg/dL) or more is abnormal ○ False positive ■ Alkaline urine, pH > 8 ■ Concentrated urine, higher specific gravity ○ False negative ○ Sulfosalicylic acid test ■ Detects all forms of proteinuria ■ Generally used as a supplementary test when you’re thinking other proteins are involved that may not be detected on urine dipstick or UA ● Orthostatic Proteinuria ○ Most common in adolescent males ■ Benign, no clinical significance ○ Increased protein excretion after the pt has been in the upright position for 4-6 hours ■ No protein excretion supine position ■ No protein excretion in the morning ○ Trace protein? Repeat dipstick in AM ■ Get 3 early AM voids to check for protein ○ 1+ or more protein: urine protein to creatinine ratio & UA in AM ■ If + and abnormal findings → refer to nephro ■ If - urine protein to creatinine ratio → stop investigation, repeat urine in 1 yr ● Transient Proteinuria ○ Fever, seizure ○ Exercise, stress, dehydration ○ Cold exposure, idiopathic ● Persistent proteinuria ○ Evaluation ■ Full H&P ■ Bun & creatinine ■ Electrolytes ■ Urine microscopy ■ Complement ■ ASO ■ ANA ■ Anti-DNA ■ Hep B, Hep C ■ HIV ○ Diff dx ■ Glomerular ● Alport, HSP, SLE, nephrotic syndrome, DM, IgA nephropathy ■ Tubulointerstitial ● Pyelonephritis, polycystic kidney disease, renal tubular acidosis, toxins, meds Nephrotic Syndrome ● Overview ○ Adult incidence 3 per 100,000 people ■ Most cases idiopathic ■ Diabetes is the leading cause of nephrotic syndrome (75% of cases)

○ Children incidence 2-7 per 100,00 people ■ Kids < 16 yo ● Definition - Large amount of protein being spilled in the urine ○ Nephrotic range proteinuria ■ 3.5g/day or > in adults ■ > 40 mg/m2/hr in kids ■ A 1st morning urine protein/creatinine ratio of 2-3 mg or more ○ Edema ○ Hypoalbuminemia ○ Hyperlipidemia ● Etiology ○ Kids ■ Primary - Idiopathic - Not curable ● Thought to be due to an immunological response ● Minimal change dz ○ 80% of cases ● Focal segmental glomerulosclerosis (FSGS) ● Membranoproliferative glomerulonephritis (MPGN) ■ Secondary ● Lupus ● HSP ○ Adults ■ Primary - 80-90% of cases ● FSGS ● Membranous nephropathy ● Minimal change dz ■ Secondary ● DM, lupus ● Amyloidosis ● Infections ○ Patho ■ Glomerular basement membrane & endothelial surface layer damaged ● Basically there’s damage to glomeruli → protein permeating barrier → large amount of protein secreted in urine ● S/s ○ Edema ■ Swelling in lower extremities or periorbital edema ■ Can be insidious in onset ■ Can be dependent ● May wake up w/ edema and then as the day goes on it gets better ■ As dz progresses → more generalized edema ○ Foamy urine ○ Wt gain, fatigue ○ Anorexia ○ In kids if severe ■ Abd pain ■ Resp distress if pulmonary edema ● Pediatric exam ○ Periorbital edema, lower extremity edema ■ Possibly edema in genital area ex. Labia or scrotum ○ Look for evidence of systemic lupus or HSP ■ Skin for rashes ○ Lung exam ■ Assess for edema ○ BP for hypo or hypertension ■ Most pts have either normal BP or hypotension ● Adult exam ○ Pedal & ankle edema, lower extremity ■ Usually adults do not have periorbital edema unless its more advanced. ○ Transverse leukonychia on fingernails

