Week 1 (Renal) Flashcards

Question

Ions and osmolality in different compartments

Answer 1

All compartments have **same osmolality** (because water follows solute to maintain osmotic equilibrium) **Intracellular**: **K+**, PO4 **Extracellular**: **Na+**, Cl-

Answer 2

Estimated to **2[Na+]** **Posm = 280-290**

Answer 3

**Effective** solutes contribute to osmolality and **osmotic pressures;** increase in number of solutes causes free water to **move** into their compartment; ex: **Na+, K+, glucose** **Ineffective** solutes contribute to osmolality but not to osmotic pressures; **can cross vascular walls** and cell membranes so **water never has to move** to follow; ex: **urea**

Answer 4

**Osmoregulation**: maintains plasma osmolality (serum [Na+] and cell volume), uses osmoreceptors in **hypothalamus** to stimulate **thirst** and **ADH**, cause urine osmolality and water intake/excretion to change **Volume** **regulation**: maintains effective circulating volume (effective tissue perfusion), uses sensors in **carotid sinus** (SNS, some ADH), **afferent arteriole** (RAAS, glomerular perfusion, GFR), and **atria**/ventricles when severe CHF (ANP when atria stretch/vol exapnds to get RID of water), cause urinary Na+ excretion and thirst Remember, **volume** more important than osmolality!

Answer 5

Use volume regulation! No osmolality change Increased effective circulating volume (ECV) **Suppression of SNS, ADH, RAAS** **Increased ANP** to promote Na+ and water excretion

Answer 6

Use osmoregulation Plasma osmolality decreased **Suppress ADH** to excrete water Urine osmolality decreases (more dilute)

Answer 7

Use both osmoregulation and volume regulation Plasma osmolality increased so water shifts extracellularly (**into blood vessels**/plasma) to **increase effective circulating volume** (ECV) **Increased ADH**, thirst to enhance free water **reabsorption** and **intake** which decreases water excretion and increases urine osmolality Then, **RAAS** **suppressed** and **ANP increases** to cause water excretion

Answer 8

Uses both osmoregulation and volume regulation **Sweat is hypotonic** so plasma osmolality increases and ECV decreases **Increased ADH, thirst, RAAS** **Decreased ANP** Drink fluid equivalent to sweat composition so no electrolyte/volume disturbances! If drink water, will retain free water and become hyponatremic. If drink nothing, will continue to be hypernatremic.

Answer 9

**Palpable** **swelling** due to the **expansion** of **interstitial fluid volume** Common clinical conditions associated with edema: **CHF, cirrhosis, nephrotic syndrome**

Answer 10

**Albumin** in the **blood** maintains oncotic pressure **Lymphatics** take away extra fluid

Answer 11

Alteration in more than one of Starling's forces: 1) **increased** **capillary** **hydraulic** pressure 2) **Increased capillary permeability** 3) **Increased interstitial oncotic** pressure 4) **Decreased plasma oncotic** pressure **Lymphatic obstruction** **Renal Na+** and **water retention**

Answer 12

**Poor CO** --\> **decreased** **ECV** --\> **decreased tissue perfusion** **Increased** **RAAS, SNS, ADH** --\> Na+ and water **retention** --\> **increased** **plasma volume** Early in CHF, this **enhances cardiac contractility and CO** but as disease progresses, continuing accumulation of plasma volume reaches a point where **cardiac contractility cannot be improved** to improve CO so Na+ and water retention causes volume expansion and **edema**

Answer 13

**Edema, hypoalbuminemia, heavy proteinuria (\>3g/day), hyperlipidemia/hyperlipiduria** Hypoalbuminemia due to urinary loss (and maybe altered albumin metabolism) --\> **decreased capillary oncotic pressure** --\> arterial underfilling Also have renal **Na+ retention** due to underlying renal disease (independent of hypoalbuminemia) **Increased RAAS, SNS, ADH** **Increased capillary permeability** (Lp) Altered reflection coefficient of proteins (s) **Administration of albumin** improves renal Na+ excretion and edema (transiently since you're still losing albumin due to renal disease!) because **increases oncotic pressure of plasma** so allows you to get rid of water!

Answer 14

Gradual decrease in plasma albumin would mean gradual decrease in interstitial albumin (why...?) so **oncotic pressure gradient would be minimal** People with **no albumin don't have edema**! **Correction** of renal disease improves Na+ excretion and corrects edema **before hypoalbuminemia is corrected**!

Answer 15

Happens in patients with **cirrhosis** **Portal hypertension** (due to postsinusoidal obstruction from hepatic fibrosis) causes portosystemic shunt that **reduces hepatic metabolism** of vasoactive peptides (prostaglandins, substance P, VIP, glucagon all cause vasodilation!) which causes **vasodilation of splanchnic bed** and **systemic** circulation (also increased NO increased because reduced clearance of bacterial products and this also contributes) Fall in systemic ECV and reduced systemic vascular resistance --\> **Increased RAAS, SNS, ADH** to retain water --\> **heart** **decompensates** and CO decreases --\> **ascites** and **edema** Also with SNS, overdo the **vasoconstriction in kidneys**, **brain**, **liver**, **adrenals** after water IS retained and this causes **kidneys to shut down** due to severe vasoconstriction (not disease of the kidney, it's just that blood isn't going there!) = **decreased GFR = hepatorenal syndrome** Note: **portal** **HTN** causes **splanchnic** **vasodilation** but splanchnic vasodilation makes **portal HTN worse** because of blood pooling!

