Kidney Water Flashcards

Question

Urothelial (transitional cell) Carcinoma orgin occurs in associated w/ presenting symotoms

Answer 1

orgin in the urothelium lining the renal pelvis adults Associated w/ urothelial carcinoma or dyplasia elsewhere in urinary tract ("Field effect") Symotoms: _Hematuria_, urinary obstruction, hydronephrosis, flank pain

Answer 2

**_Papillary_**: Exophytic mass w/ fronds **_Flat_**: Reddened or granular appearance

Answer 3

**Papillary**: vascular cores; lined by malignant urothelial cells; low or high grade **Flat**: No paillary growth; cells disordered; Non-invasive/high grade - "carcinoma in situ"

Answer 4

Males \> Females 50-80 Cigarette smoking (\*\*Most important); Chemical carcinogens (napthylamine); Infectious agent (_Schistosoma haematobium_ \*Egypt/Sudan) - assciated w/ SCC _Hematuria_

Answer 5

_Hematuria_, dysuria Diagnosed with **urine cytology**: less invasive; cannot easily diagnose low grade malignancy Cystoscopy with **biopsy** is used to more definitively diagnose, however it is more invasive

Answer 6

T: presence and extent of invasion into the bladder wall, involvement of adjacent structures N: Presence/absence of lymph node metastases M: Presence/absence of distant metastases T1: invaded lamina propria T2: Invaded muscularis T3: Invaded soft tissue

Answer 7

**Transurethral resection**: appropriate for low grade, non-invasive papillary lesions **Bacillus Calmette-Guerin (BCG)**: attenuated form of TB, topically administered. Used for high grade, non-invasive lesions, carcinoma in situ. Immunotherapy: incites _granulomatous_ inflammatory response. **Radical cystectomy**: For tumors invading the muscularis (T2) or more, or carcinoma in situ not responsive to BCG **Chemotherapy**: for advanced cases

Answer 8

Intravascular fluid (1/4 ECF) Interstitial fluid (3/4 ECF)

Answer 9

Plasma tonicity reflects concentration of solutes that do **NOT** easily cross cell membranes (i.e. most sodium salts) and thus affects distribution of water between cells and ECF Plasma osmolality ***includes*** the osmotic contribution of ***urea*** (an ineffective osmole since it moves across the cell membrane and has little effect on water movement across the cell membrane). Ethanol is another osmole that enters cells rapidly and thus has no tonicity

Answer 10

1. _Obligate osmolar excretion_: Amount of osmoles which need to be removed by the kidney in order to maintain osmolar homeostasis. 2. Obligate osmolar excretion is dependent on the dietary intake a. *Basal metabolism (fasting) - approximately 7 mosmol/kg/day* 3. Normal individuals can dilute urine to 50 mosmol/L and concentrate to 1,000 mosmol/L 4. This allows a range of urine output of 7 ml/kg/day to 140 ml/kg/day a. This capacity allows us to accomplish both osmolar and water balance simultaneously

Answer 11

MAX dilute (50-75mOsmol/kg H20): **_1. Delivery of solute and water to diluting sites_** - fucked up in renal failure/ volume depletion **_2. Proper function of the diluting segment_** - Osmotic diuretics (no reabsorption in TAL)/ loop diuretics (block Na/K/2Cl) **_3. AVP/ADH must be absent for the collecting duct to be impermeable to water_** -needed to concentrate urine --\> duhhhhhhhh bitches

Answer 12

1. ***To retain significant free water*** (i.e. maximally concentrate the urine to 1000- 1200 mOsmol/Kg), the following are needed: a. **Development of a concentrated medullary interstitium by solute reabsorption in the TAL of the Loop of Henle** b. **Presence of AVP/ADH to stimulate insertion of AQP2 into the apical membranes of collecting duct cells** d. **Ability of collecting duct cells to respond to ADH/AVP by insertion of aquaporin channels**

Answer 13

Osmotic control: has a set point near normal value of serum osmolarity and is very sensitive to changes \> baseline non-osmotic: ineffective until intravascular volume \> 10% baseline --\> release AVP (overtakes osmotic control; activated V1A-R --\> raise BP; V2-R retain H20 --\> restore intravascular volume.