■ Not specific to nephrotic syndrome ○ Xanthomas - fatty deposits on the skin ■ Occurs from having very high levels of cholesterol in the body ● Dx ○ All of the following: ■ Nephrotic range proteinuria ■ Peripheral edema on exam ■ Low serum albumin ○ Hyperlipidemia often present ○ Additional testing to assess for complication & ID underlying cause ■ Check renal function, CBC, UA w/ microscopy ■ Serum albumin, electrolytes, glucose, lipids ■ Order additional testing if you think it may be caused by lupus ● Management ○ Kids ■ Refer to nephrology! ■ Oral steroids for 2.5-3mo ● KIDGO recommends 5 mo, depends on guidelines ● Nephro will determine ■ Management of edema ● FR, Sodium restriction, diuretics ■ Steroid-resistant--renal biopsy ■ Diet ● Assure adequate nutrition for kids for growth and development ■ Calcium & vit D ■ BP ○ Adults ■ Refer to nephrology!! ■ ACE inhibitor ■ Manage edema ● Diuretics ■ Diet ■ Statin for hyperlipidemia ■ Immunosuppressive tx depending on cause ■ Prophylactic anticoagulant if @ high risk ● 25% chance of developing thrombosis Berger Disease - IgA Nephropathy (No you don’t get it from eating too many burgers) ● Definition - deposition of IgA immune complexes in the cells of the glomeruli ○ Most common cause of chronic glomerulonephritis ● Cause ○ Who’s to say? Maybe idiopathic ○ Possibly some sort of genetic susceptibility to the dz ○ Often preceded by viral illness ex. URI ○ Can be due to liver dz, GI infections, autoimmune dz, other viral illnesses ● S/S ○ Asymptomatic microscopic hematuria ■ As dz progresses may develop gross hematuria ○ Dz progression: ■ Proteinuria, HTN ● Proteinuria not in range of nephrotic proteinuria ■ Elevation of Glomerular filtration rate (GFR) ■ 40% can develop ESRD after approx. 20 yrs ○ RBC casts on UA ● Dx ○ Renal biopsy for definitive dx ■ May be deferred for some pts who just have a mild IgA nephropathy ● Ex. mild proteinuria, hematuria and normal BP ● Monitor closely ● Management

○ Refer to nephro ○ Manage along w/ nephro ■ Monitor UA, BP ● Can treat w/ ACE inhibitor or ARB ○ Goal: < 130/80 ● Watch their proteinuria ○ If dz is progressing and not responding well to ACE → immunosuppress that ish w/ corticosteroids or other meds if proteinuria continues Acute Glomerulonephritis (GN) ● Glomerulonephritis - 10-15% of glomerular dz ○ Proteinuria, Hematuria & RBC casts in the urine ■ 60% have gross hematuria ● Clinical presentation ○ Often accompanied by HTN, edema, azotemia, decreased urination ○ Renal salt and water retention in the body ● Cause ○ Nature of glomerular insult unknown ■ Believed to be caused by circulating immune complexes in the glomerular tufts ■ Cellular immunity involved ■ Diseased capillary & glomerulus lets protein and RBC casts into the urine ○ Infection most common ■ Most commonly streptococcus & staphylococcus ● Group A strep ○ Starts 1 - 4 wks after infection ■ Other infections ● Gram - bacteria, virus, parasites, fungal infection ■ Post Strep GN is most common in kids. Others: ● Focal segmental glomerulosclerosis ● Membranoproliferative glomerulonephritis ● Immunoglobulin A (IgA) nephropathy ■ Staph Gn most common in elderly ○ Non infectious causes ■ HSP, SLE, vasculitis ○ Primary renal disease ■ IgA, MPGN ● S/S ○ Gross hematuria ○ Proteinuria ■ Small amount, not in nephrotic range ○ Edema , lethargy ■ “Look like a wet noodle” lol ○ Fever, wt gain, elevated BP ■ Wt gain may appear in the abd ○ May have a rash w/ post strep ● Workup ○ Postinfectious GN ■ UA & Culture w/ microscopy ■ Throat culture ASO or anti-DnaseB titers ● R/o post strep ● ASO rises about a week after infection , remains elevated for several months ■ Serum complement levels ( C3 , C4) ● Decreased in post-infectious glomerulonephritis ● Resolves by 8 weeks ■ Inflammatory markers, renal function ■ CBC w/ Diff ● Inflammatory markers ex. Sed Rate, ESR ● Look for left shift ■ Creatinine ○ Other causes

■ ANA ● If sus Lupus ■ Antibody to glomerular basement membrane (anti-GBM) ● Management ○ Same day nephrology referral or ER ■ Elevated BP, Edema, dyspnea → HOSPITAL bye bye ○ Acute process lasts up to 2 weeks ○ Antibiotics ■ Do not reverse GN ■ Give in post-strep to resolve strep infection & prevent spreading of nephritogenic streptococci to contacts ■ Tx w/ penicillin if not contraindicated ○ Focus on treating HTN & edema ■ Loop diuretics ■ Salt restriction ○ Kids w/ persistent HTN ■ Start on vasodilator ○ Corticosteroid if severe ○ Hematuria may persist for 6 mo - 1 yr after resolution of acute GN ○ Proteinuria may persist for months ■ Still proteinuria after a year → nephro refer ○ Complement should resolve in 8 weeks ■ If still low → nephro refer ○ Renal function ■ Track after nephritis has resolved for 4-8 wks ● Nephritic vs Nephrotic syndrome ○ Nephritic ■ Hematuria - gross ■ Small proteinuria ■ Edema, HTN, oliguria ○ Nephrotic ■ Nephrotic range proteinuria, hypoalbuminemia ● MASSIVE protein loss assoc w/ adema