Answer 16

Clinical condition that occurs in patient with chronic liver disease, advanced hepatic failure, and **portal HTN** characterized by **impaired renal function** and marked **abnormalities in arterial circulation** and activity of **endogenous vasoactive systems**. In kidney there is marked **vasoconstriction** that results in **low GFR**. In **extrarenal** **circulation** there is predominance of arterial **vasodilation** that results in reduction of total systemic vascular resistance and arterial **hypotension**.

Answer 17

**Cirrhosis** with **ascites** Serum **creatinine \>1.5 mg/dl** **No improvement of serum Cr** after \> 2 days with **diuretic** **withdrawal** and **volume expansion with albumin** Absence of shock No current or recent nephrotoxic drugs Absence of parenchymal kidney disease as indicated by proteinuria \>500mg/day, microhematuria \>50 RBC/hpf, and/or abnormal renal UTZ Note: if patient improves with infusion of albumin, it is NOT HRS

Answer 18

**Type I HRS**: \> **doubling** of initial **serum** **creatinine** to **\>2.5 mg/dl** or 50% reduction in **creatinine clearance** to **\<20 ml/min** within 2 weeks; may occur spontaneously but frequently has **precipitating factor** (severe bacterial infection (**SBP**), GI **hemorrhage**, major **surgical** procedure, or acute **hepatitis** imposed on cirrhosis); **shorter survival of 2 weeks** **Type II HRS**: **moderate** and **stable** reduction in GFR; renal failure does not have rapidly progressive course; dominant clinical feature is **severe ascites** with poor or **no response to diuretics**; **longer survival of 6 months**

Answer 19

**Prevention**: infuse **albumin** at dx of SBP; **prophylaxis** for SBP; use TNF inhibitor **pentoxifylline** in those with alcoholic hepatitis; **avoid** **nephrotoxic** agents/NSAIDs/ overdiuresis/large vol paracentesis Use **albumin** to improve intravascular oncotic pressure and mobilize interstitial fluid into **central blood volume** **TIPS**: divert portal blood flow to hepatic vein to systemic circulation; improve variceal bleed; **improve renal perfusion**; complications are bleeding, infection, hepatic encephalopathy and renal failure (due to dyes?) **Vasoconstrictors**: analogues of vasopressin with decreased antidiuretic properties; **terlipressin** (not in US), **octreotide** (inhibits glucagon) + **midodrine**, **NE + albumin**; sometimes **low dose vasopressin** Molecular adsorbent recycling system (**MARS**): combination of kidney and liver dialysis that has an albumin circuit so can remove albumin-bound toxins and water-soluble toxins (however not yet widely available or approved for tx of chronic liver disease) Liver **transplantation**!! Note: renal vasodilators do not work well!

Answer 20

**[Na+] \<136 mEq/L** Most common electrolyte disorder Independent **predictor** of **death** amont ICU and geriatric patients, hear failure acute STEMI, cirrhosis (so need to pay attention to [Na] even though pt might not have symptoms!)

Answer 21

Has nothing to do with total body water or salt imbalance **Falsely high volume**: severe **hyperlipidemia**, **hyperparaproteinemia** (multiple myeloma, Waldenstrom's macroglobulinemia) Extracellular dilution due to extracellular free water shift: **hyperglycemia** (just give insulin to put glucose in cells!), hypertonic mannitol **Mis-measurement** because lots of glucose/mannitol/sorbitol/glycine in blood brings water in but can't measure those things so looks like hyponatremia This doesn't happen anymore!

Answer 22

**Hypoosmolar** state **Hypovolemic**: **sweat**/renal/**GI**/pulmonary blood loss, **third spacing** (acute inflammatory state causes increased vascular permeability so intravascular vol shifts out into interstitial space), **diuretics** (HCTZ), **mineralocorticoid** **insufficiency** (cannot reabsorb Na+, cerebral salt wasting **Euvolemic**: **SIADH**, **hypothyroidism**, **cortisol** **insufficiency**, **psychogenic** **polydipsia**, **tea and toast/beer potomania**, reset osmostat, **pregnancy**, **nephrogenic SIAD** **Hypervolemic**: **cirrhosis, nephrotic syndrome, CHF, renal failure**

Answer 23

Initially you have **low ECV** (due to salt and **water loss** in hypovolemia or due to volume **redistribution** or vasodilation in hypervolemia), so increase **ADH** and **thirst** and **drink** a ton then get hyponatremic! Must be able to **secrete ADH** and must have **free water to drink** in order to get hypovolemic hyponatremia Note: looks like just the starting point that is different between hyper- and hypovolemic...mechanism is the same otherwise?

Answer 24

**Hypothyroidism**: not understood but maybe because **CO down**, renal plasma flow down so **ADH** **upregulated** to retain more water **Cortisol** **insufficiency**: increased **CRH** which is **co-expressed with ADH** (just innocent bystander!) Psychogenic polydipsia: dilution, kidneys can't get rid of it quickly enough **SIADH**: malignancies, drugs affecting CNS (antipsychotics, antidepressants, antiepileptics), CNS problems, pulmonary diseases, N/V, pain, hypoglycemia, NSAIDs, cyclophosphamide **Tea and toast syndrome/beer potomania**: don't eat enough so **don't have enough solute** to make urine so can't get rid of water (kidneys need solute in order to get rid of water) **Pregnancy**: drink lots because **higher thirst** and threshold for **ADH release** is lower **Nephrogenic SIAD**: gain of function **mutation** of ADH receptor so act like ADH always around!

