Week 2 (Renal) Flashcards

Question

Respiratory alkalosis

Answer 1

**Hypoxemia**: pulmonary disease, CHF, high altitude **Direct stimulation** of respiratory center: gram-negative septicemia, hepatic failure, psychogenic, pregnancy, neurologic disorders (stroke, pontine tumors) **Mechanical ventilation**

Answer 2

Patient with **severe** **vomiting** (metabolic alkalosis) also has uncontrolled **insulin** **dependent** **diabetes** mellitus with ketoacidosis (metabolic acidosis) and may have additional **lactate** production from the **hypovolemia** causing reduced tissue perfusion (ALL CAUSE **metabolic acidosis**). Finally, there will be a **respiratory** **compensation** with hyperventilation (**respiratory** **alkalosis**)

Answer 3

A **loss** in **GFR**, often accompanied by **albuminuria** and caused by a variety of diseases, that is persistent (**\>3mo**), typically **slowly** **progressive** and **irreversible** Its manifestations, which are often **minimal in its early stages**, reflect the loss of renal homeostatic, metabolic, and endocrine and excretory functions

Answer 4

1) **Obstructive** uropathy, chronic **glomerulonephritis**, chronic **interstitial** **nephritis**, **diabetic nephropathy**, **hypertension**, **congenital** 2) Inexorable **loss of nephrons** and renal function 3) Homeostatic, metabolic, endocrine, excretory 4) **Uremia** Note: **elevated** **urea is NOT the cause of symptoms!** It's byproducts of protein metabolism, but uremia used as catchall phrase to describe signs and symptoms of CKD (particularly neurologic manifestations) because of ease of measurement and because historically mistakenly thought of as cause of manifestations of CKD

Answer 5

Stage 1: normal GFR (\>90 ml/min; 120 ml/min), persistent albuminuria = kidney damage with normal filtration Stage 2: GFR 60-89 ml/min, persistent albuminuria = kidney damage with mildly decreased filtration Stage 3: GFR 30-59 ml/min = moderately decreased filtration Stage 4: GFR 15-29 ml/min = severely decreased filtration Stage 5: GFR \<15 ml/min = kidney failure Note: nothing new is happening in later stages, it's just a **progression**

Answer 6

The stage in the evolution of CKD (**4** and **5**) when adaptive mechanisms become inadequate to avoid **morbid** and potentially **life-threatening clinical manifestations** Preparations for alternative supportive therapy (dialysis, transplantation) are required or death will ensue Note: good news that patients aren't sick at the beginning even though losing lots of GFR, but also bad news because **lose a lot of GFR without having symptoms** so don't come to get treatment until later stages

Answer 7

**Diabetes** 40% **Hypertension** 28% Clomerulonephritis 12% Polycystic disease 3% Urologic 5% Unknown 12% Note: approximately 50% of patients present with ESRD without a proven diagnosis

Answer 8

**Reduced** **nephron** **population** or **DM --\>** glomerular **hypertension** and/or **metabolic** and **genetic** factors --\> cause glomerular injury --\> **glomerulosclerosis** --\> systemic hypertension and further decrease in total GFR --\> intraglomerular **hypertension** --\> vicious cycle Other mechanisms of how intraglomerular HTN causes glomerulosclerosis: **Endothelial damage** and **microaneurysm** formation cause **intraglomerular** **thrombosis** which causes fibrosis and liberation of plateled derived growth factors (**PDGF**) --\> **glomerulosclerosis** and **mesangial expansion** Increased mesangial traffic of macromolecules causes mesangial expansion which causes **glomerulosclerosis** Increased number of macrophages causes liberation of **growth factors** which causes increased **hyalin** formation and **mesangial** **expansion** --\> **glomerulosclerosis**

Answer 9

In health, we can eat as much salt as we want because can make very dilute or very concentrated urine = have high salt ceiling and low salt floor However, in **CKD**, kidney's capacity to both **retain** **salt** and **get** **rid** of it gets **worse** = ceiling gets lower and floor gets higher --\> if eat too much salt will get **hypernatremia** and/or **volume** **expansion** since ADH still working (maintain osmolality but cannot get rid of excess salt) Note: some people with CKD commit suicide by eating lots of bananas because cannot excrete K+!

Answer 10

**MSK**: renal **osteodystrophy**, muscle weakness, decreased growth in children, amyloid arthropathy due to beta2-microglobulin deposition **Hematologic**: anemia, platelet dysfunction **Electrolytes**: hyperkalemia, metabolic acidosis, edema, hyponatremia, hyperphosphatemia, hypocalcemia, hyperuricemia **Neurologic**: **encephalopathy**, **peripheral neuropathy** **Cardiovascular**: hypertension, pericarditis **Endocrine**: carbohydrate intolerance due to insulin resistance, hyperlipidemia, sexual dysfunction (incl infertility in women) **GI**: anorexia, nausea, vomiting

Answer 11

Patients with any degree of CKD have a substantial increase in **cardiovascular** **risk** that can be explained in part by an increase in traditional risk factors (**HTN**, **DM**, **anemia**) as well as non-traditional risk factors (**inflammation**/vascular **calcification**) Probability of coronary artery **calcification** increases as time on dialysis increases (so need to get people transplanted) **30yo** patient on **dialysis** has same risk of **cardiovascular** **mortality** as **80yo** in general population

Answer 12

**"Rugger-jersey" spine**: alternating sclerosis and porosis Absorption of distal clavicle

Answer 13

**Infection** Urinary tract **obstruction** **ECF volume depletion** **CHF** **Hypertension** **Nephrotoxins** **Pericardial effusion** **Hypercalcemia** **Severe hyperuricemia**

Answer 14

Treat reversible causes of renal dysfunction Prevent or slow progression (**ACEI/ARB,** diet) **Treat HTN** Limit proteinuria Prevent and treat complications Identify and prepare patients requiring **renal replacement therapy** in a timely fashion

