Renal Pathophys Flashcards

Question

Answer 1

* Most common type of AKI (70% of community-acquired cases) Caused by decreased renal perfusion * Reduced circulating volume (GI losses, blood loss, diuretic use, osmotic diuresis – DKA, insensible loss – burns) * Reduced cardiac output (heart failure) * Systemic vasodilation (septic shock) * Medications * ACE inhibitors, ARBs, NSAIDs * Obstruction of the renal artery (thrombosis/embolus, stenosis, or aneurysm)

Answer 2

NSAIDs * Vasodilation of the afferent arterioles mediated by prostaglandins * NSAIDs block the production of prostaglandins → vasoconstriction and possible AKI ACE/ARB * Vasoconstriction of the efferent arterioles mediated by angiotensin II * ACEi/ARBs block the effects of angiotensin II (vasoconstriction) → vasodilation of the efferent arterioles (renal protective) * In patients with renal artery stenosis, the introduction of an ACEi/ARBs can lead to a drop in glomerular filtration pressure

Answer 3

* Caused by direct damage to the glomeruli and/or tubulointerstitial structures Acute tubular necrosis (ATN) * Damage to the tubular cells * Caused by a lack of blood flow to the kidneys and nephrotoxic agents Acute interstitial nephritis * Inflammatory cell infiltration into the kidney interstitium * Caused by medications, infections, or autoimmune diseases Vascular disease * Atherosclerosis and vasculitis Glomerular disease * Glomerulonephritis (presents with hematuria) * nephrotic syndrome (presents with proteinuria)

Answer 4

* aminoglycosides * vancomycin * cisplatin * heavy metals (lead, mercury) * ethylene glycol (anti-freeze) * radiocontrast * lithium

Answer 5

* Caused by inadequate drainage of urine distal to the kidneys (obstruction) leading to back pressure on the kidneys and hydronephrosis * May occur at any point in its course from the renal pelvis to the urethra Causes of obstruction * Urinary calculi * Benign prostatic hyperplasia (BPH) or prostate cancer * Bladder outlet obstruction * Urethral stricture * Gynecologic tumors (ovarian cancer, uterine fibroids, cervical cancer)

Answer 6

Hyperkalemia * Due to decreased renal excretion of potassium * Increases the probability of cardiac arrhythmias Hyperphosphatemia * Due to decreased renal excretion of phosphate Metabolic acidosis * Inability of the kidneys to excrete acids * Exacerbates hyperkalemia * Increases the probability of cardiac arrhythmias

Answer 7

Traumatic (msk compression) * Crush injuries * Victims of prolonged restraint, torture, or physical abuse * Surgical procedure with prolonged muscle compression * Acute lower-limb compartment syndrome * High-voltage electrical injury Non-Traumatic, Exertional * marked physical exertion when 1+ risk factors is present: sickle cell trait, physically untrained, hot/humid conditions, impaired heat loss (ex: anti-cholinergic meds, heavy football equiment) * pathologic hyperkinetic states: grand mal seizures, delirium tremens (severe type of EtOH withdrawal), psychotic agitation, amphetamine OD Non-Traumatic, Non-Exertional * Prolonged immobilization * Alcohol use * Drug use: Illicit (heroin, cocaine, LSD, methadone) or Prescription (statins, colchicine, daptomycin) * Toxins: Snake venom, mushroom poisoning, carbon monoxide * Infections: Viral (influenza A & B, coxsackievirus) * Inflammatory myopathies (dermatomyositis) * Electrolyte abnormalities: Hypokalemia or Hypophosphatemia

Answer 8

* Muscle injury * Influx of extracellular sodium and calcium into the myocytes; water follows sodium distorting the integrity of the intracellular space * ↑ intracellular calcium causes a sustained myofibril contraction → ATP depletion within these cells * Activation of lipases and proteases → damage of the myocyte cellular membrane * Release of intracellular components (creatine kinase (CK), myoglobin, potassium, phosphate) that enter the bloodstream * Myoglobinuria and electrolyte abnormalities cause end-organ complications (AKI most common systemic complication)

Answer 9

**Intracellular fluid** * Potassium (K⁺) – main cation * Magnesium (Mg2⁺) * Proteins * Phosphates (HPO₄²-/H₂PO₄-) – main anion * Electrically balance the intracellular cations along with the negatively charged proteins * MP3 (Mg, potassium, protein, phosphate) Inside **Extracellular fluid** * Sodium (Na⁺) – main cation * Controls ECF volume and water distribution in the body – water follows sodium * Calcium (Ca²⁺) * Chloride (Cl-) and Bicarbonate (HCO₃-): Chloride is the most abundant anion in the ECF * Anions balance the extracellular cations