Answer 14

Results due to the presence of another effective osmole that causes free water to move from the intracellular compartment to the ECF resulting in cell dehydration. - Mannitol, glycine, marked hyperglycemia - txt: correcting the underlying condition (i.e. treatment of DKA) or removal of the osmotic agent

Answer 15

Results from a laboratory artifact due to marked hyperlipidemia or hyperproteinemia - Marked elevation in serum lipids or proteins causes a reduction in the fraction of serum that is water and results in an artificially low serum Na+ concentration - Laboratories that use ion-specific electrodes and direct potentiometry avoid the misdiagnosis of hyponatremia

Answer 16

True physiologic hyponatremia that results from excess water either due to AVP/ADH stimulation or impaired water excretion According to **AVP/ADH** levels 1. Circulating ADH levels are appropriately elevated 2. Circulating ADH levels are *inappropriately* elevated 3. Circulating ADH levels are appropriately suppressed According to the patients **volume status** 1. _Hypovolemic_ hypotonic hyponatremia 2. _Euvolemic_ hypotonic hyponatremia 3. _Hypervolemic_ hypotonic hyponatremia

Answer 17

formation of a cell- and protein-free plasma filtrate in the glomerulus.

Answer 18

movement (transport) of a substance out of the tubular lumen

Answer 19

Movement (transport) of a substance into the tubular lumen

Answer 20

Elmination of a substance from the body in the final urine

Answer 21

All blood flows thru GLOMERULI abdominal aorta --\> renal a. --\> interlobar a. --\> arcuate a. --\> interlobular a. --\> afferent arteriole --\> glomerulus --\> efferent arteriole --\> postglomerular capillary bed (vasa recta in medulla and peritubular capillaries in cortex) --\> venules --Interlobular v. --\> arcuate v. --\> interlobar v. --\> renal v.

Answer 22

1. essentially all blood flows thru glomeruli 2. inflow and outflow are arterioles (high resistance) 3. There are 2 capillary beds (filtration=glomerular capillaries); (absoprtion=postglomerular capillaries)

Answer 23

The formation of a nearly protein-free filtrate of plasma as blood passes through the glomerular capillaries - The glomerular ultrafiltrate has a composition identical to plasma _except_ for the almost complete absence of protein. - The ultrafiltrate is formed as fluid passes through the walls of the glomerular capillaries and into Bowman’s space to PCT

Answer 24

**Molecular Size**: Freely filtered=urea, glucose, inulin; ALBUMIN cannot pass (size and radius) **Electrical Charge**: Negative charges cannot pass more readily than neutral **Molecular Shape**: deformable structures can pass; globular=steric hindrance enothelial _fenestrations_, basal lamina, filtration slits (space b/w pedicels)

Answer 25

_electrostatic restriction_ plays a prominent role in limiting albumin transit across the filtration barrier **Most glomerular diseases compromise both the size- and charge-selective properties of the filtration barrier** **proteinuria =** glomerular injury

Answer 26

**Glomerulus:** Glomerular hydrostatic pressure is high, at about 50 mm Hg, and is constant throughout the glomerulus. Glomerular oncotic pressure increases throughout the length of the glomerulus, due to loss of plasma but retention of proteins (increased protein concentration; increased pull on water) Bowman's space hydrostatic pressure is about 15 mm Hg, and is constant. Bowman's space oncotic pressure is 0, because there is no protein content to pull water in. The net force is 10 mm Hg in favor of filtration. This is similar to non-renal capillaries, but the filtration coefficient is much higher in the kidneys due to greater surface area and hydraulic conductivity. The forces always favor filtration in the glomerulus; never absorption. **Post-glomerulus capillaries:** Capillary hydrostatic pressure is lower than in the glomerulus, due to the pressure drop that occurs at the efferent arteriole. The pressure is about 20 mm Hg. Capillary oncotic pressure begins at the same level as leaving the glomerulus since it relies on protein concentration. This number is high compared to systemic blood. As water is absorbed in the capillary bed, this pressure will fall. Interstitial hydrostatic pressure is low, at about 8 mm Hg. Interstitial oncotic pressure is also low, at about 6 mm Hg. The net movement is into the capillary, i.e. absorption, along the entire capillary bed.

Answer 27

Increasing afferent arteriolar resistance decreases the flow through the glomerulus (RBF). This reduces the hydrostatic pressure in the glomerulus and leads to a decrease in GFR. Decreasing afferent arteriolar resistance increases the flow through the glomerulus (RBF). This increases the hydrostatic pressure in the glomerulus and leads to an increase in GFR. Increasing efferent arteriolar resistance decreases the flow through the glomerulus (RBF), but it increases the hydrostatic pressure in the glomerulus, thus GFR increases. Decreasing efferent arteriolar resistance increases the flow through the glomerulus (RBF), but it decreases the hydrostatic pressure in the glomerulus, thus GFR decreases.