Answer 15

No intervention --\> **death** from uremia **Hemodialysis** (HD): in **center** (go 4h for 3x per week) or at **home** **Peritoneal** dialysis (PD): CAPD/CCPD; need lots of training to do this so don't want to make someone go through it if will just be short term Kidney **transplantation**: living donor, deceased donor

Answer 16

**CO2** **dissolved** is dissolved in the **plasma** = **concentration** **pCO2** is is a **gas** (in the lungs?) = **partial pressure** CO2 dissolved is in **equilibrium** with pCO2 pCO2 (mmHg) x **0.03** = CO2 dissolved (concentration)

Answer 17

You can buffer with HCO3, but you can also **increase ventilation** (blow off CO2) In the calculation, you **don't add "x" to the numerator** or the CO2 dissolved since you'll just blow that CO2 off with increased respiration

Answer 18

**90%** is reabsorbed in **PCT** and **10%** is reabsorbed in **collecting tubule** **HCO3-** in tubular lumen combines with H+ that has been secreted --\> **H2CO3** --\> **carbonic** **anhydrase** turns that into CO2 and H2O --\> **CO2** diffuses into **PCT** (or collecting tubule) cell Inside the **PCT** cell is **negative** because of **Na/K ATPase**, and that causes **Na/3HCO3- pump** to be active in pumping those ions back into **peritubular capillary** Because of this, the CO2 that diffused into that cell is converted by **carbonic** **anhydrase** to HCO3- and is **reabsorbed** back into peritubular **capillary** Note: similar process for reabsorption in collecting tubule cell but what creates negative charge there is excretion of H+??

Answer 19

Most of this happens in **collecting** **tubule** (only some in PCT) Aldosterone stimulates **H+ ATPase** to secrete H+ from collecting tubule into tubular lumen --\> H+ combines with filtered **HPO4** and is excreted as H2PO4- This system is exhausted fast since only a **limited** amount of **phosphate** is **filtered**

Answer 20

**Ammonia** can **freely** cross into tubular lumen, and comes from most importantly **PCT** but also **collecting** **tubule cell** (intercalated Type A cell) Slightly more complex in that NH4+ partially reabsorbed in loop of henle, converted back into NH3 and then resecreted in collecting tubule lumen where is converted to NH4+ to get rid of acid **H+** from collecting tubule combines with NH3 to create ammonium (**NH4+**) and is excreted because ammonium is **trapped** and can no longer get back into cells

Answer 21

1) **Increased** **GFR** 5 years after onset of T1DM, when **nephropathy** begins (may be due to increased volume due to glucose, may be due to growth factors?) --\> begin to get **microalbuminuria** as well 2) **Hyperfiltration** 3) Damage to remaining nephrons causes **fall in GFR** and damage to GBM --\> microalbuminuria turns to **heavy** **proteinuria** 4) At this point, have 20-30 years until **kidney failure** (used to be called 20 year renal retinal syndrome, but now we can treat them)

Answer 22

With fewer nephrons, the diseased kidney **filters** **much** **less** Na+ than usual but still excrete the same amount but **secreting a higher percent** In advanced renal failure, have very **high FENa** to stay in salt balance!

Answer 23

Thrombocytosis with platelets \> 1,000,000 **Elevated serum** K+ but **normal plasma** K+ Due to excessive **cellular release** of K+ during **blood clotting** If put sample into tube with **no heparin**, you allow cells to **clot** which causes release of K+ (this is **serum** K+) If put sample into tube with **heparin**, **prevent clotting** and prevent release of K+ from cells (this is **plasma** K+) No therapy necessary, and in fact it is bad if you try to "treat" the patient

Answer 24

Leukocytosis with WBC \>100,000 Elevated plasma K+ but normal serum K+ Fragile white cells more susceptible to in vitro **destruction** during **centrifugation** when they are freely suspended in the plasma If put sample into tube with **no heparin**, you allow cells to **clot** so the cells **cannot** **lyse** and get **no release of K+** (this is **serum** K+) If put sample into tube with **heparin**, **prevent clotting** and cells can **lyse** and have **release of K+** from cells (this is **plasma** K+) No therapy necessary

Answer 25

With **thrombocytosis** you get increased K+ **during clotting** so if you prevent clotting by adding heparin, you'll see actual K+ in **plasma** With **leukocytosis** you get increased K+ **during** **centrifugation** due to cell lysis so if don't add heparin, you allow clotting, just take the **serum** and get actual K+

Answer 26

In vitro **hemolysis** Due to **mechanical** **trauma** during venipuncture Know its due to hemolysis because serum has **reddish** **tint** due to release of hemoglobin from red cells

Answer 27

1) Extrarenal causes due to redistribution 2) Renal causes Note: very hard to get hyperkalemia by eating too much K+

Answer 28

Diabetics get **hyperkalemia** because have no insulin and **insulin** usually **stimulates Na/K pump** to pump K+ into cells

Answer 29

**Beta blockers** **Digoxin** (Lack of insulin)

Answer 30

In metabolic acidosis, have too much H+ in the blood, so you bring **H+ into the cell** but must exchange that for **K+ out** K+ leaves cells and enters bloodstream so get **increased K+ in blood** (LOOKS like hyperkalemia) but **normal overall K+**

Answer 31

In **lactic** **acidosis**, too much **H+** and **lactate-** in bloodstream **Lactate follows proton** from blood into cell to TRY TO maintain electroneutrality Still have to kick out **some** **K+**, so get a little increased K+ in the blood (but not as much as in non-lactic acid-metabolic acidosis)

Answer 32

When **plasma** is **hyperosmolar**, water shifts out of the cells, but **water drags K+** with it due to **friction** Remember, way more K+ inside cells than outside cells, and at this point (less water inside cells), **chemical gradient** higher than electrical gradient so K+ exits cells