Answer 25

**Hypovolemia** sweat/renal/GI/pulm/blood loss, third spacing: **high** urine osmolality, UNa **\<20** **Hypovolemia** mineralocorticoid insufficiency, cerebral salt wasting, diuretics: **high** urine osmolality, UNa **\>20** **Euvolemia** SIADH/SIAD, hypothyroid, cortisol insufficiency: **high** urine osmolality, UNa **\>40** (pts not retaining salt here!) **Euvolemia** psychogenic polydipsia, tea and toast/beer potomania, reset osmostat, pregnancy: **low** urine osmolality, UNa varies **Hypervolemia** cirrhosis, nephrotic syndrome, CHF: **high** urine osmolality, UNa **\<20** (trying to hold onto Na+) **Hypervolemia** renal failure: urine osmolality similar to **serum** osmolality (cannot concentrate or dilute well), UNa **\>20** (cannot reabsorb Na+)

Answer 26

**Moderate**: lethargy, headache, N/V, muscle cramps, restlessness, disorientation, depressed reflexes **Severe**: seizures, coma, permanent brain damage, respiratory arrest, brain stem herniation, death Risks: severity and rate of change, Na\>125 usually asymptomatic or minimally symptomatic

Answer 27

When you **rapidly increase serum [Na]** and brain cells **shrink** and **demyelinate** **1-2 days**: generalized **encephalopathy** **2-3 days**: **behavioral** **changes**, cranial nerve palsies, progressive **weakness** culminating in quadriplegia with **locked-in syndrome**, possible death Increased risk: malnourished patients, alcoholics, hypokalemic patients, burn victims, elderly women on thiazides, young menstruant women Do not call this central pontine myelinolysis (CPM) because happens other places too!

Answer 28

**5% increase in [Na+]** should substantially reduce cerebral edema Even seizures can be corrected by increase in [Na+] of 3-5 mmol/L **Acute symptomatic**: correct at **1-2 mEq/L/hr for 2-3 hours** or until neurological symptoms resolve **Chronic**: **1/2 mEq/L/hr** **Never exceed 8-10 mEq/L/day** (use lower range for high risk patients)

Answer 29

**Water restriction** in pts that are stable, euvolemic or hypervolemic (don't want to water restrict someone who is dry!) **Salt supplement** with isotonic normal saline in hypovolemic patients; use hypertonic saline in severely symptomatic patients w/severe hyponatremia or SIADH; use salt tablets if euvolemic or if SIADH of malignancy (sad to tell them to water restrict, but good to tell them to eat salty food!) **Increase renal water excretion** in patients who aren't eating make them eat, use **vaptans** to block vasopressin receptor 2, use **furosemide** to make dilute urine Can get hyponatremic encephalopathy if not well oxygenated so make sure patient is **oxygenated**

Answer 30

**Euvolemic SIADH, hypothyroidism, cortisol insufficiency** **Hypervolemic CHF, nephrotic syndrome, cirrhosis** In any of these conditions, if ADH is secreted too much, use vaptans Vaptan: V2R antagonist (blocks action of ADH), aka "aquaretics" because get rid of water and not salt

Answer 31

**Hypovolemic**: treat underlying disorder, give normal saline, discontinue HCTZ if applicable **Euvolemic** SIADH, hypothyroid, cortisol insufficiency: treat underlying disorder, **water restrict,** **salt suppress** if severe Euvolemic psychogenic polydipsia: water restriction Euvolemic tea and toast/beer potomania: increase **protein intake**, consider urea Euvolemic reset osmostat or pregnancy: leave them alone **Nephrogenic SIAD**: same as SIADH except **vaptans** (won't help bc this is gain of function mutation) **Hypervolemic**: treat underlying disorder, **water** **restriction**, **vaptans**, **salt supp** if severe hyponatremia and vaptans not available

Answer 32

Miscalculations Failure to follow serum Na closely (if don't catch disturbance until the next day it is too late) **Unrecognized** **sources** of Na+ (other MD giving Na+, giving K+ causes Na+ to come out of cells and go into vasculature as if giving Na+!) **Excess free water loss** (monitor urine output!): polyuria post pituitary infarction, GC replacement in pts with cortisol insufficiency, pts with central DI not taking ddAVP, excessive GI or skin hypotonic fluid loss, recovery from acute respiratory failure, withdrawal of thiazides during correction of hyponatremia, water deprivation in primary polydipsia, volume expansion with IV fluids

Answer 33

Patient with SIADH has Uosm of **600** Give 1L of 300mM salt but kidneys want to concentrate urine (so much ADH around) Kidney takes 300mosmol salt and 500ml water to create **600mosm** urine! Then have **500ml free water left** to reabsorb! In the end it's like you're giving 500ml free water and making the problem worse! Make sure **osm of fluid is higher than osmolality of urine** or else this will happen!