Answer 10

* renal fusion when a portion of one kidney is fused to the other due to abnormal migration of kidneys; horseshoe most commonly is each pole fused together * isthmus lies in the mid-line or sometimes slightly lateral to the mid-line and can be composed of renal parenchyma or just fibrous tissue, but the renal collecting systems remain separate Anatomy * fusion occurs before the kidneys ascend from the pelvis to their normal dorsolumbar position (5th-9th wks gestation) * fusion abnormalities found in lower lumbar vertebral level (L4/5) * blood supply variable

Answer 11

* 5% cancers in children under age 15 * second most common abd tumor * some occur in setting of associated malformations or syndromes * bilateral tumors more common in younger kids * males dx earlier than females * occurs most commonly between ages 2-5

Answer 12

* Exam should be focused on whether testes can be palpated in the scrotum or inguinal canal, appearance of the genitalia, and any midline defects. * Will need two hands to perform the exam. * One hand milks the testes from the deep inguinal ring to the scrotum. * The second hand lies over the scrotum to hold the testis. * If the testis retracts back to the inguinal canal, it is likely undescended testicle. If the testis stays in the scrotal sack, then likely it will be a normal testicle. * Squatting position for older children or in a warm bath is helpful for examination.

Answer 13

* Cystoscopy is performed in the OR with local anesthesia or in the office with lidocaine injected into the urethra to look for a bladder tumor. * If a bladder tumor is noted, then patient is scheduled back in the OR with either general or regional anesthesia for transurethral resection of the bladder tumor (TURBT)

Answer 14

* Intravesical therapy is using chemotherapy or immunotherapy that is delivered directly into the bladder by a urethral catheter to help reduce reoccurrence after a complete transurethral resection. * Agents are given weekly for 6-12 weeks. * Recommend to patients they keep the liquid in their bladder for 2 hours if possible. * Can be given in the urologist’s office. * Most effective agent to reduce disease progression is bacillus Calmette-Guerin (BCG). * Side effects include irritative voiding symptoms and hemorrhagic cystitis.

Answer 15

* 15% of patients with newly diagnosed bladder cancer will have metastases. * Metastases will develop up to 40% of patients within 2 years of having their bladder removed. * Cisplatin-based combination therapy is the preferred approach for them, so offering adjuvant chemotherapy is helpful for those with high risk for reoccurrence. * Neoadjuvant chemotherapy appears to benefit all patients with muscle-invasive cancer prior to having a cystectomy performed. * Chemotherapy is considered for those with bulky lesions or regional metastases.

Answer 16

External Beam Radiation * Delivered in fractions over a 6–8-week period. * 10-15% of patients will develop bladder, bowel, or rectal complications. * 30-70% of patients will have reoccurrence with radiotherapy alone. * Systemic chemotherapy is offered in conjunction with radiation to some patients.

Answer 17

* Immunotherapy consists of drugs called Anti-PDL-1 inhibitors. * These checkpoint inhibitors are approved as second line therapy for metastatic urothelial cancer by the FDA after the patient has received platinum-based chemotherapy. * Immune checkpoints are molecules on certain immune cells that need to be activated or inactivated to start an immune response. * Checkpoint inhibitors don’t work directly on the tumor but allows the immune response that has only started, to progress to full force. * PD-1 is a checkpoint protein on T cells. Normally it is an “off switch” that helps keep the T cells from attacking the other cells in the body. * When PD-1 (a protein on normal and cancer cells) binds to PD-L1, it tells the T cells to leave that particular cell alone. * Some cancer cells have large amounts of PD-L1, which helps them hide from an immune attack. * Monoclonal antibodies that target either PD-1 or PD-L1 can block the binding and boost the immune response against cancer cells.

Answer 18

Examples of PD-L1 inhibitors include: * Durvalumab (Imfinzi) * Avelumab (Bavencio) * Atezolizaumab (Tecentriq) Examples of PD-1 inhibitors include: * Nivolumab (Opdivo) * Pembrolizumab (Keytruda)

Answer 19

* The frequency and progression are correlated with grade. * Progression is more common with poorly differentiated lesions and carcinoma in situ that is associated with papillary bladder cancers. * At initial presentation, 50-80% of bladder cancers are superficial that include stage Ta, Tis, T1. * When properly treated, survival rate is excellent at 81%. * 5-year survival of patients with T2 and T3 diseases are 50-75% after radical cystectomy. * Long term survival is rare for patients with metastatic disease at time of presentation.