■ Hyperlipidemia Chronic Kidney Disease (CKD) ● Overview ○ 1 in 7 people in the US have CKD ■ 15% of adults, 37 mill people ■ Most common cause - DM, HTN ● Next is glomerular dz - 7%, Polycystic kidney 1.6% ○ Often doesn’t produce any symptoms early on ■ It’s yo job to screen for early signs! ● Catch it early to prevent progression! ● Look for marks of kidney damage ○ GFR decreased, increased serum creatinine, albuminuria/proteinuria in urine ○ Abnormalities of kidney structure or function for more than 3 mo w/ implications for health w/ either ■ One or more markers of kidney damage ■ GFR < 60ml/min/1.73 m2 for 3mo or more ○ Risk Factors ■ Dm, HTN, heart problems or stroke, obesity ■ Family hx, tobacco use, > 60 yo ■ Polycystic kidney dz, tubular interstitial dz ■ Prolonged use of nephrotoxic drugs ex. NSAIDs, herbal supplements ○ Diabetes and CKD ■ High glucose levels build up on the glomeruli → scarring on glomeruli → not able to function properly → not able to filter blood properly → they fucked ● Staging of CKD ■ **Note that a decline in GFR alone is not diagnostic of CKD w/o the presence of other markers, particularly in oldies** ○ Stage 1 GFR > 90 w/ some evidence of kidney disease ■ Ex proteinuria, hematuria, structural abnormalities, microalbuminuria ○ Stage 2 GFR 60-89 w/ evidence of kidney disease ○ Stage 3 ■ 3A 45-59 ■ 3B 30-44 ■ *note in stage 3 need to decrease dietary phosphate* ○ Stage 4 15-29 ○ Stage 5 < 15 = Kidney Failure RIP ma kids ● S/S ○ Asymptomatic early on in dz ■ Again, catch it early!! ○ Concerning S/s that suggest acute renal problem ■ Sudden onset of listlessness, confusion, anorexia, N/V , edema & wt gain, HTN ■ Oliguria (UO < 400mL/day) or anuria (UO < 100mL/day) when assoc w/ elevated creatinine indicates a change in fluid volume status requiring dx testing ○ Advanced will develop symptoms: ■ GI ● N/V, Anorexia ■ Pruritus (Itchy skin) ● Due to uremia - high levels of urea in the blood ○ Uremia increases bleeding risk from impaired plt function ● Uremic frost ● Muscle cramps or twitching ■ SOB, sleeping difficulties ● Wake up @ night to urinate ■ Psychosocial ● Cognitive changes, Depression, fatigue, insomnia, suicide, sexual dysfunction ■ Peripheral neuropathy ■ CV: ● Atherosclerosis, Heart Failure, HTN, pulmonary edema, Pericarditis (heart rub sound) ● Pleural effusion (Pleuritic chest pain, pleuritic “rub”) ● May hear extra heart sounds