Answer 33

**Tumor lysis** **Rhabdomyolysis** **In vivo hemolysis** K+ stored in cells so any process that leads to cell necrosis causes hyperkalemia

Answer 34

Yes, **decreased urinary K+** excretion by kidneys can cause **hyperkalemia** by many mechanisms: **Hypoaldosteronism** causes hyperkalemia because **cannot excrete K+** **Aldosterone receptor blockers** **Voltage-dependent secretory defect** **Diminished ECV** **Renal failure** (GFR \<10)

Answer 35

**Type IV renal tubular acidosis**: hyperkalemia, low renin, low aldosterone; common in patients with diabetic nephropathy of chronic interstitial nephritis **Primary adrenal insufficiency**: hyperkalemia, decreased aldosterone production, low cortisol **Drug-induced** hypoaldosteronism: **NSAIDs** (usually stimulate renin production, but **decreased** renin causes decreased aldosterone), ACEI (inhibit ATII, inhibit aldosterone), **ARII-receptor blocker**, **heparin** (including LMW heparin toxic to adrenal gland so inhibit aldosterone), **beta** **blocker** (inhibits renin and thus aldosterone production) Note: usually aldosterone causes Na+ channels to reabsorb Na+ from lumen, leaving negative charge behind due to Cl- which causes K+ to leave the cell and be excreted

Answer 36

**Spironolactone** **Eplerenone**

Answer 37

Remember that K+ is secreted because **Na+ reabsorption** creates **negative** charge in the lumen so **K+ wants to go out** So impairment in cortical collecting tubule Na+ reabsorption causes inability of K+ to be excreted, causing **hyperkalemia** **Type 1 RTA** (hyperkalemic form of Type 1; defect in Na+ reabsorption) Drugs: **bactrim**, pentamidine, K+ sparing diuretics which block Na+ channel (**amiloride**, **triamterene**)

Answer 38

Leads to **increased** **proximal** Na+ and water **reabsorption** This causes decreased Na+ and fluid delivery to **distal** K+ secretory site, so **less K+ excretion** since Na+ reabsorption and K+ secretion **linked** here

Answer 39

If in renal failure and GFR **\<10** ml/min: **Decreased K+ filtration** Diminished Na+ and fluid delivery to distal K+ secretory site so **less K+ secretion**

Answer 40

**Peaking** of T waves **Flattening** of P waves **Prolongation** of PR interval **Widening** of QRS complex (to sine wave) **V-fib** or cardiac arrest Note: these things happen if K+ \>6 or 7

Answer 41

Give **Ca2+ (calcium gluconate)** to antagonize hyperkalemic actions on cardiac membrane Drive extracellular K+ into cells: **insulin** (glucose to prevent hypoglycemia), **NaHCO3**, beta agonist (albuterol) Remove K+ from the body: diuretics (**lasix**, not ACEI or spironolactone), **kayexalate** (cation exchange resin which does Na+ exchange for K+ across the gut with no fluid loss and in fact Na+ retention causes volume expansion; use if hypovolemic), **dialysis** if severe (hemodialysis better than peritoneal for clearing K+)

Answer 42

Remember, **leukocytosis** can cause pseudohyper AND pseudohypo! **Cells uptake K+ in vitro** Can prevent cellular uptake by rapid **separation** of plasma from cells or by storage of blood in **fridge** to slow metabolic activity

Answer 43

1) **Extrarenal** causes: characterized by K:creatinine ration **\<13** meq/g creatinine (kidneys **trying to conserve K+**) 2) **Renal** causes: characterized by K:creatinine ratio **\>13** meq/g creatinine (**renal K+ wasting**)

Answer 44

Decreased **K+ intake** Increased **sweat losses** **Redistribution** (cells to blood) Increased **GI losses**

Answer 45

**Alkalemia** (H+ out of cells and K+ in) **Insulin** (causes K+ to go into cells) Elevated **beta** **adrenergic** activity (epi, albuterol/beta-agonists cause K+ to go into cells via 3Na/2K pump) Marked increase in **blood** **cell** **production** (**folate** replacement causes cell production and those cells take up K+ to cause hypokalemia)

Answer 46

**Increased** distal **delivery** of **Na+** to collecting tubule will lead to **increased K+ secretion** **Diuretics** **Vomiting** **Proximal RTA** **Osmotic diuresis** (DKA) **Postobstructive diuresis** Diuretic phase of **ATN** **Mineralocorticoid excess** states

Answer 47

**Block the Na/K/2Cl pump** in the thick ascending loop of henle --\> cause **hypokalemia** due to increased loss of K+ and **hypercalciuria** because can't reabsorb Ca2+ as well Mechanism of these findings: usually Na/K/2Cl pump brings those ions in from lumen and K+ is recycled back out to lumen creating **positive charge in lumen** and Cl- reabsorbed all the way to peritubular capillaries creating **negative charge in capillary** --\> this gradient causes **Ca2+, Na+ and Mg2+ to be reabsorbed** from lumen to capillary --\> but since no more gradient when you have loop diuretics that block that Na/K/2Cl pump, don't absorb as much Ca2+ and instead get hypercalciuria Loop diuretics cause **metabolic alkalosis** Loop diuretics cause **hypovolemia** which causes secondary **increased** **renin** and **increased aldosterone**

Answer 48

Block Na/Cl cotransporter from bringing ions in at the distal convoluted tubule --\> **hypokalemi****a**and**hypocalciuria** Can cause hypokalemia because less Na+ reabsorption..?? Drop in intracellular Na+ because less Na+ reabsorbed, and this causes Na+ to be put into cells from blood, which in turn causes **Ca2+ reabsorption** because of Ca/3Na exchanger on capillary side --\> see hypocalciuria Thiazides used in people with **kidney stones** to stimulate Ca2+ reabsorption Also get **hypovolemia**, then **increase** **renin** and **increase** **aldosterone**