Answer 28

The formation of angiotensin II (a result of renin release from the juxtaglomerular apparatus) causes vasoconstriction at both the afferent and efferent arterioles; contraction of mesangial cells decreases the capillary filtration coefficient, Kf, which has an impact on the rate of filtration (fluid movement = Kf \* net filtration pressure). This _decreases RBF and GFR_. Other substances may dilate or constrict the afferent and efferent arterioles. For example, NO dilates the vessels, while norepinephrine constricts them. The afferent and efferent arterioles are innervated by the sympathetic nervous system. As the sympathetic nervous system activation is increased, norepinephrine is released, which acts on both vessels to cause constriction. This decreases RBF and GFR. During extreme activation of the sympathetic nervous system (i.e., shock), resistance in the afferent and efferent arteriole is so high that renal blood flow is severely reduced and GFR stops. The kidneys then do not receive oxygen and the cells die, leading to acute renal failure.

Answer 29

Autoregulation is the process by which the kidney controls and alters GFR and RBF in response to changes in blood pressure and flow, in order to maintain GFR within a narrow range (80–140 ml/min). **Myogenic**: ↑ mean arterial pressure → distend afferent arteriole → stretch afferent arteriolar vascular smooth muscle → smooth muscle cells contract → increase R_A (in the face of increased pressure) → **maintain constant RBF (and GFR)** **TGF**: ↑ GFR → ↑ flow thru tubule → ↑ flow past macula densa → Paracrine from macula densa to afferent arteriole → Afferent arteriole constricts → ↑ R_A→ LOW P_H in glomerulus → **LOW GFR**

Answer 30

PCT = 67% Loop of Henle = 25% DCT = 5% CD = \<3%

Answer 31

apical Na+ co-transporters (SGLT1/2, NaPi2) and Na+/H+ exchanger In the proximal tubule, Na+ moves across the apical membrane of the tubule down its concentration gradient, mostly via the Na+- glucose symporter. There is also the Na+/H+ antiporter, and a Na+-phosphate symporter (important during bone development). On the basolateral membrane, the Na+,K+-ATPase pumps Na+ into the interstitial space so it can be reabsorbed by the postglomerular capillaries. Water follows the movement of Na+, as does Cl-.

Answer 32

tDL, only water can move out of the tubule. The tDL is not permeable to Na+. In the TAL of the loop of Henle, the Na+,K+,2Cl- transporter (NKCC2) brings sodium, potassium, and chloride through the apical membrane; this is where most Na+ enters. The Na+,K+-ATPase in the basolateral membrane then pumps out Na+ into the interstitial space. The Na+/H+ exchanger also brings in some Na+ here. Called the *diluting segment*; uses a lot of energy to pump out Na+ on the basolateral side. Diuretics like ***furosemide*** and ***bumetanide*** block NKCC2, preventing sodium and water reabsorption. They also cause increased distal sodium reabsorption (with potassium loss), so are potassium wasting. They block the TGF mechanism, _preventing a decrease in GFR_. Loss of function mutations of NKCC2 causes **Bartter's syndrome**, with salt wasting, hypokalemia, alkalosis, and hypercalciuria.

Answer 33

Na+ is brought in by the Na+/Cl cotransporter through the apical membrane. Na+,K+-ATPase pumps Na+ into the interstitial space through the basolateral membrane. Cl- follows passively through the basolateral membrane. The NCC channel is sensitive to ***thiazide diuretics***. Prevents reabsorption of Na+ and water. These diuretics are potassium wasting as well, because the collecting duct will see more Na+ and water, and will compensate with more Na+ channels (ENaC). As a result, the Na+,K+-ATPase will have to increase its activity, bringing more K+ into the cell in the process, which has the opportunity to diffuse out into the duct via a K+ channel (thus wasting). Loss of function mutation causes ***Gitelman's syndrome***, with salt wasting, hypokalemia, alkalosis, and hypocalciuria.