Answer 34

**K+ into** cells and **Na+ out** K+ into cells and **H+ out**, but H+ does not contribute to osm because buffered, so **water follows K+ into cells**, decreasing intravascular volume K+ and Cl- into cells, and again **water follows K+ into cells**, decreasing intravascular volume If patient hyponatremic and hypokalemic, don't give 200 Na+, give 150 Na+ and 50 K+

Answer 35

**Water diuresis**: nephrogenic DI, central DI, psychogenic polydipsia, pregnancy (vasopressinase in placenta degrades ADH!) **Solute diuresis**: urea, glucose TPN, contrast dye, myoglobin, hemoglobin, mannitol, IV fluids

Answer 36

One of these 3 problems and i**nadequate free water** replacement or **thirst defect**: 1) **Excessive** **administration** **of Na+**: NG feeding without adequate free water, normal saline replacement for hypotonic fluid loss, alkalinization of IV fluids (1 amp bicarb contains 45mEq Na!) 2) **Free water loss**: burn patient/GI/sweat loss of hypotonic fluid, nursing home/debilitate patient, DI + problem with free water access/thirst center, osmotic diuresis (TPN, glucose, urea, mannitol, diuretics, contrast dye) 3) **Intracellular free water shift**: rhabdomyolysis, seizures

Answer 37

If impending **cardiovascular collapse** use **normal saline** If past +/- ongoing salt loss, use D5 1/4 NS, or D5 1/2 NS If need excess **glucose**, use **D10W** If water deprived **nursing home**/debilitated patient, use D5W, D5 1/4 NS (NEVER free water alone!)

Answer 38

**Acute kidney injury**: sudden **decrease in GFR** over **hours** or **days** **Rapidly progressive** renal failure: renal fxn declines **weeks** to **months** **Chronic kidney disease**: renal fxn declines **\>3 months**

Answer 39

Presents as **increase in serum BUN** and **creatinine** and/or **reduction in urine volume** Ongoing research of **biomarkers** but not ready for day to day clinical practice yet (most likely will be urine tests like KIM-1, NGAL) Summary: most commonly diagnosed by change in BUN and/or serum creatinine (look at time course of change and if baseline creatinine not known, use clinical judgment); change in urine volume important mostly for defining prognosis but sometimes may be first manifestation of disease

Answer 40

**Azotemia**: increase in **circulating concentrations** of waste products/nitrogenous substances (viz. urea nitrogen, creatinine) **Uremia**: syndrome of **signs and symptoms** associated with renal dysfunction Every patient with uremia has azotemia, but most patients with azotemia are not uremic

Answer 41

**Risk** of renal injury: creatinine 1.5x baseline, urine output \<0.5 ml/kg/h for \>6 hr **Injury** to kidney: creatinine 2x baseline, urine output \<0.5 mg/kg/h for \>12 hr **Failure** of kidney function: creatinine 3x baseline or \>4mg/dl with increase \>0.5 mg/dl, urine output \<0.3 ml/kg/h for \>24 hr or anuria for \>12 hr **Loss** of kidney function: persistent renal failure for \>4 weeks **End-stage disease**: persistent renal failure for \>3 months Other definitions: risk involves increase serum creatinine of 0.3-0.5 mg/dl over baseline **AKI is first 3 categories ("RIF")**

Answer 42

Duration of renal dysfunction: pre-existing lab data, inpatient or outpatient **Anemia** implies chronic kidney disease (no **erythropoietin**!): normocytic, normochromic anemia in the absence of any other cause of anemia **Kidney size**: small kidneys specific for chronic kidney disease, normal sized kidneys can occur with either acute kidney injury or chronic kidney disease Radiologic evidence for renal **osteodystrophy** or significant **PTH elevation** implies **CKD** Greater the **tolerance** of **azotemia**, longer the time the patient has had kidney disease

Answer 43

Drugs: **trimethoprim**, **cimetidine** inhibit the secretion of creatinine

Answer 44

Urine volume \<0.5 ml/kg/h considered to be reduced Severity of AKI can be determined by presence/absence of **oliguria** (urine output **\<400 ml/day**) or **anuria** (urine output **\<100 ml/day**) Prognosis of oliguric AKI (chance of recovery or death) is substantially **worse** than of non-oliguric AKI Note: if urine volume less than 500, won't be able to stay in fluid balance and will **build up fluids**

Answer 45

**Pre-renal**: GFR falls due to **inadequate renal perfusion** (kidneys perceive low volume so produce less urine to maintain intravascular volume) **Intrinsic renal/renal parenchymal**: involving **glomeruli**, t**ubules, interstitum, or blood vessels** in renal parenchyma **Post-renal**: mechanical **obstruction** to normal flow of urine from kidneys to ureters to bladder and finally through urethra

Answer 46

Hallmark is true or perceived **decrease in perfusion to the kidneys** Causes include: **Hypovolemia**: volume loss (GI, renal, skin), blood loss (GI, MVA) **Cardiac** causes: acute cardiogenic shock, CHF **Liver** **disease**: could be excessive diuretic use, GI bleeding causing vol depletion, hepato-renal syndrome, acute tubular necrosis **Nephrotic** **syndrome**: ineffective intra-arterial volume and not a direct result of underlying disease **Renovascular**: renal venous thrombosis

Answer 47

SIte of injury is **glomerulus, tubulointerstitum, or intra-renal vasculature** Glomerulus: acute **glomerulunephritis** Tubulointerstitial: acute tubular necrosis (**ATN**), acute **tubulointerstitial nephritis**, intra-tubular **crystal deposition** Vascular: vasogenic, microangiopathic hemolytic anemia (**MAHA**), cholesterol emboli

Answer 48

Most common renal **parenchymal** disease that leads to AKI **Ischemic** ATN: causes that lead to pre-renal disease cause ischemic ATN if severe enough or go on for long enough **Toxic** ATN: caused by radiocontrast **dye**, **aminoglycosides**, amphotericin B, cis-platinum, endogenous **myoglobin** (after crush injury) and **hemoglobin** (after intravascular hemolysis) On histology, see **loss of brush border**, some **mitotic** **figures** as cells divide and try to restore themselves After ischemia and reperfusion, lose brush border, lose polarity, then cells undergo apoptosis and necrosis and **obstruct lumen** and **cause backleak of tubular fluid**