Answer 49

Both are mineralocorticoid excess states where you have too much aldosterone, but need to figure out etiology! Key is renin: **primary** has **decreased** **renin** and **secondary** has **increased** **renin** Both have **hypokalemia**, **metabolic** **alkalosis** (H+ secretion stimulated by aldosterone), high aldosterone **Primary** hyperaldosterism because of **adrenal adenoma, bilateral adrenal hyperplasia** (low renin in response to too much volume retention) **Secondary hyperaldosteronism** because of **renal artery stenosis** (high renin to try to "get volume up" since kidneys/afferent arterioles see low perfusion), seen in diabetics, those with arteriosclerosis

Answer 50

Can switch to **K+ sparing** diuretic (**spironolactone**, aldactone) if on thiazide or loop diuretic Can also use spironolactone/aldactone if primary hyperaldosteronism to block aldosterone action Can replace **KCl** Use **amiloride** or **triamterene** (block Na+ channel to block K+ secretion) if volume overloaded and used lasix and became hypokalemic

Answer 51

**Cystic** diseases: simple cysts, dialysis associated cysts, inherited syndomes (autosomal dominant, autosomal recessive), cystic renal dysplasia Acute tubular necrosis (**ATN**) Tubulointerstitial nephritis: **drug induced interstitial nephritis**, acute **pyelonephritis**, chronic pyelonephritis, reflux associated pyelonephritis **Obstruction** (hydronephrosis)

Answer 52

**Acquired** cysts: simple (majority), dialysis associated **Developmental**: renal dysplasia **Hereditary** cystic syndromes (ADPKD, ARPKD)

Answer 53

Single or multiple Most 1-5cm (rarely 10cm) Lined by single layer of **cuboidal** **epithelium** but as cyst expands, this becomes **atrophic** and **flattened** Usually **cortical** No clinical significance other than the fact you have to distinguish them from tumors Usually **incidental** finding but rarely present with pain due to bleeding and expansion

Answer 54

Patients with end stage renal disease, on prolonged dialysis Cysts in cortex and medulla, not particularly big Very rarely you can get adenomas and **carcinomas** within these cysts **Bleeding** may cause hematuria Pathogenesis: **obstruction** of tubules by **fibrosis**; is only dialysis related in that dialysis keeps patient **alive long enough** for cysts to form

Answer 55

5-10% of renal failure Two genetic causes: **PKD1** = polycystin 1 (cell membrane protein responsible for cell-cell and cell-matrix interactions; 85%); **PKD2** = polycystin 2 (cell membrane protein that is a Ca2+ channel; 10-15%) **PKD1** develop end stage disease more **rapidly** than PKD2 High penetrance Need **mutations** in **both** alleles (either PKD1 OR PKD2, not one of each) to get cyst formation, but you **inherit one** germ line mutation and acquire a **later somatic mutation** Abnormal interaction of tubular epithelial cells with surrounding matrix (may trigger increased prolif of epithelial cells resulting in cystic dilation) Cells lining cysts have high proliferation rate and immature phenotype ECM produced by linig cells is abnormal Cysts detach from tubules and enlarge by fluid secretion (which contains mediators which enhance secretion and induce inflammation) Massive **enlargement** with time, up to 4kg, slowly expanding cysts destroy intervening parenchyma, normal renal function for decades then present with renal failure **Extrarenal** manifestations: 40% have **liver** cysts (mostly asymptomatic but occasionally cause obstruction/destruction of intrahepatic biliary tree leading to ESLD), rare cysts in **lung** and **pancreas** (inconsequential), **berry aneurysms** in circle of Willis cause death from subarachnoid hemorrhage 5-15%, **mitral valve prolapse**, sigmoid **diverticulosis** Variably sized cysts, early on parenchyma between cysts normal but then undergoes fibrosis and atrophy causing obstruction and inflammation

Answer 56

Polycystin 1 and 2 form **heterodimer** so malfunction of either results in same phenotype: abnormal **Ca2+** enters when heterodimer messed up --\> problems with cellular **proliferation, apoptosis, interaction with ECM, secretory function**

Answer 57

Present in **infant/child,** is extremely **rare** PKHD1 gene with product **fibrocystin**; expressed in kidney, liver, pancreas; transmembrane protein, extracellular domain has Ig-like structure; most patients **compound heterozygotes** Serious dysfunction at birth, most have **liver** cysts also **Enlarged** kidneys with numerous cysts in cortex and medulla, dilated elongated channels virtually replace cortex and medulla On histology see **cylindrical dilation** of collecting ducts: nearly all ducts involved, all nephrons involved, renal failure **rapid**; cysts lined by cuboidal cells

Answer 58

Most common cause of abdominal mass in newborn; this is **developmental** problem, have persistence of fetal **lobar** organization; abnormal structures (**cartilage**, undifferentiated **mesenchyme**, immature **collecting** **ducts you** usually see during pregnancy only!) Variable degree of atrophy and cyst formation and not all cases are cystic Can be unilateral or bilateral Abnormal **metanephric** differentiation (**NOT premalignant**, just arranged badly) Nearly all cases associated with anomaly of **urinary** **tract** (ureteropelvic junction (UPJ) obstruction, ureteral agenesis/atresia) **Obstruction** in incompletely developed kidney results in abnormal differentiation of mesenchymal elements

Answer 59

**Medullary sponge kidney** **Nephronophtisis** (medullary cystic disease complex)

Answer 60

Injury to **tubular epithelial cells** and/or persistent, severe disturbances in blood flow Acute diminution or loss of renal function (kidneys stop making urine, creatinine shoots up) Most **common** cause of acute renal failure, but is **reversible** Caused by **ischemia, toxic injury, obstruction** **Ischemia** causes **reduced GFR** --\> intrarenal **vasoconstriction** --\> reduced **glomerular** blood flow --\> reduced blood flow to **tubules**

Answer 61

Extensive **surface area** which is highly charged for reabsorption **Transport** system for ions and organic acids Capability to carry out concentration Blood supply by **efferent** arteriole