Answer 34

ENaC (epithelial Na+ channel) brings sodium through the apical membrane. The Na+,K+-ATPase pumps Na+ through the basolateral membrane to the interstitial space where it can be reabsorbed by the postglomerular capillaries. ***Amiloride*** blocks the ENaC channel, causing more Na+ and water excretion. This diuretic is potassium sparing, since the collecting duct will not have the opportunity to detect and upregulate the ENaC channel in a way that will affect potassium excretion significantly. The ENaC is located in principal cells and are sensitive to aldosterone; in response to binding of aldosterone to the aldosterone receptor, the ENaC channel will be produced and shuttled to the apical surface and to allow reabsorption of Na+. In ***Liddle's syndrome***, a mutation causes the channel to always be open. This leads to salt retention and severe hypertension. In ***Pseudohypoaldosteronism***, a mutation causes loss of function of the channel. This leads to salt wasting, hyperkalemia, acidosis, and hypotension.

Answer 35

In early PCT, glucose is reabsorbed by SGLT2 (Na+, glucose cotransporter; high capacity, low affinity, \*98% glucose reabsorbed) --\> Basolateral GLUT2 --\> diffusion to intersitial space In the late PCT, the apical SGLT1 (2Na+, glucose cotransporter; low capacity, high affinity for glucose --\> Basolateral GLUT1 channels facilitate diffusion to the interstitial space.

Answer 36

Organic -: Phenol red; PAH (diagnostic agent measuring RPF); Penicillin; Furosemide; Acetazollamide; Creatinine Organic +: Histamine; Cimetidine; Cisplatin; NE; Quinine; Tetraethylammonium; Creatinine

Answer 37

fenestrated endothelium of the glomerulus and the podocyte processes that wrap around the capillaries. secreted by podocytes\*

Answer 38

Transitional epithelium

Answer 39

acts as a funnel that combines all the major calyces and narrows the tube to connect to the ureter

Answer 40

part of the urinary tract that collects urine from the medullary pyramid and delivers it to the ureter

Answer 41

where the renal pelvis joins to the ureter; there is a narrowing at this junction. (Constriction point)

Answer 42

where the ureter connects the bladder; there is narrowing at this junction. (constriction point)

Answer 43

- change in surface area - Humoral agents (Angiotensin II) decrease SA for filatration via ctrx of mesangial cells

Answer 44

NaCl (NKCC2) increased [NaCl] (NKCC2) --\> release of signaling molecules (Ca, ATP, Adenosine) from macula densa --\> CTRX *afferent arteriole* --\> LOW GFR Tubuloglomerular Feedback

Answer 45

PCT (AQP1)

Answer 46

establishing medullary interstitial osmotic gradient Countercurrent flow Different water permeability of adjacent structures (descending/ascending limb) Energy (Na,K-ATPase) "loop diuretics" - Furosemide; Bumetanide

Answer 47

PCT 300mOsm/L

Answer 48

countercurrent blood flow (*vasa recta*) *passive* Solute diffuses from the ascending vasa recta into the descending vasa recta. This process “traps” solute in the inner medulla. ADH decreases medullary blood flow --\> Enhancing concentration gradient

Answer 49

Increase=the urine cannot be as concentrated and the flow increases Decrease=increasing interstitial osmolarity and increasing ability of the countercurrent multiplier to remove water from the urine

Answer 50

increase in plasma osmolality detected in supraoptic and paraventricular neurons of the *hypothalamus* *Right Atrium* baroreceptors for large decreases \>10% Collecting Duct and Vasoconstriction of Vasa Recta

Answer 51

Constrict renal arteriole --\> Decrease GFR (decreases filtered load of Na+ --\> Increases PCT Na+ reabsorption (Na+/H+ exchanger) ANGII --\> Aldosterone --\> High Na+ reabsorption in CD ANGII vasoconstriction --\> Increased TPR Stimulates thirst reflex; ADH release; Decreased medullary blood flow

Answer 52

Increased ANGII --\> Aldosterone --\> Increased Na+ reabsorption by CD (ENaC \*Amilioride) Triggered by increased AngII, Decreased plasma Na+, Increased plasma K+

Answer 53

Activated by SNS Increased Na+ reabsorption by PCT (Na+/H+ exchanger)

Answer 54

Atrial stretch (increased ECF) Decrease Na+ reabsorption in CD (Inhibits ENaC)

Answer 55

Increased ECF volume Decrease Na+ reabsorption by _all nephron segments_ Direct effect to inhibit the basolateral Na,K-ATPase

Answer 56

*Glomerulo-tubular Balance* PCT reabsorbs a constant fraction of filtered Na+ (67% of filtered load) Mechanism: ↑ GFR --\> ↑ oncotic pressure of plasma entering the peritubular capillaries --\> ↑ reabsorption (Starling forces). *Tubuloglomerular Feedback* ↑ GFR --\> ↑ solute and water delivery to the macula densa --\> TGF-mediated afferent arteriolar constriction --\> ↓ GFR back toward normal.