Answer 49

Form of **parenchymal** AKI caused by **allergic reaction** to administered **medication** (usually for 5 days or longer) Most commonly caused by **beta lactam** antibiotics (**penicillins**, **cephalosporins**), **PPIs**, **NSAIDs**, H2 blockers Renal dysfunction may be associated with **fever** or other systemic symptoms (**rash**, etc) See **eosinophiluria (\>5%)**

Answer 50

**Parenchymal** AKI caused by precipitation of some sort of **crystals** **Immunoglobulins**/light chains in patients with **multiple myeloma** **Calcium** in patients with hypercalcemia **Uric acid** in people with **tumor-lysis syndrome** **Drug** **crystals** in patients receiving **acyclovir, indinavir, sulphadiazine** **Oxalate** in people who have consumed **ethylene glycol** or **vitamin C**

Answer 51

Can be classified as **pre-renal** or **parenchymal** Functional disorder (reversed by stopping medication) due to **change in vascular tone** Medication-induced AKI: **NSAIDs** cause inhibition of **prostaglandins** which leads to **constriction** of **afferent** arteriole which **decreases GFR**; **ACEi** and **ARBs** inhibit **ATII** which leads to **dilation** of **efferent arteriole** which also **decreases GFR** Also **cyclosporine**/FK506 and **hypercalcemia** constrict afferent arteriole?

Answer 52

**Obstruction** to urine flow leading to backup of fluid in bladder or in kidney Obstruction must be **bilateral**, or unilateral in setting of underlying chronic kidney disease or single functioning kidney Do **US** to see if buildup of urine

Answer 53

**Urine analysis** incuding microscopy Urine **electrolytes** Renal **ultrasonography** **Renal biopsy** if suspect acute glomerulonephritis (rare to do this now though)

Answer 54

**Specific gravity** tells you how **concentrated** the urine is **Dipstick** measures **albumin, blood, leukocytes/nitrate** **Microscopy** shows you cells (**RBCs, WBCs)**, **casts**, **crystals**

Answer 55

Implies **acute glomerulonephritis** Active urine sediment: glomerular **hematuria** (dysmorphic RBCs, RBC casts), generally associated with **proteinuria** Only way to get **red cells** in urine is via **glomerulus** so must be problem with glomerulus causing AKI

Answer 56

In setting of AKI and sterile pyuria, implies **tubulointerstitial nephritis** WBCs present if there is some sort of **inflammation** Most common cause is acute pyelonephritis (**bacteria**), but drugs too??

Answer 57

Remember, usually **no intrinsic damage to kidney** yet Generally benign May see **hyaline** **casts** (but not sensitive or specific for any type of AKI)

Answer 58

**Epithelial cell casts** **Muddy brown casts** This is rare, and occurs when **tubule itself is undergoing necrosis**

Answer 59

**Pre-renal** (incl HRS): urine **vol** **decreased**, **sp gr \>1.02**, **Uosm** **\>500**, **FENa \<1%**, FEurea \<35%, FEuric acid \<7%, urine sediment has **hyaline casts** **Intrinsic** **renal**: variable urine volume, **sp gr 1.01**, **Uosm \<350**, **FENa \>2%**, FEurea \>35%, FEuric acid \>15%, other urine sediment

Answer 60

FENa is **percentage of filtered sodium that is excreted** In health (**normal** GFR): **\<1-2%** **Pre-renal: \<1%** **Intrinsic renal \>2%** **FENa = [(UNa/PNa)/(UCr/PCr)] x 100** = [(UNa/UCr)/(PNa/PCr)] x 100 Considerations: urine volume (**oliguric**/non-oliguric) because normal FENa = pre-renal FENa!, false + FENa, **diuretics** (use **FEurea** instead because diuretics tell you not to reabsorb Na+)

Answer 61

For overwhelming majority of clinical settings, decision making about distinction of acute vs. chronic, and potential causes is made on clinical grounds **Rarely used** to diagnose AKI Renal biopsy imperative in presence of **urine sediment** Know someone has **glomerulonephritis** but want to know **how to treat it**?

Answer 62

Specifically **ATN**: **Initiation**: don't get **BUN/creatinine increase** until after time of injury; creatinine, eGFR poorly related to actual renal function **Maintenance** **Recovery**: may be **polyuric** Time course generally lasts **3-10 days**, may be up to 12 weeks

Answer 63

Correct underlying disease if possible: improve renal perfusion (give **fluids** or **improve** **cardiac** **function**) if pre-renal, **relieve** **obstruction** if post-renal, give **steroids** +/- **cytotoxics** for glomerulonephritis If **ATN** or underlying causes not treatable, treatment is **supportive**: monitor fluids to prevent volume overload, manage metabolic complications, avoid nephrotoxics, know when to dialyze! Agents to prevent or ameliorate course of parenchymal AKI have not been effective

Answer 64

**Unremarkable**: **pre-renal AKI** **RBCs** in urine, dysmorphic: **glomerulonephritis** **Granular** casts, **epithelial** casts, cellular debris: **ATN** **WBCs**/WBC casts: **pyelonephritis**, **interstitial nephritis** (if WBCs are **eosinophils**) or **glomerulonephritis** **Eosinophiluria**: allergic **interstitial nephritis** or **cholesterol emboli** **Muddy brown** casts: acute tubular necrosis **(ATN)**

Answer 65

**Absolute** indications for dialysis: **CHF despite diuretics**, unable to medically manage **hyperkalemia** and **metabolic** **acidosis**, **pericarditis**, **encephalopathy**, signs/symptoms (severe volume overload where you need intubation or O2, etc..?) **AEIOU**: acidosis, electrolytes (hyperkalemia), ingestion/intoxication, overload of fluid, uremia Dialyze BEFORE any of these complications develop though (waiting for appearance of these is unacceptable!)