Answer 62

**Loss of polarity**: redistribution of membrane proteins from basolateral surface to luminal surface This causes decreased Na+ reabsorption which causes **increased Na+ delivery** to distal tubules which through macula densa/JGA induces RAAS causing **vasoconstriction** at glomerular level which results in further decrease in blood flow to **tubules**

Answer 63

**Necrotic** epithelial cells sloughed into lumen and may **clog** tubules (decreases GFR) Loss of epithelial cells allows fluid to **leak** across basement membrane into interstitum (increased interstitial pressure further decreases blood flow) Injured epithelial cells elaborate **cytokines**

Answer 64

**Patchiness** of injury along nephron (especially with toxins that are reabsorbed by one type of PCT cell but not others) Profound dysfunction of epithelial cells (structural alterations) but **doesn't KILL** the cells High capacity to **replace** cells that were lost Note: ATN used to be fatal but now put patient on **fluids, dialysis** for short time and they go home!

Answer 65

Proliferation of epithelial cells (cytokines and growth factors elaborated by injured epithelial cells and inflammatory cells): EGF, TGF-a, IGF, hepatocyte growth factor

Answer 66

Note: histologic severity does **NOT** **correlate** well with degree of dysfunction; different types of ATN preferentially damage diff parts of tubules and some causes of ATN have specific histo features and others don't (most don't) Ranges from mild to extensive necrosis with tubular rupture **Skip areas** (injury may be specific to certain portion of the nephron (toxins)) Attenuation/**loss of brush border** **Thinning of epithelial cells** **Vacuolization** Sloughing of necrotic cells (**necrotic** material in tubular **lumen**) **Mitotic** figures/reactive nuclear changes **Edema** Mild **mononuclear inflammation** Casts: **hyaline**, **granular** pigmented material, varying degrees of **Tamm-Horsfall proteins** (normal urinary glycoprotein) and **plasma proteins**

Answer 67

**Mercuric chloride:** nuclear inclusions **Carbon tetrachlorid**e: accumulation of neutral lipids **Oxalosis**: primary or secondary, have numerous oxalate crystals **Light chain cast nephropathy** (**myeloma** kidney): cracked casts and giant cells

Answer 68

**Primary** **oxalosis**: mutation in **gene** in **TCA cycle** that results in oxalic acid in serum which deposits in kidney and can destroy kidney; presents in infancy; get liver transplant to treat because even though **liver** looks normal, have biochemical abnormality in TCA cycle; little glomeruli and **expanded Bowman's space** since tubules **clogged** with oxalic acid and necrosis, so as glomerulus kicks out fluid, BS expands **Secondary oxalosis**: from **ethylene glycol**, rhubarb leaves

Answer 69

**Drug-induced interstitial nephritis** (most common) **Acute** infectious pyelonephritis **Chronic** pyelonephritis **Reflux associated** pyelonephritis Acute cell mediated **allograft rejection** Terms: interstitial nephritis is noninfectious; pyelonephritis is bacterial infection (but still tubulointerstitial!); both can be acute or chronic Note: glomeruli are uninvolved until late in disease

Answer 70

**Drugs** and **toxins** cause interstitial **immunologic** **reaction**, NOT direct toxicity Direct injury to tubules usually results in ATN, not interstitial nephritis

Answer 71

Caused by synthetic penicillins (**methicillin**, ampicillin), **sulfonamides, rifampin, thiazide diuretics, maybe NSAIDs** Symptoms begin **15 days** after exposure: **fever**, **eosinophilia**, **rash** (25%), **hematuria**, mild **proteinuria**, acute renal failure (particularly in elderly) Treatment: do not biopsy to diagnose, just **stop drug** right away and put patient on **steroids**

Answer 72

Interstitial **edema** Interstitial **infiltrate**: mononuclear cells, **eosinophils** and neutrophils, **granulomas**, lymphocytic tubulitis (**lymphocytes** which cross basement membrane), tubules look farther apart than usual, have inflammatory cells and edema between them Variable degree of tubular **necrosis**, **rupture** and **repair**

Answer 73

**Idiosyncratic** reaction (not dose related) Increased **IgE** in some patients: delayed type I hypersensitivity **Granulomas**: type IV cell mediated response Drug is reabsorbed, binds to tubular cell protein or matrix protein: acts as **hapten**

Answer 74

"Chinese" herb nephropathy, "Balkan" nephropathy Weeds producing aristolochic acid contaminate food Now used as herbal weight loss preparation Patients present in **chronic renal failure**: interstitial fibrosis with minimal inflammation Increased risk of **transitional cell carcinoma** of kidney and urinary tract

Answer 75

**Suppurative** inflammatory process due to bacterial infection Most associated with **UTI** (ascending pyelonephritis) **Hematogenous** spread: seeding of kidney by organisms in blood stream

Answer 76

Only small % of UTIs result in pyelonephritis Risk from UTI associated with **repeat UTI**, **instrumentation**, anatomic anomalies, **congenital** or acquired **E. coli** most common organism, but als **Proteus**, Klebsiella, Enterobacter and Psuedomonas Colonization of lower urinary urethra is fist step: instrumentation and just being a **woman** (shorter urethra, hormonal changes affect bacterial adherence, traumatic injury from sexual intercourse, prostatic fluid antibacterial) Note: **men** have **longer urethra** and antibacterial **prostatic fluid** (more protected from UTI than women)

Answer 77

Multiplication of organisms in bladder: continual **flushing** and **voiding** decreases chance of bacterial growth, postvoid residual urine allows growth **Outflow obstruction**: prostatic hypertrophy, tumors, stones **Bladder dysfunction**: spinal cord injury, diabetic neuropathy **Vesicoureteral reflux**: incompetence of vesicoureteral valve allows reflux of urine into ureters; can be due to **congenital** defects (shortening of intravesicular portion of ureter so don't close it off as well), **infection** (bacterial products decrease contractility of bladder wall), **spinal cord injury** (atony of bladder) **Upper and lower poles** more often involved by pyelonephritis because **papillae** at poles have **flattened** **concave** tips (intrarenal reflux) so more susceptible to backflow of urine, papillae in mid zones pointed convex tips so are resistant to backflow (however, this just means poles affected first...eventually will get everywhere)