Answer 57

↓ plasma oncotic pressure --\> Starling forces --\> ↑ GFR ( ↑ ECF volume dilutes plasma proteins) ↑ arterial pressure --\> ↑ capillary hydrostatic pressure in the glomeruli (autoregulation is not perfect) --\> ↑ GFR ↓ AngII levels --\> ↓ renal arteriolar resistance --\> ↑ RBF & GFR ( ↑ ECF volume --\> ↓ renin release) ↓ sympathetic tone & circulating catecholamines --\> ↓ renal arteriolar resistance --\> ↑ RBF and GFR ( ↑ arterial pressure sensed by carotid & aortic baroreceptors)

Answer 58

↓ AngII levels --\> ↓ Na+ reabsorption in proximal tubule ↓ aldosterone levels --\> ↓ Na+ reabsorption in collecting duct ( ↓ AngII levels --\> ↓ aldosterone release) ↓ sympathetic tone & circulating catecholamines --\> ↓ Na+ reabsorption in proximal tubule ↑ ANP levels --\> ↓ Na+ reabsorption in collecting duct ( ↑ blood volume sensed by atrial stretch receptors) ↑ endogenous digitalis-like substance (unknown stimulus) --\> generalized ↓ in Na+ reabsorption

Answer 59

140 mEq/L inside the cell A bump in potassium intake will quickly be shuttled into the cells; over time the extra potassium will be excreted in urine.

Answer 60

PCT=80% (follows H2O paracellularly) Loop of Henle=10% (TAL NKCC2)

Answer 61

α-Intercalated cells (ICT, CCT & MCD): active reabsorption (during low dietary K+ intake) \*Apical uptake via *H+-K+-ATPase* --\> ↑intracellular [K+] --\> exits cell via basolateral K+ channel Principal cells (ICT and CCT): active secretion \*K+ uptake from peritubular interstitium via basolateral Na+-K+-ATPase --\> ↑ intracellular [K+] --\> passive flux of K+ across apical membrane (probably via a K+ channel)

Answer 62

↑ Dietary K+ intake --\> ↑ [K+]_ECF --\> increase Na+-K+-ATPase activity --\> ↑ K+ uptake across basolateral membrane of distal tubule & collecting duct cells --\> ↑ K+ secretion --\> ↑ K+ excretion. ↑ P_K --\> direct stimulus of aldosterone release (adrenal cortex) --\> ↑ apical Na+ entry into CD cells --\> ↑ lumen negativity and Na+- K+-ATPase activity --\> ↑ K+ secretion --\> ↑ K+ excretion.

Answer 63

Furosemide Mannitol Where do they work??

Answer 64

Amiloride Spironolactone Where do they act?

Answer 65

Intravascular = 1/4 of the ECF Interstitial = 3/4 of the ECF

Answer 66

When glucose is markedly elevated (uncontrolled DM) or in reduced renal function (elevated urea)

Answer 67

Amount of osmoles which need to be removed by the kidney in order to maintain osmolar homeostasis \*Obligate osmolar excretion is dependent on the dietary intake *Basal metabolism (fasting) - approximately 7 mosmol/kg/day*

Answer 68

1. **Delivery of solute and water to diluting sites** - renal failure (low GFR) --\> low solute delivery - volume depletion or effective intravascular volume depletion (CHF, cirrhosis, nephrotic syndrome), PCT has higher Na+/H2O delivery --\> low solute delivery 2. **Proper function of the diluting segment** - osmotic diuretics (mannitol) - loop diuretics 3. **AVP/ADH must be absent for the collecting duct to be impermeable to water**

Answer 69

**To retain significant free water** * Development of a concentrated medullary interstitium by solute reabsorption in the TAL of loop of henle* * Presence of AVP/ADH --\> AQP2 in collecting duct* * Abilitiy of collecting duct to respond to AVP/ADH by insertion of AQP2*

Answer 70

intravascular volume depletion (\>10%) \*life-saving thru V1/V2R --\> raise BP/retain H20/restore intravascular volume vs. sensitive to any changes above baseline serum osmolarity