Answer 20

* Delirium * Infection * Atrophic urethritis and vaginitis * Pharmaceuticals * Psychological Factors * Excess Urinary Output * Restricted Mobility * Stool Impaction | DIAPPERS

Answer 21

* Detrusor Overactivity/Urge Incontinence * Urethral Incompetence/Stress Incontinence * Overflow Incompetence

Answer 22

* Detrusor overactivity refers to uncontrolled bladder contractions that cause leakage. * It’s the most common cause of incontinence in older adults, accounting for two-thirds of the cases. * In women, they will have urinary leakage after an intense urge to urinate that cannot wait. * Men have similar symptoms but usually their detrusor overactivity coincides with urethral obstruction from benign prostate hyperplasia. * Overactive bladder is characterized by frequency, urgency, and nocturia. * Can present with or without urge incontinence.

Answer 23

* The underlying mechanism of urge incontinence is bladder overactivity, so uninhibited bladder contractions occur during the filling and storage phase. * Most women will not find any type of identifiable pathology. * Some patients as they get older, also have impaired bladder contractility. * This increases the risk of urinary retention by reducing the intravesical bladder pressure in overcoming bladder outlet pressure during bladder contractions, which is now thought to be a function of bladder underactivity.

Answer 24

Pelvic examination: * To test for urge incontinence, have the patient relax her perineum and cough vigorously while standing with a full bladder. The patient may also lay on the table and perform Valsalva test (bearing down as if trying to have a bowel movement). * Delayed leakage of several seconds or persistent leakage suggests that the problem is caused by uninhibited bladder contraction induced by coughing.

Answer 25

* men with BPH and detrusor overactivity * PVR < 150 mL

Answer 26

* Second most common case of established urinary incontinence in older women. * Stress incontinence is most commonly seen in men after a radical prostatectomy. * It is characterized by instantaneous leakage of urine in response to an increase in intra-abdominal pressure. * This can occur along with detrusor overactivity and have a “mixed incontinence.” * Typically has urinary loss with laughing, coughing, or lifting heavy objects.

Answer 27

* The primary issue of stress incontinence is urethral underactivity, related to either decreased tone of the internal urethral sphincter or hypermobility of the bladder neck. * Stress incontinence occurs with elevated intra-abdominal pressure, which causes a sudden increase in the bladder pressure. (Normally these changes are counteracted by contractions of the internal urethral sphincter. Stress incontinence occurs when the bladder pressure is higher than that of the urethra.) * Hypermobility of the bladder refers to displacement of the bladder neck and urethra during increases of intra-abdominal pressure. (Normally this results in the urethra compressed against the muscles of the anterior vaginal wall, which provides support for both the bladder neck and urethra. If the muscles are weak, they can’t provide this support, which displaces them both so incomplete urethral closure and leakage of small amounts of urine occur.) * Stress incontinence is commonly related to vaginal deliveries and hormonal changes associated with menopause in women.

Answer 28

* This occurs when urinary retention leads to bladder distention and overflow of urine from the urethra. * Urethral obstruction (due to prostatic enlargement, urethral stricture, bladder neck contracture, or prostate cancer) is a common cause of established incontinence in older men but rare in older women.

Answer 29

* Overflow incontinence is related to bladder underactivity and/or outflow obstruction. * When the bladder is filled to capacity, the bladder cannot empty due to poor contractility or obstruction around the urethral sphincter.

Answer 30

* abnormal kidney function > 3 mo (GFR < 60 mL/min or proteinuria, or albuminuria) * primary causes are DM, HTN, ASCVD * independent risk factor for CAD * Proteinuric CKD has worse prognosis

Answer 31

* Augmentin : avoid 875mg with CrCl< 30; use 250-500 mg * Amoxicillin: 250-500 mg po q 12 if CrCl< 30 * Clarithromycin: reduce dose by 50% if CrCl< 30 * Ciprofloxacin: reduce 500 mg q 24 hours CrCl < 30 * Levaquin: reduce dose to q 48 hours CrCl < 50 * Bactrim: reduce usually dose 50% CrCl < 30 * Nitrofurantoin: contraindicated GFR < 60? * Metronidazole: adjust CrCl< 10 * Cephalexin * Tamiflu * Allopurinol: reduce 50 mg daily CrCl < 60 * Colchicine: avoid GFR , 30 * Indomethacin: avoid GFR < 60 * Meloxicam: reduce CrCl < 20 * Ibuprofen: avoid GFR < 60 * Naproxen: avoid GFR < 30 * Percocet: reduce dose q 12 if GFR < 30