Answer 78

Patients with **systemic** **bacterial** **infection** may develop pyelonephritis via **arterial** **spread** of bacteria resulting in **scattered small abscesses** throughout the kidneys Get multiple tiny abscesses everywhere when infection comes in through aorta and renal artery

Answer 79

**Patchy interstitial inflammation**, more prominent in medulla (ascending): neutrophils, lymphocytes, macrophages, tubular lumens filled with **neutrophils** (most specific feature), tubular necrosis, abscess formation if untreated (destruction of tissue) Note: do not do biopsy to determine if pt has pyelonephritis, this is a clinical diagnosis

Answer 80

**Papillary necrosis** (more common in diabetics, obstruction) **Pyonephritis**: pelvis filled with puss/**neutrophils** (obstruction) **Perinephric abscess**: infection and inflammation spread into perinephric fat (diabetics)

Answer 81

**Reflux** **associated**: may be clinically silent, present with renal failure or nephrotic syndrome (secondary FSGS due to subclinical nephron loss), may present with signs of acute pyelonephritis **Chronic obstruction**: extensive overlap in pathogenesis and histology Ex: child has congenital abnormality, gets veiscoureteral reflux, slowly knock off nephrons, child gets bigger so nephrons get increased load, then develop **FSGS** secondarily --\> get 13 year old presenting with **nephrotic** **syndrome** of segmentally **sclerotic** glomeruli w/background of **extensive fibrosis** Note: if there is **no scarring**, most likely **primary** FSGS

Answer 82

Increases susceptibility to **infection** If unrelieved, hydronephrosis develops (obstructive uropathy) Can **occur anywhere**: posterior urethral valve stricture, prostatic hypertrophy, tumors in blader, stones in ureter/bladder interface, tumors compressing/inside urethra, infections of urethra, tumors in pelvis Variability in presentation and severity and outcomes due to **sudden** vs. **insidious** onset, **partial** vs. **complete** obstruction, **unilateral** vs. **bilateral** obstruction

Answer 83

Results in **dilation** of pelvis and calyces, atrophy or renal parenchyma **GFR reduced** but may continue after obstruction Backflow into kidney increases pressure in collecting tubules and gluid can diffuse into interstitum and then into venous and lymphatic vessels (GFR can continue) Medullary vasculature becomes compressed Decreased medullary function and **inability to concentrate** urine Triggers **inflammation** then **fibrosis** **GFR decreases** with time Get only **mild** dilation when obstruction is **sudden** and complete because **GFR impaired sooner** so don't get so much fluid buildup Get lots of **dilation** and **atrophy** when obstruction is **incomplete** or **intermittent** because **GFR less impaired**

Answer 84

May be **cause** or **result** of **renal disease** Complex and multifactorial pathogenesis (genetic and environmental) **95% idiopathic** (essential, primary) **5% secondary** (**renal** or **adrenal** cause)

Answer 85

**Rare** but **treateble** form of **secondary HTN** **Atheromatous** **plaque** at origin of renal artery **Fibromuscular dysplasia**: more common in women, have intimal/medial/adventitial forms, single constriction or a series of constrictions, clinically similar to essential HTN, angiogram for dx; this is NOT related to atherosclerosis

Answer 86

**Renal artery stenosis**: decreased blood flow so decreased pressure in afferent arteriole so **increased renin** and **increased Na+ reabsorption** **Pheochromocytoma**: adrenal medullary tumor releases **catecholamines** which cause **vasoconstriction**

Answer 87

Severe HTN: **\>200/120** **5%** of hypertensive patients have severe and rapid rise in BP and will **die in 2 years** if not treated Most commonly seen in patients with **preexisting benign (low grade) hypertension**

Answer 88

**Blood volume** **Na+ content** Vascular resistance: primary **arterioles** (neural and hormonal control) **Cardiac output**

Answer 89

**Renin/angiotensin**: increase vascular **tone**, increase distal tubular **absorption of Na+** **Antihypertensives** made by kidney: **NO, prostaglandins** Decrease in blood volume detected in kidney: decreased **GFR** results in increased Na+ reabsorption **Natiuretic** factors: made by heart, **inhibit Na+ reabsorption**

Answer 90

Few **single** **gene** examples of essential HTN Most cases represent **cumulative** effects of several genes and environment **RAAS** **Decreased** **Na+ excretion** **increased vasoconstriction** **Structural changes** to vessel walls

Answer 91

**Stress, obesity, smoking, physical inactivity, heavy salt consumption**

Answer 92

HTN causes injury to **large** and **medium** sized vessles **accelerating atherogenesis** **Small** vessel disease is histologically distinct from large vessel disease: **hyaline** **arteriosclerosis** (hyalinosis = trapped plasma proteins), **hyperplastic arteriosclerosis**

Answer 93

Homogenous **pink**, **glassy thickening** of arterioles Loss of structural **detail** (whole wall replaced with hyaline) **Narrowing** of lumen Due to **leakage** then **accumulation** of **plasma** across endothelium **Excess** **matrix production** by smooth muscle cells in media **Arteriolar** **hyalinosis**: insudates of **plasma proteins** fill arteriolar wall resulting in decreased **luminal diameter** and decreased **contractility** Causes: **chronic** **low grade HTN**, but not just HTN: **diabetes**, **aging**, chronic calcineurin inhibitor toxicity (**cyclosporin**, FK506 = **tacrolimus**) Results in **glomerulosclerosis** through **ischemia**, glomerular **scarring** results in loss of entire nephron, small foci or scarring replace nephrons, and **contraction** of kidneys through scarring