Answer 71

(is a marker not a cause) usually due to nonosmotic release of AVP

Answer 72

1. The brain is most susceptible to the sudden decrease in serum Na+ because it is confined within the rigid skull 2. Acute hyponatremia causes nausea, vomiting, and confusion due to brain edema 3. Severe brain edema leads to seizures, even herniation and death 4. When hyponatremia develops slowly (over several days), the brain cells can adapt by releasing intracellular K+ and Cl- initially; and subsequently, organic osmolytes (myoinositol, amino acids) such that the cell volume is reduced to near normal levels 5. This is the reason why chronic hyponatremia is frequently asymptomatic unless the serum Na+ is very low (i.e. \<120 mEq/L)

Answer 73

Hypertonic hyponatremia from presence of another effective osmole that causes free water to move from the ICF --\> ECF --\> cell dehydration \*Mannitol, glycine, High [glucose] rx: correct the underlying condition

Answer 74

Isotonic or "Pseudohyponatremia" results from a laboratory artifact due to marker hyperlipidemia or hyperprotenemia --\> reduced fraction of serum that is water --\> artifically low serum [Na+] \*labs that use ion-specific electrodes avoid this misdiagnosis

Answer 75

Hypotonic hyponatremia results from excess water from either AVP/ADH or imparied water excretion 1. AVP/ADH 2. Volume status

Answer 76

True volume depletion (low ECF volume) --\> loss of fluid volume (Na+) --\> stimulate ADH secretion --\> attempt to restore ECF \*volume depleted (hypotension, flat neck veins, orthostatic) * GI losses; blood losses; excessive sweating, burns* --\> **Urine Na+ \< 20 mEqL** (max reabsorption at PCT) * Renal Na+ losses* (diuretics, adrenal insufficiency, salt-wasting nephropathies) --\> **Urine Na+ \> 20 mEqL**

Answer 77

Primary water gain (normal ECF) --\> excess ADH (inappropriate), excessive water intake (psychogenic polydipsia), reduced solute intake (beer-drinkers), hypothyroidism appear euvolemic on exam

Answer 78

**ECF volume excess w/ intravascular volume depletion** (low effective circulating volume) 1. heart failure, cirrhosis, nephrotic syndrome 2. ADH is inappropriately activated due to low circulating volume 3. Urine Osm is **high** due to ADH activity; **Urine Na+ \<20 mEq/L** --\> max reabsorption at PCT/renin from intravascular volume depletion **\*Advanced renal failure** **--\>** high Urea --\> high measured plasma osmolality --\> dilutional hyponatremia

Answer 79

1. In *chronic hyponatremia*, the Na+ correction should **never exceed \>10 mEq/L in 24 hours** to avoid **osmotic demyelination syndrome** 2. If symptomatic with life-threatening seizures, then raising the serum Na+ by ~ 4-6 mEq/L acutely with **3% hypertonic saline** is appropriate 3. Correction of the intravascular volume with **0.9% normal saline** is appropriate for **hypovolemic hyponatremia** (caution to avoid correcting too quickly; once volume is repleted, the stimulus for ADH will be suppressed and patients can have a brisk water diuresis increasing the serum Na+ quickly) 4. Correction of the underlying cause (treatment of hypothyroidism, increasing solute intake for tea and toasters) 5. **SIADH** – correct the underlying cause if identifiable otherwise free water restriction (generally to 1200 ml per day), increase solute intake (if unable to eat enough protein then salt tablets may be added), and can add loop diuretics in efforts to limit the addition of NaCl to the medullary interstitium which is needed in order to maximally concentrate the urine in the presence of ADH • V2 receptor antagonists (Conivaptan and Tolvaptan are now available but are costly and are not indicated for long-term use 6. **Hypervolemic hyponatremia** (edematous states) are typically treated with diuretics and fluid restriction

Answer 80

area in brain that are slowest in reaccumulating osmolytes after rapid correction --\> massive axonal demyelination in **pontine white matter** secondary to osmotic changes (chronic hypnatremia) acute parallysis, dysarthria, dysphagia, diplopia, loss of consciousness. Can cause “locked-in syndrome.” **correcting serum Na+ too fast**"from low to high your pons will die" "from high to low your brain will blow" (cerebral edema/herniation)

Answer 81

1. duration of hyponatremia (\>2 days) 2. correction of Na+ \>10 mEq/L within 24h 3. low serum Na+ (\<120; \<105 mEq/L increasing risk)