Answer 66

Occurrence of AKI **increases death risk** in patients with multi-organ failure in the ICU, in-hospital mortality may approach 80% In patients who **survive**, renal function recovers in most, but even if serum creatinine normalizes, there is underlying **scarring** and GFR does not normalize Also patients who survive are at higher risk for subsequent development of **chronic kidney disease** and **end-stage renal disease** **Prevention** is always better but not always possible

Answer 67

**Pre-renal azotemia** and **ATN** comprise up to 80% of all causes of AKI Need to distinguish between pre-renal azotemia and ATN!

Answer 68

**Parietal epithelial cells** of Bowman's capsule (protect us from outside world!) **Bowman's space** (this is outside environment!) **Visceral epithelial cells** (contain **podocytes**/foot processes that partially cover BM and spaces btwn are bridged by slit diaphragms) **Basement membrane** (is outside of either endothelial cells of capillary or mesangial cells) **Endothelial cells** (fenestrated) **Capillary lumen** Note: **mesangial** **cells are** inthe middle, contacting either BM or endothelial cells at all times

Answer 69

**Support** the capillaries and endothelial cells Like **stroma** (support), modified smooth muscle cells/pericytes Consists of **matrix** and **mesangial cells** Mesangium contiguous with media of arterioles Mesangial matrix material is similar to basement membrane material (both **stain** **silver**!) Mesangial cells have **contractile** function, **phagocytic**, **proliferate**, secrete **biologic** **mediators**, produce **mesangial matrix**

Answer 70

In the glomerulus, endothelium is only partially surrounded by mesangium Where mesangium is absent, the endothelium is surrounded by glomerular basement membrane So, endothelium supported by either **mesangium** or **basement membrane**

Answer 71

**Subepithelial** deposits: between **epithelial cells** (which have podocytes) and **BM**; usually have **less inflammation**; are father out **toward Bowman's capsule** **Subendothelial** deposits: between **endothelial cell** (fenestrated, right by capillary lumen) and **BM**; usually have **more inflammation**; closer in **toward capillary lumen**

Answer 72

**Collagen Type IV** (forms a network to which other proteins attach: **laminin**, **proteoglycans**, **fibronectin**) **6** different collagen IV **alpha** **chains** which combine in various forms to produce collagen Type IV **triple helices** (building blocks of GBM)

Answer 73

Composed primarily of **nephrin** a transmembrane protein whose extracellular portion extends between the foot processes but intracellular portion connects to **podocin**, **CD2AP**, and **actin cytoskeleton** This whole thing is one unit and comprises part of the cytoskeleton

Answer 74

**Focal**: involving **\<50%** of glomeruli **Diffuse**: involving **\>50%** of glomeruli **Segmental**: involving a **portion** of a glomerulus **Global**: involving **most** of a glomerulus

Answer 75

**Hypercellularity** (used to be called proliferation) **BM thickening** or **duplication** **Sclerosis**: closure of capillary loops, solidification **Hyalinosis**: insudates of plasma proteins that become trapped in areas of scarring; **glassy**, **pink** **eosinophilic** stuff **Crescents**: cellular proliferation in Bowman's space (macrophages, neutrophils, epithelial cells, fibrin); usually due to **BM rupture**; seen in severe glomerular injury

Answer 76

1) In situ **antibody antigen reactions** (antibody against **intrinsic** glomerular antigen or against **planted** antigen (that got into glomerulus from elsewhere)): **Type II hypersensitivity** reaction 2) Deposition of **circulating** **antibody antigen complexes**: **Type III hypersensitivity** reaction 3) **Cytotoxic** **antibodies** 4) **Cell mediated immunity** 5) **Soluble mediators** (complement, cytokines, etc)

Answer 77

Use **immunofluorescence** to detect and characterize (IgG, IgA, IgM, C3, etc) Use **EM** for precise **localization** of deposits (subepithelial vs. subendothelial)

Answer 78

If process of forming ICs is **transient** then deposits are **phagocytized** and/or **degraded**; inflammatory changes resulting from deposits resolve --\> **patient gets better** If process is **continuous**, disease is **chronic** and get progressive glomerulonephritis --\> **dialysis, death** or **transplantation**

Answer 79

**Nephrotic** syndrome **Acute nephritic** syndrome Rapidly progressive glomerulonephritis (**RPGN**) **Asymptomatic** hematuria and proteinuria **Chronic renal failure**

Answer 80

**Nephritic**: inflammatory process (variable combo of neutrophils, lymphocytes and macrophages in capillary loops); **hematuria** (capillary wall injury), **RBC** casts, **azotemia**, **oliguria**, **hypertension**, mild **proteinuria** (\<3.5g/day) **Nephrotic**: **edema, hypoalbuminemia, hyperlipidemia/**hyperlipiduria**,** massive **proteinuria (\>3.5g/day)** Note: in nephrotic syndrome, the holes in the podocytes allow proteins to go through and leak out, but don't allow cells to go through, so no RBCs in nephrotic syndrome!