Answer 94

Diagnostic term used to describe the changes in the kidney due to **long term benign (low grade) HTN** Increasing incidence with **age, HTN, AA, diabetics** More frequent **renal failure** in AAs, diabetics, paeitns with more severe elevation of BP **Small foci** of **scarring** from **small vessel** injury: foci of **tubular atrophy** and **interstitial** **fibrosis**, glomeruli have **wrinkled** **tufts** due to **collapsed loops,** BS filled with collagen, periglomerular fibrosis **Hyaline arteriosclerosis** Small arteries have medial hypertrophy, **duplication** of elastic lamina **Granular cortical surface** due to small foci of scarring

Answer 95

Seen in more **severe** elevations of blood pressure: **malignant** **hypertension**, **concentric** **lamination**/thickening of arterial walls, progressive **narrowing** of arterial lumens, smooth muscle cell **hypertrophy** and **hyperplasia**, thickened **reduplicated** **BM** **Fibrinoid** **necrosis** in severe examples

Answer 96

Usually seen in patients with underlying benign HTN, **glomerulonephritis**, **scleroderma**, higher frequency in AAs and men Pathogenesis: **injury** to **arteriolar** walls, increased **permeability**, **endothelial** **injury**, endothelial **cell death**, **platelet** **aggregation**, **thrombosis**, **hyperplasia** of intimal cells (narrowing of lumens), **ischemia** (elevated renin) Small **petechial hemorrhages** on surface (due to ruptured arterioles), **fibrinoid** **necrosis** of arterioles and glomeruli (**early lesion**, eosinophilic granular material fills lumen and infiltrates wall, no or minimal inflammation) **Onion** **skinning** (**later** **lesion**) of arterioles: intimal **thickening** through **proliferation** of concentrically arranged smooth muscle cells, thin layers of **collagen** (basement membrane), layers of pale staining material (**"mucoid intimal proliferation"**) of **proteoglycans** and **plasma proteins** **Glomerular** involvement: early (**fibrin** in capillary lumens, **capillary** **microaneurysms**), later (**double** **contoured** capillary loops bc new layers of basement membrane), **ischemic** **wrinkling**, collapse of glomerular tuft (from arteriolar occlusion)

Answer 97

**Thrombosis** in arterioles and capillaries throughout the body, related to **hemolytic anemia, thrombocytopenia, renal failure** Malignant HTN can give picture like this, need to take hx to determine **Adult HUS**: verotoxin releasing bacteria, antiphospholipid syndrome (Lupus), pregnancy/contraceptives, drugs (chemo), radiation, scleroderma renal crisis (malignant HTN), familial HUS, idiopathic TTP, malignant HTN **Childhood HUS**: verotoxin releasing bacteria (E. coli O157:H7, which is on cheeseburgers, apple juice, spinach and bean sprouts) **Familial HUS** TMA morphology: similar to malignant HTN, **thrombi** in arterioles and glomeruli, **swollen** **endothelial** **cells**, subendothelial **fibrin**, **cell fragments**, **mesangiolysis** (disruption of BM/mesangial connection results in **capillary microaneurysms**), with time new BM material produced (see **multiple layers of BM**) by endothelial cell (if it survived) and get **double contours** ("splitting") because of damage to endothelial cells (due to HTN or bacterial toxicity in case of HUS)

Answer 98

**Endothelial** **injury**: denudation of BM exposes **thrombogenic** **collagen**, reduced production of **antithrombotic** **substances** by injured endothelial cells, triggers thrombosis **Platelet** **aggregation**: von willebrand factor **multimers** secreted by endothelial cells, are large and **must be cleaved** into smaller multimers, large multimers induce **aggregation** (if cannot break down multimers because of **loss of proteases**), congenital or acquired loss of specific proteases result in abnormally **large** **multimers** and **thrombosis**, **TTP** (many of patients deficient in ADAMTS-13, a **metalloprotease**)

Answer 99

Advanced renal disease in **40%** of diabetics Clinical syndromes: **nonnephrotic proteinuria, nephrotic syndrome, chronic renal failure** HTN in diabetics increases the risk of developing **diabetic nephropathy** **Microalbuminuria**: 30-300 mg/day of albumin, develops within a few years of diabetes **Overt** **proteinuria**: \>300 mg/day develops in 50% of diabetics within 12-22 years, followed by **end stage renal disease** within **5 years** in many patients

Answer 100

**Glomerular** lesions, **tubular** lesions, **vascular** lesions, **pyelonephritis** (papillary necrosis, perinephric abscesses) **Thickened** capillary loop **BM**: changes begin within few years of onset, early changes only on EM, **progressive**, simultaneous thickening of **tubular BMs** Diffuse **mesangial** **sclerosis**: mesangial expansion due to **increased** **matrix**, mild mesangial **cell** **proliferation** early in disease, with progression expansion of mesangial areas becomes **nodular**, progressive expansion **correlates** with deterioration of renal function **Nodular** **glomerular** **sclerosis**: **mesangial** **expansion** by matrix appears **nodular**, mesangiolysis often seen (disruption of sites at which capillaries are anchored to mesangium results in **capillary** **aneurysms** (distension of capillary loops due to intraglomerular pressure)), nodules expand and eventually **obliterate** **open** **loops**, **Kimmelstiel-Wilson** lesions, seen in **25%** of patients with diabetic nephropathy **Good glycemic control** slows development of diabetic nephropathy, **pancreatic transplantation** can reverse many of the changes

Answer 101

**Hyalinosis** in glomeruli **Trapped plsama proteins** in capillary loops: **fibrin caps** (misnomer because not fibrin) **Insudates** in Bowman's capsule BM (**capsular drops**)