Answer 32

* NSAIDS, COX-2 * Proton pump inhibitors ( in CKD 4 or later) * Magnesium-containing antacids (tums, Rolaids, Gaviscon, Alka-seltzer) * IV contrast dye * aminoglycoside, vancomycin, trimethoprim/sulfamethoxazole * Digoxin * Over the counter: magnesium citrate!!! * when GFR < 30 caution with most medications

Answer 33

* Yearly BMP, UACR, Lipids * BP < 120/80 ( ace/arb); NA < 1.5 g daily * Statin: moderate intensity pts > 50 yoa GFR < 60ml/min * Low dose asa if low bleeding risk? * Current vaccinations * Remember risk for ASCVD!!!

Answer 34

* BMP * UACR * Lipids * PTH * Ca/Vit D * CBC * Phosphorus

Answer 35

* AV Graft: 2-4 wks to develop; increased risk clot/infection * CVC: immediate use; usually into internal jugular, subclavian, or femoral; temporary use only, don't allow for large volume * AV Fistula: 2-6 mo to form; lower risk of clot/infection; conects an artery to a vein; lasts for years

Answer 36

* Filtration of patient’s blood with a dialyzer; continuous or intermittent * Corrects imbalances of electrolytes, fluids, toxins, and waste * Must leave home 3 x a week * Restricted diet * Can feel “ yuck “ after * In general, refer patients for access before GFR < 15

Answer 37

* Av fistula usually takes 2-6 months to form * Less risk of clots or infection and last for years * Connect the artery to the vein * Surgeon may order vessel mapping to determine size and quality of veins and flow * Affected limb care includes no venipuncture/bp

Answer 38

* If pt has small or weak veins that will not develop into fistula may use a synthetic graft or tube to create connection * Usually needs 2-4 weeks to develop * +/- bruit or thrill * Increased risk clotting and infection; do not often last as long as AV fistula * Limb care includes no venipuncture, BP, heavy lifting

Answer 39

* Flexible, hollow tube inserted into large vein (Internal jugular, subclavian, femoral) * Usually a means for temporary dialysis * High infection rate * Do not allow for large volume – can affect treatment * Veins can develop stenosis or clot * Usually changed every 4 weeks * Swimming/bathing not recommended

Answer 40

* Dialysis via the peritoneum * Does not require vascular access * Less stressful on the patient- decreased side effects, can be done at home * less effective than hemodialysis * Protein loss and increased risk for peritonitis * Requires intra-abdominal catheter- risk infections and adhesions

Answer 41

Polycystin proteins allow calcium influx, which activates pathways in the cell that inhibit cell proliferation; mutations cause cells to proliferate abnormally and start to express proteins that cause water to be transported into the lumen of the cyst, which makes them get larger and larger, compressing the surrounding tissue more and more

Answer 42

DOMINANT * located on non-sex chromosome * s/sx appear between 30-40 yrs RECCESSIVE * s/sx appear shortly after birth or into adolescence

Answer 43

* all are except uric acid stones * struvite are infection stones * cystine stones are genetic (autosomal recessive defect in sodium-dibasic amino acid cotransporter

Answer 44

* AKA coral calculi * usually type of struvite stone * branched stones that occupy large portion of collecting system (renal pelvis + calyces) * can damage the kidney and/or lead to life threatening urosepsis

Answer 45

* Primary hyperparathyroidism (high calcium levels) * Gout (high uric acid) * Hypertension * Diabetes mellitus * Obesity * Inflammatory bowel disease (IBD) * Short gut syndrome * Gastrointestinal bypass surgery * Urinary tract infections (chronic upper urinary tract)

Answer 46

* Upper ureter or renal pelvis: flank pain w/ CVA tenderness * Lower ureter: radiates to labium or ipsilateral testicle

Answer 47

Ureteropelvic junction (UPJ) * Junction of the renal pelvis and ureter Ureter at the pelvic inlet * Site of ureteral crossing of the iliac vessels Ureterovesical junction (UVJ) * Junction of the ureter and urinary bladder