Answer 82

hypernatremia primarily occurs in patients who _cannot express thirst normally_ (i.e. elderly, infants) OR who do _not have access to free water_ (hospitalized patients in the intensive care unit)

Answer 83

Loss of free water only is referred to as dehydration Loss of both Na+ and water is referred to as hypovolemia

Answer 84

**Central DI** – due to insufficient release of ADH in response to an increased serum Na+ or osmolarity (can be partial or complete impairment of ADH). -Due to lesions of the hypothalamic osmoreceptors, supraoptic/paraventricular nuclei, or superior portion of the supraoptichypophyseal tract due to trauma, surgery, or tumors **Nephrogenic DI** (can be partial or complete)– reduced action of ADH at the collecting tubule due to either mutations in the V2R or AQP2 or medications (i.e. lithium).

Answer 85

In chronic hypernatremia (\>48h duration), the serum Na+ correction **should not exceed \>10 mEq/L over 24h** in efforts to avoid cerebral edema (rapid lowering once cerebral adaptation has occurred causes additional osmotic water movement into brain cells resulting in cerebral edema, encephalopathy, seizure, and permanent neurologic damage) In both hyponatremia and hypernatremia, the serum Na+ must be followed closely (i.e. checked every 2-4 hours) and therapy should be modified accordingly to AVOID too rapid of correction

Answer 86

1. **K+ intake through the diet** 2. **GI losses**: GI tract secretes 5-10% of absorbed K+ daily 3. **Renal losses**: 90-95% is regulated by the kidney 4. **Transcellular K+ shift**: Overall K+ stores remain the same but can redistribute between the ICF and ECF based on transcellular shift

Answer 87

10-25% is reabsorbed in the TAL of Henle driven by NKCC2 *active process* driven by basolateral Na,K-ATPase K+ is recycled across _luminal membrane_, allowing continued activation of NKCC2 Activity of luminal K+ channel is *inhibited by ATP* allowing a ling to level of Na+ reabsorption 1. As more Na+ enters cell, Na+ will be transported out of the cell into the peritubular capillary by *Na+-K+ ATPase --\> lowering cellular ATP* level and stimulates activity of luminal K+ channel 2. Permits return of reabsorbed K into lumen and further Na+ absorption

Answer 88

K+ actively transported into cell by Na+-K+ ATPase at basolateral membrane • Secreted into tubular fluid (TF) down a favorable electrochemical gradient via luminal K+ channels (ROMK) Governed by factors that affect passive transport Concentration gradient across luminal membrane – High intracellular [K+] and low TF [K+] Electrical gradient generated by reabsorption of Na+ via luminal Na+ channels (ENaC) K+ permeability of luminal membrane – # of open K+ channels

Answer 89

**Aldosterone** – augments K+ secretion in principal cells – Increase # open Na+ and K+ channels in luminal membrane – Enhances activity of Na+-K+ ATPase pump **Plasma [K+]** – Increase # open Na+ and K+ channels in luminal membrane – Enhances activity of Na+-K+ ATPase pump **Distal flow rate** – Increase in distal flow rate washes secreted K+ away and replaces with relatively K+ free fluid --\> favorable [K+] gradient for secretion into TF – When distal flow rate reduced, high luminal [K+] (due to less washout of secreted K+) and low urine flow --\> reduction in absolute rate of K+ secretion (additionally voltage gated channels – Maxi K – stimulated by flow) **Distal Na+ delivery** – Entry of Na+ via Na+ channel (ENaC) makes lumen electronegative – Transport of Na+ into peritubular capillary by ATPase pumps more K+ into cell – More K+ secreted into electronegative lumen

Answer 90

Insulin and Beta-2 agonist increase Na,K-ATPase Alkalosis: H+ will leave cell in order to minimize extracellular pH (to maintain electoneutrality, K+ will enter the cell; small effect) Hypokalemic period paralysis: Characterized by acute attacks in which sudden movement of K+ into cells lowers the plasma K+ to 1.5-2.5 mEq/L Precipitated by rest after exercise, stress, or a carbohydrate meal (events associated with release of epinephrine or insulin) a. Familial – autosomal dominant associated with mutations in dihydropyridine calcium channel in skeletal muscle b. Acquired – thyrotoxicosis (predominantly young Asian males)