Answer 102

Formation of **advanced glycation end products (AGE)** Activation of **protein kinase C** **Intracellular** **hyperglycemia** with disturbances of polyol pathways **Glycosylation** of **matrix** **proteins**: abnormal matrix-matrix and matrix-cell interactions, decreased endothelial cell **adherence** to **BM** (allows increased fluid filtration (**hyalinosis**)), glycosylated proteins are more **resistant** to **proteolytic** **degradation** (decreased removal of abnormal proteins), glycosylation of BM may cause other **proteins to bind** **Circulating** **proteins** modified by **AGE residues** **Proteins** with **AGE** residues bind to AGE receptors on numerous cell types and induce production of **cytokines, growth factors, proinflammatory molecules**

Answer 103

**Proteins, albumin**

Answer 104

Special types of metabolic acidosis: **lactate, ketones, uremia, intoxication with salicylate, methanol, ethylene glycol, paraldehyde** (overall remember MUDPILERS) **Decreased K+, Ca2+, Mg2+** **Increased albumin** **Alkalosis** (neutral albumin shifts to albumin -)

Answer 105

**Decreased albumin** concentration (2.5 mEq/L decrease in AG for every 1g/dL decrease in albumin concentration) **Increase in K+, Ca2+, Mg2+, lithium, bromide** **Multiple myeloma** (cationic Ig: para-proteins)

Answer 106

**Methanol** intoxication causes **metabolic gap acidosis** due to **formic acid** (which is also toxic) Causes **blindness** then **death**

Answer 107

**Ethanol** intoxication, **isopropyl alcohol** intoxication, **mannitol** intoxication and **glycine** administration

Answer 108

**Methanol** intoxication **Ethylene glycol** intoxication **Ketoacidosis** **Lactic acidosis** **Chronic renal failure**

Answer 109

**Multiple** **myeloma** causing **proximal renal tubular acidosis**

Answer 110

**Multiple myeloma** Patients given **IVIG** (contains maltose)

Answer 111

Toxic \>40-50 mg/dL **Tinnitus** --\> **vertigo** --\> **N/V** --\> **seizure** --\> **death** In early phase get **hyperventilation** (**respiratory alkalosis**) Blocking oxidative metabolism --\> **metabolic acidosis** because of accumulation of organic acids Treat with IV **bicarb** or **hemodialysis** for severe cases

Answer 112

RBC casts indicate **acute glomerulonephritis** unless proven otherwise Both are indicative of glomerular process

Answer 113

This protein is produced in thick ascending limb of loop of henle and is the **matrix** for all urinary **casts** (like **glue** that other cells that sloughed off stick to) If no cells, you can get **hyaline casts** that are just pure Tamm-Horsfall proteins

Answer 114

**Coarsely granular casts** mean sat around for a while (can't tell what kind of cells they are, just that they've been sitting for a while) **Finely granular casts** also sat around and **waxy casts** sat around for longest

Answer 115

**Change in eGFR vs. time** See progressive decline in eGFR due to CKD, but if AKI then see abrupt drop too

Answer 116

**Glomerular**: **significant** proteinuria (\>1,000 mg/day; HMW protein that gets through because of GMB damage), **dysmorphic RBCs** or **RBC casts** **Tubular**: **minimal** proteinuria (\<1,000 mg/day; this is LMW proteins that are normally filtered but now cannot be reabsorbed in PCT because tubules are damaged), **muddy brown casts** (only see this if get urine right away, might not be there the next day), **bland urine**

Answer 117

**Fish oil** (antiinflammatory and reduces mesangial proliferation) **Hypertension control** **ACEI or ARB** **Glucocorticoids** (if acute only?) **Alkylating cytotoxic agents** if progressive disease?

Answer 118

**BP control** **RAAS inhibitors** (ACEI, ARB, if neither of those then mayb RI) Maintain serum **bicarb \>22** (chronic metabolic acidosis can interfere with bone and muscle metabolism, can induce interstitial inflammatory changes that make kidney disease progress faster; give **NaCHO3** or sodium bicitrate) Diabetics maintain **HbA1C \<7%** **Avoid NSAIDs** (especially long-acting ones like aleeve because those worse for kidney)

Answer 119

**Acute**: acute presentation, significant **symptoms**, **hyperkalemia**, normal to **large** kidneys, **normal hb/hct** **Chronic**: chronic history (of not feeling well for a few months), **vague** symptoms, **normo**- to hyperkalemia (gut tries to compensate and secrete K+), **small** to normal kidneys, **low hb/hct**, significant **bone disease**

Answer 120

Early in disease diabetics have **hyperfiltration** so have lots of blood in kidney and they get **enlarged** Toward **end** of disease, kidneys **sclerose** and **shrink down** but end up being about **normal sized**

Answer 121

**Peritubular cells of kidneys**

Answer 122

Kidney stones = renal calculi More common in men, age 20-30 Renal colic due to kidney stones in ureter is **horrible pain** Present with flank pain and hematuria (micro or macroscopic) Calcium stones (70%; are made of calcium oxalate), struvite stones (15%; made of Mg2+, NH4+, PO4 and usually in UTI with Proteus or Staph that convert urea to ammonia), uric acid stones (5-10%; radiolucent and associated with gout and leukemia (rapid cell turnover with uric acid production)), cystine Mostly due to idiopathic calciuria (high Ca2+ for unknown reason) but can form in those with high Ca2+ due to hyperparathyroidism, sarcoidosis, or due to bowel resection (cannot reabsorb bile acids so more bile acids excreted in gut --\> bile acids bind Ca2+ in the gut, so now oxalate cannot bind as much Ca2+ to get excreted in the gut --\> oxalate reabsorbed and filtered into urine and higher levels of oxalate being excreted in the urine and can bind Ca2+ and cause precipitation of Ca2+ stones)

Answer 123

Polycythemia (EPO) Hypercalcemia (PTHrP) Hypertension Liver dysfunction Feminization or masculinization Cushing syndrome Leukemoid reactions Amyloidosis

Week 2 (Renal) Flashcards

(147 cards)