Answer 48

* Made by the kidneys by filtering wastes and extra water from the blood 1-2 L of urine is produced daily * Polyuria: excessive urine output; > 2L/day * Oliguria: output of < 500 mL/day * Anuria: output of 0-100 mL/day Appearance * Yellow color due to urochrome, a pigment from the breakdown of hemoglobin * Variation of color due disease states, hydration status, foods eaten, and medications * Pyuria: pus in the urine; cloudy due to infection * Hematuria: blood in the urine; can be gross or microscopic

Answer 49

* orange: azo/pyridium * fluorescent yellow: excess vitamin B

Answer 50

Odor * Affected by the foods we eat * “fruity” odor: acetone in diabetic patients * “foul/strong” odor: may indicate acute UTI Chemical composition * 95% water and 5% solutes (urea, sodium, potassium, chloride) * Glucose, free hemoglobin, albumin, ketones, and bile pigments in urine are indicators of disease pH * Ranges from 4.5-8.2, but is normally mildly acidic at 6.0 Specific gravity * Ratio of the density of a substance to the density of distilled water * Range from 1.001 (dilute) to 1.035 (concentrated)

Answer 51

* lower: urethritis, prostatitis, cystitis * upper: pyelonephritis

Answer 52

* Urine acidity * High urea concentration * Emptying of the bladder (micturition) * Ureterovesical and urethral sphincters * Mucous secretions: Urethra in ♀, Prostate in ♂ * Protective uroepithelial immune response * Secretion of uromodulin from the kidneys

Answer 53

* Blood enters the glomerulus. The glomerulus filters the blood and decides what to resorb and pass thru kidney ( ions, H20, protein, urea, minerals, vitamins, drugs) and what to not absorb and kick out into the urine. * A normal glomerulus forms a tight barrier which prevents passage/leaking of blood and or protein into the urinary filtrate. When glomerulus is damaged or inflamed the barrier is compromised which allows passage of blood and or protein thru the barrier. This is the earliest sign of glomerular lesion- if left untreated and it progresses eventually the GFR will decline.

Answer 54

**Fenestrated endothelium** * Endothelial cells that look like honeycombs with large pores (70-90 nm) * Small enough to exclude blood cells from the filtrate **Glomerular basement membrane (GBM)** * Size- and charge-selective barrier to the passage of macromolecules from the plasma * Excludes any molecule larger than 8 nm * Prevents negatively charged particles from passing * Albumin is a ~7 nm protein and negatively charged → repelled by the basement membrane **Podocytes of the epithelium** * ~30 nm wide and negatively charged

Answer 55

* Proteinuria if a marker of renal parenchymal and glomerular disease and an independent predictor of progressive kidney disease, cardiovascular disease, and peripheral vascular disease * Albumin is the only measurable protein in urine on a urine dipstick. If have a positive urine dipstick for protein (albumin) you need to quantify with either a 24- hour urine collection or protein-creatinine / albumin-creatinine ratio on a random urine sample * Level of proteinuria is diagnostically helpful to distinguish tubulointerstitial disease vs glomerular disease ( > 3500 mg/g is glomerular disease; > 150mg/g but < 200 mg/g is tubulointerstitial or glomerular disease)

Answer 56

USED TO MEASURE PROTEINURIA * If positive and have retinopathy then diagnosis is diabetic nephropathy * 30-300 mg/g “microalbuminuria” * > 300 mg/g = over proteinuria

Answer 57

hematuria + proteinuria

Answer 58

Pre-renal:low perfusion (60-70%) * Hypovolemia, hypotension Post renal: obstruction to flow (5-10%) * BPH, urolithiasis, outlet obstruction Intrarenal: intrinsic disease (25-40%) * Tubules ( Acute Tubular Necrosis) * Interstitium (Acute interstitial nephritis) * Glomerulus (Glomerulonephritis)- RBC casts!! (if you see RBC cases on UA = damage to glomerulus)

Answer 59

NEPHROTIC * UA: fatty casts, > 3.5 g/d proteinuria, +/- hematuria * preserved absorption of ions, water, creatinine, GFR * sx: generalized + periorbital edema, HTN NEPHRITIC * UA: RBC casts, cola/smoky urine, < 3.5 g/d proteinuria, hematuria * impaired absorption of ions, proteins, water * INCREASED creatinine, DECREASED GFR * sx: edema, HTN

Answer 60

* Children: benign hematuria, henoch-schonlein purpura, mild post-infectious GN, IgA nephropathy, hereitary nephritis * Adults: IgA nephropathy, hereditary nephritis, SLE

Answer 61

* Children: postinfectious GN, membranoproliferative GN * Adults: SLE, membranoproliferative GN, rapidly progressive GN, post-infectious GN, vasculitis