■ Hematologic ● Anemia, Leukopenia, Erythropoietin deficiency ● Screening ○ Annually if risk factors present ■ Kidney profile ● Spot urine for albumin to creatinine ratio (ACR) ○ Very sensitive for picking up very small amounts of protein ● Renal function, Serum creatinine to estimate GFR ■ UA ● Measure ACR! > 30? Get anotta one in the AM to confirm! ○ In pts w/ DM ■ @ the time of dx of DM2 ■ 5 years after type 1 dx ○ Serum cystatin C ■ Alternative to creatinine to estimate GFR & CKD ■ Beneficial when possible false positive suspected from the GFR ■ Not widely available, Pricey $$ so not commonly used ● Categorizing ○ By GFR & albuminuria ■ Determines and estimates progression of dz ■ Estimates morbidity & mortality ● Eval ○ Meds ■ Look for nephrotoxic ones & adjust ■ If they be poppin NSAIDS for pain they gotta stop ○ Diet hx ○ Assess for hypo and HTN on both arms & orthostatic BP ○ Peripheral pulse characteristics ○ Fundoscopic eval for: ■ AV nicking, diabetic retinopathy & papilledema ○ Abd exam ■ Auscultate for renal artery bruits, palpate the kids, inspect for distention that may be caused by ascites ○ Skin ■ Ecchymosis, rashes, uremic frost, pruritus ○ Serum lytes ■ Abnormalities occur in more advanced Renal Failure ○ Hgb A1C, Blood sugar ○ Lipid panel ○ Renal US if risk for structural dz ● Dx → creatinine, GFR, 1st morning or random UA to assess for albuminuria ○ Serum cystatin C-Based estimates of eGFR to confirm or exclude dx of kidney dz in pts w/ GFR < 60 ○ Urine sodium to dff between ATN & prerenal dz ● Management - Depends on the stage of dz! ○ BP control ■ Guidelines vary - most agree < 130/80 ● KDIGO, JNC, AHA/ACC ○ Meds ■ ACE inhibitor or ARB for diabetics w/ microalbuminuria w/ow/o HTN & pts w/ HTN ■ Low-dose ASA if controlled HTN & high risk for CVD ■ Statin in adults > 50 yo ● Reduces proteinuria & prevents GFR decline ○ Labs ■ Monitor for complications of CKD → elevated parathyroid hormone levels, serum lipids & decreased vit D levels, metabolic acidosis, hyperphosphatemia ○ HgbA1C target < 7% ○ Referral ■ Any pt w/ renal failure needs to be referred to nephro ■ Consider referral if pt has: ● Albumin to creatinine ratio > 300 mm , ● GFR < 30,

● Refractory HTN & on 4 HTN meds ● Pregressive decline ○ Decrease in GFR & 25% or greater drop in GFR from baseline ● RBC casts in urine > 20/HPF ○ **That we can’t explain** ● Abnormalities of potassium & albumin ● AKI or abrupt sustained decrease in GFR ● Hereditary kidney disease ● Recurrent or excessive stones ■ Comanage w/ nephro ○ Monitor depending on classification ■ Anemia ● Pts w/ chronic renal failure have anemia because erythropoietin is made in the kidneys ■ GFR & urine ACR ○ Monitor in advance stage ■ Acid base & electrolytes ■ Mineral & bone disorder ● Osteoporosis, osteopenia ○ Avoid unnecessary nephrotoxic drugs ■ Ex. NSAIDs ○ Vaccinations ■ Ex. PNA and Flu! ○ Diet & weight management ● To dialyse or not to dialyse ○ Dx of severe AKI to manage following conditions: ■ Metabolic acidosis w/ pH < 7.1 ■ Refractory hyperkalemia > 6.5 ■ Volume overload unresponsive to diuretic use ■ Uremic encephalopathy ■ Removal of toxic or drugs that can be removed w/ dialysis Acute Kidney Injury ● Causes ○ Any process that interferes w/ perfusion, filtration or excretion ○ Prerenal ■ Poor perfusion due to hypotensive shock ○ Intrarenal ■ Intrinsic abnormalities of vessels, glomeruli, tubules & interstitium ○ Post renal ■ Obstruction to the renal pelvis, ureters, bladder or urethra ● Hospitalization indications ○ Acute kidney injury (oliguria, anuria) assoc w/ elevated serum creatinine, acute fluid & electrolyte derangement

■ Nephrolithiasis - Kidney Stones ● Urinary Calculi → stones anywhere w/in the urinary tract (UT) ■ Nephrolithiasis → Kidneys ■ Urolithiasis → Urinary system ■ Ureterolithiasis → Ureters ■ MIgrate to the lower UT (bladder or urethra) ○ Stone formation occurs due to elevated levels of stone-forming salts & inadequate inhibitory proteins ○ Most common stones: ■ * Calcium Oxalate * ● Dietary one ■ Calcium Phosphate ■ Uric acid ● DM pts ■ Struvite stones ● Require early medical & surgical interventions ● Risk Factors ○ Reduced urinary flow & any factor reducing flow or volume!! ○ More common in men ■ Specifically Males between 40-70 yo ○ Females 50-60 yo ○ *Not common in kids* ■ If kid gets it there’s probably a fam hx of renal stones ○ Obesity, family hx ■ Sedentary lifestyle/occupation → drivers/desk workers ○ Hx of primary hyperparathyroidism, Gout, short bowel syndrome, hyperinsulinism, chronic metabolic acidosis, metabolic syndrome, CAD ○ Low fluid intake→ dehydration, diet related