Answer 81

**Nephrotic** syndrome Most common cause of nephrotic syndrome in **adult** **caucasians** Antibody reaction to antigens located on **epithelial cells** (**Type** **II**): Ags may be **intrinsic** to epithelium (phospholipase A2 receptor on visceral epithelial cell = primary/idiopathic) or **planted** on epithelial cell after crossing BM (**bacterial** or **viral** antigens (syphilis, schistosomiasis, malaria, Hep B, rarely Hep C), **malignancy** (lung, colon, breast, melanoma), **rheumatic** disease (lupus, scleroderma), **inorganic** **salt** (gold), some **drugs** (captopril, penicillamine)) **Subepithelial** deposits, then with progression get segmental and global **sclerosis** LM: **thickened** **GBM** (epithelial cells respond to injury by making more BM); see **"stubble"** because BM spikes are dark and deposits are light IF: **granular** deposits of IgG and complement along BM EM: **"spike and dome"** appearance of new BM with spikes (podocytes) forming between subepithelial deposits Prognosis: variable course, proteinuria in 60%, progressive renal disease in 40%, renal failure in 2-20 years

Answer 82

**Nephrotic** syndrome Most common cause of proteinuria in **children**, but can occur at any age Lipoproteins in urine, follows viral infection, associated with Hodgkin's lymphoma LM: **normal** glomeruli EM: **foot process effacement** IF: negative Tx: **steroids** (don't need to take biopsy to treat)

Answer 83

**Nephrotic** syndrome More common in AA and hispanic, risk is obesity **Hematuria** and **hypertension** usually seen Can be **primary** (idiopathic) or **secondary** as a component of glomerular ablation nephropathy (**nephron loss** leading to **hyperfiltration** of remaining glomeruli) or **congenital** (mutation in nephrin or podocin), or secondary to other glomerular diseases; **soluble mediator** in serum has been identified FSGS recurs **after transplantation** in 10-20%, can recur within 24-48 hours, recurrence rate higher in patients who had aggressive disease in native kidney IF: negative, no ICs EM: negative, no ICs Prognosis: 50% of patients in renal failure in 10 years Tx: prevent recurrence after transplantation with aggressive **plasmapheresis** (get rid of soluble mediator)

Answer 84

AKA mesangiocapillary GN Usually **nephrotic** but can present as **mixed** nephrotic and nephritic Pathogenesis: **ICs** from serum sickness, deposits can trigger/fix complement, recruit inflammatory cells **Mesangial proliferation** (reaction to deposits) and capillary wall abnormalities --\> large glomeruli, "lobular accentuation" of glomerular tuft, hypercellular Thickening of capillary walls due to massive **subendothelial deposits** Double contoured (**"tram-track"**) capillary walls due to migration of mesangium into capillary wall in reponse to subendothelial deposits Can be primary (idiopathic): **IgG** and **complement** deposits; more common in **children** Can be **secondary** due to **infections** (infected shunts, Hep B, Hep C) or **lupus**: **IgG** and any combination of **IgA, IgM, and complement;** more common in **adults** IF: **granular** deposits along loops and in mesangium Prognosis: 30-40% progres to **chronic renal failure**

Answer 85

AKA **dense deposit disease** (DDD) Similar presentation to idiopathic (Type I) MPGN: **nephrotic** or **mixed** In children and young adults; **not** associated with hepatitis or bacterial infections or lupus; **not** associated with circulating ICs Pathogenesis: activation of alternate complement pathway; **mutations** in **complement** components, **Abs** which interfere with various complement components resulting in inappropriate activation, anti-complement factor H or B; in **children** usually **mutation** in complement and in **adults** usually **autoantibody** **BM thickened** by **ribbon**-like deposits; complement present in **irregular** **granular** and **linear** distribution, variable **mesangial cell proliferation** and **inflammatory cell component** Difference from Type I is that get **intramembranous** very **dense** IC deposits in BM **Decreased serum C3** but normal C1 and C4

Answer 86

**Nephritic** syndrome **IC deposits** trapped in glomerulus (bind/fix complement, leukocytic infiltration, proliferation of mesangial, endothelial and epithelial cells) that can be caused by **exogenous** antigens (**post-infectious/**poststreptococcal) or **endogenous** antigens (**lupus**) **Poststreptococcal GN** is one type Can also get it from **staphylococcus, Hep B, plasmodium (malaria), treponema (syphilis)**

Answer 87

**Nephritic** syndrome Type of **acute proliferative glomerulonephritis** Group A (Strep pyogenes) beta hemolytic strep (strains 12, 4, 1) **1-4 weeks** following **skin** or **pharyngeal** infection (latent period correlates with time required for production of antibodies against strep organism) **Diffuse** **global** GN and glomeruli full of **neutrophils** (swollen endothelium, occasionally segmental fibrinoid necrosis, rarely see crescents) **IgG** and **complement** on capillary walls and in mesangium; **starry sky pattern** (less uniform than in membranous nephropathy); subepithelial **lumpy-bumpy** pattern plus some **subendothelial** and **mesangial** deposits on EM Prognosis: most **children** **recover** but 15-50% of **adults** develop **end stage renal disease**; deposits resolve within a few months, no scarring in most cases, biopsy not performed if diagnosis certain

Answer 88

**Nephritic** syndrome Most common primary glomerular disease worldwide; more common in Asian and hispanic but uncommon in AA Often follows **URI** or **GI** **infection**; most present with **hematuria** or **proteinuria**; 10% present with nephrotic syndrome Related to **Henoch Schonlein purpura** Pathogenesis: **IgA Ab/Ag complexes** trapped in **mesangium**; abnormal IgA production and clearance (increased IgA production in bone marrow); only **50% have increased serum levels** of IgA; increased incidence in twins; increased incidence with **celiac** **disease** and **liver** **disease** (liver can't clear IgA Ab/Ag complexes from intestines); **abnormal glycosylation** may reduce plasma clearance of IgA LM: **mesangial** **proliferation**, **segmental sclerosis**, **crescents** IF: **mesangial** **deposits** EM: deposits, **mesangial** **matrix** (both under BM but in mesangial cell, so not called subendothelial) Prognosis: 25-30% develop **renal failure** over 20 years; rarely aggressive