■ Eating too many animal products, consuming high salt diet, oxalate, calcium ■ Tea, grapefruit/apple juice, cola, sports/energy drinks ■ Excess antacid use ■ Living in a warm climate→ cause you to sweat → dehydration ● S/S → vary based on size & location! ○ Renal colic - Intermittent severe pain usually felt in the flank ■ Can also be felt in the groin ■ If constant pain → think obstruction! ■ Starts low back, moves forward, descends into pelvis ■ CVA tenderness! ○ Increased urinary frequency, dysuria ○ If pain is severe → N/V, sweaty pale cool skin ○ Tachycardia, HTN ○ Could be asymptomatic ■ Detected on imaging study done for another reason ○ Hematuria ■ Micro or gross (more often gross) ○ Fever, chills ■ Sign of confined, non draining Upper UTI ● WIll need to be surgically removed ● Patho ○ Develop from microscopic crystals ■ Calcium or uric acid ○ Crystals adhere to the epithelium in the UT & form a stone ● Diff Dx ○ Other GU problems ○ GI problems ■ Appendicitis, PUD ■ Cholecystitis, Pancreatitis ○ In women - Gyno issues ■ Ectopic pregnancy!! ○ Dissecting AAA w/ risk factors ● H&P ○ Detailed family and person hx of stone formation, medical & med hx, occupation, dietary habits & fluid intake hx ○ Thorough abd exam ■ Include CVA tenderness! ● Work Up ○ UA, Culture & sensitivity to r/o infection, urinary pH (help diff type of stone) ■ Hematuria ○ Strain urine for stones and/or sediment ○ 24 hour urine collection ○ Only pt has fever → CBC w/ diff ■ Significantly elevated WBC raises concern of non draining UTI! ○ BMP ■ If calcium elevated → w/u for hyperparathyroidism and check PTH ■ Vitamin D ■ PTH ■ Creatinine may be elevated, microscopic hematuria common ○ KUB - fastest imaging study to ID renal stones that are radiopaque ○ Non-contrast CT *considered gold standard* ■ Can look for obstruction → renal enlargement, hydronephrosis, ureteral dilation, perinephric stranding & periureteral edema ○ US in pts w/ contraindications to CT ex. Preggo ■ Less sensitive ■ aid in dx & can be used as a screening tool for hydronephrosis, detecting the absence of expulsed urine (ureteral jets), & ID stones within the ureters, kidney, or renal pelvis. ● Tx → Pound fluids, Pain management, Flomax! ○ Majority of acute renal & urinary calculi can be managed conservatively through oral hydration, pain management & expectant stone passage

■ Depends on size, location of stone, presence/absence of infection, involving 1 or 2 kidneys, severity of symptoms ○ Uric acid stones ■ 1st line Potassium citrate to alkalinize the urine ○ Struvite stones ■ Antibiotics! If needed surgery! ○ No obstruction, non-complicated ■ Stone < 8 mm ● Stones < 5 are likely to pass ■ Increase fluids → > 2L/day, med expulsion tx ● Alpha blocker if BP can tolerate it to help pass stone early, dilate ureter ex Tamsulosin (Flomax) ○ Other option Ca channel blockers ex . Nifedipine ■ Control pain ● NSAIDS preferred 800 Ibuprofen or narcotics ■ Strain urine for 4-6 wks to see if stone passed & capture stone ● AUA recommends sending stone for analysis to see composition of stone ○ Conflicting guidelines whether or not to send stone ● If stone NOT passed w/in 4-6 weeks → refer!!! ○ Stone still there? ■ Refer for procedures Stone > 10 mm (10 per book, wolf said 8) ● Extracorporeal shock wave lithotripsy (ESWL), ureteroscopic stone removal (URS), percutaneous nephrolithotomy (PCNL) ○ Complicated stone ■ One of the following: ● Obstructed or Concurrent infection → consider hospitalization & refer to urology! ● Uncontrolled pain ● Preggo or stone > 5mm ■ Refer complicated stones! ○ Asymptomatic stone? ■ Monitor over 1-2 years in primary care by doing a US ○ Complications ■ UTI w/ potential for progression to pyelo, sepsis, CKD ■ Hydronephrosis ● Education ○ Educate pt on how they can prevent stones bc they tend to recur ■ 40% risk of recurrence in 5 yrs ○ Lifestyle changes ■ If overweight, obese → Lose weight!! ■ Consume low animal protein diet, hydrated, low salt diet ○ If recurrent stones ■ Targeted tx specific to what the stone is - calcium or uric acid