Answer 89

**Systemic IgA syndrome** due to IgA deposition in multiple organs Skin: **purpuric rash** GI: abdominal pain, **bloody diarrhea** Joints: **arthritis** Kidney: **IgA nephropathy** Note: cannot diagnose Henoch Schonlein purpura by kidney biopsy--need to look at entire patient and see IgA vasculitis elsewhere

Answer 90

**Nephritic** syndrome **Mutation** in **Type IV collagen** causes **glomerulonephritis**, **deafness** and **eye** problems Variable inheritence; mutations in alpha 3, 4, 5 chains of collagen Type IV; X-linked, AR or AD inheritance Variability in collagen deletion leads to **variability** in clinical presentation/severity LM: variable and nonspecific; progressive glomerular sclerosis IF: negative EM: **alternately** **thick** and **thin** BMs; thick areas have irregular lamination of lamina densa (**"basket weave"** pattern)

Answer 91

**Nephritic** syndrome Some siblings of Alport's patients have this (in others it is sporadic); females in families with X-linked disease **Non-progressive microscopic hematuria only**

Answer 92

**Nephritic** syndrome A **clinical** syndrome (rapidly deteriorating renal function over days to weeks) and if untreated have irreversible loss of renal function Various causes/disease associations: **Goodpasture's** syndrome, **Wegener's granulomatosis**, **microscopic polyangitis** LM and IF: all (**\>50%**) glomeruli have **crescents** (severe glomerular injury almost always due to ruptured capillary loop BMs, contain **fibrin** in Bowman's space, macrophages, epithelial cells, and plasma proteins like **C3b**; may see platelets walling off **ruptured BM**) Note: if disease is not rapidly progressive (so not classified as RPGN) then just presents with nephritic syndrome

Answer 93

1) **Anti-GBM disease** (10-15%): **Goodpasture's** syndrome (linear IgG deposits on capillary walls by IF but not EM, tx with plasmapheresis to remove pathogenic Ab) 2) **Circulating immune complex mediated disease** (45%): **IgA** (Henoch Schonlein purpura), **MPGN**, **lupus**, **postinfectious**, rarely membranous nephropathy; plasmapheresis does not help 3) **Pauci-immune** (45%): nothing seen on IF; most patients have **+ANCA** (**microscopic** **polyangitis** = pANCA/anti-MPO; **Wegener's granulomatosis** = cANCA/anti-proteinase 3)

Answer 94

1) **Focal segmental glomerulosclerosis** (FSGS): as nephrons die, the **surviving** ones have to **work harder** and become damaged; compensatory **hypertrophy**, **increased** blood flow/**filtration**/transcapillary pressure, **injury** to endothelial and epithelial cells, **protein accumulation in mesangium** --\> triggers proliferative and inflammatory mediators which cause injury to epithelium --\> proteinuria; segmental scarring and eventually **global** **scarring** --\> **decreased GFR** --\> vicious cycle 2) **Tubular atrophy and interstitial fibrosis**: glomerular scarring causes scarring of tubules because efferent arteriole cannot supply blood to tubulointerstitum so causes **ischemia** and **inflammation** and **scarring** --\> inflammation induces fibrosis and that **entraps** next tubule over --\> tubule scarring causes sclerosis of the upstream glomeruli --\> severe **proteinuria** and **vicious cycle**

Answer 95

1) **Post-infectious GN** 2) **Lupus** 3) **Membranoproliferative glomerulonephritis (MPGN)** Note: lots of things that cause GN do not have low C3, but if you DO find low C3, must be one of these

Answer 96

**Alkalinize** urine to solubilize myoglobin **Mannitol** and **saline** to enhance excretion of myoglobin Keep patient **hydrated** to flush out myoglobin Obtain urine electrolytes prior to treatment to provide insight into diagnosis Diuretics and dye studies (nephrotoxicity) contraindicated

Answer 97

Triad: 1) **Microangiopathic hemolytic anemia** 2) **Thrombocytopenia** (low platelets) 3) AKI (**uremia**)

Answer 98

**Muscle** **wasting** and **cachexia**: decreased creatinine production --\> **increases** ratio **Rhabdomyolysis**: spills creatinine into the blood --\> **decreases** ratio **Dehydration**: induces urea reabsorption --\> **increases** ratio High **dietary** protein: increases BUN --\> **increases** ratio **GI** **bleeding**: increases urea production as RBCs are broken down in the intestine --\> **increases** ratio **Liver** **disease** --\> decreased urea production because no urea cycle --\> **decreases** ratio

Answer 99

**NSAIDs**: block effect of prostaglandins, **constricting** **afferent** arteriole to decrease GFR; acute interstitial nephritis (AIN), nephrotic syndrome, renal papillary necrosis **ACEIs**: block effect of angiotensin II, **dilating** **efferent** arteriole to decrease GFR; acute interstitial nephritis (AIN), membranous glomerulonephropathy, immune complex glomerulonephritis, acute tubular necrosis If taking **both ACEI** then **NSAID**, can develop **pre-renal azotemia** because very low GFR!

Week 1 (Renal) Flashcards

(123 cards)