Answer 91

**Vomiting and nasogastric tube output** 1. Associated with metabolic alkalosis due to HCl acid loss 2. K+ loss from emesis ~ 5-10 mEq/L 3. *Concurrent urinary losses* due to activation of aldosterone and an increase in plasma bicarbonate that increases the filtered bicarbonate above its reabsorptive threshold. Because Na+ pairs with bicarbonate in the tubular fluid, the increase in distal delivery of Na+ will further promote K+ loss – net effect is profound hypokalemia **Diarrhea and laxatives** 1. Associated with metabolic acidosis due to bicarbonate losses 2. K+ loss from stool can range from 20-50 mEq/L

Answer 92

**I. Conditions associated with metabolic alkalosis** 1. Diuretics (loops and thiazides) 2. Salt wasting nephropathies (associated with hypotension) a. *Bartter’s syndrome*: (\*think loop diuretic) --\> Defect in NaCl reabsorption in TAL of Loop of Henle (any transporter) * Gitelman’s syndrome* (\*think thiazide diuretic) Defect in the gene encoding the thiazide-sensitive NaCl cotransporter in the distal convoluted tubule \*Low urinary calcium distinguishes Gitelman’s from Bartter’s 3. Mineralocortecoid excess (associated with hypertension) * Liddle’s syndrome*: gain of function mutation in the epithelial Na+ channel (ENaC) located on the luminal side of the principal cell **II. Conditions associated w/ metabolic acidosis** -renal tubular acidosis/nonreabsorbable anion **III. Magnesium** Hypokalemia occurs in 40-60% of cases of hypomagnesemia 2. Often due to underlying disorders that waste both magnesium and K+ (i.e. diarrhea, diuretics)

Answer 93

**Cardiac arrhythmias and ECG abnormalities** 1. Premature atrial and ventricular beats, sinus bradycardia, AV block, and ventricular tachycardia/fibrillation 2. Decrease in amplitude of T wave and increase in amplitude of U wave (occur at end of T wave – seen in lateral precordial leads V3-V6) **Muscular** weakness and muscle cramps (hyperpolarize skm cells impair ctrx) impair NO release --\> predispose to rhabdomyolysis during vigorous exercise **Hormonal** impairs insulin release and end-organ sensitivity to insulin **Renal** tubulointerstitial and cystic changes in the parenchyma of the kindey (prolonged hypokalemia) polyuria (impairs concentrating ability) hypertension (increased renal vascular resistance)

Answer 94

Urinary K+ to creatinine ratio: \< 15 mEq/g (assuming most people excrete 1000mg of creatinine in urine) suggests appropriate conservation of K+ and extrarenal cause (GI, transcellular shift)

Answer 95

low= stool losses high= RTA, nonreabsorbable anion

Answer 96

low= vomiting, remote use of diuretics high= check BP and volume status low bp/volume= Diuretics, salt wasting nephropathies, ongoing vomiting with sustained metabolic alkalosis high bp/volume= mineralocorticoid excess \***always check magnesium** - hypokalemia due to magnesium wasting cannot be corrected until magnesium is corrected

Answer 97

Elevation in measured serum K+ is due to K+ _movement out of the cells_ *during* or *after* a blood specimen has been drawn 1. Hemolysis (destruction of red blood cells) due to technique (clenching, prolonged tourniquet, venipuncture trauma) during blood draw 2. Thrombocytosis 3. Leukocytosis (acute leukemia)

Answer 98

**_Metabolic acidosis_**: H+ will enter the cell in order to buffer the extracellular pH (primarily inorganic acids) 1. In order to maintain electroneutrality, K+ will leave the cell (overall a small effect) **_Hyperglycemia and hyperosmolality_** 1. Elevation in serum osmolality results in water movement from the ICF to the ECF a. Results in increased [K+] in the cell – K+ will move out of the cell down concentration gradient b. Solvent drag from water movement **_Nonselective β-antagonists_**: Interfere with K+ uptake into the cell by β- adrenergic receptors **_Exercise_**: K+ released by muscle cells (causes local vasodilatation for increased blood flow) **_Tissue breakdown_**: Rhabdomyolysis (muscle breakdown), lysis of large tumor burden after chemotherapy, burns cause release of K+ into the ECF **_Digitalis (Digoxin) toxicity_**: Inhibits the Na+/K+ ATPase pump vii. **_Hyperkalemic familial periodic paralysis_**: 1. Autosomal dominant due to point mutation skeletal muscle Na+ channel 2. Precipitated by cold, rest after fasting, and small amounts of K+ ingestion

Answer 99

1. Able to maintain near normal levels of K+ as long as distal flow rate and aldosterone secretion is maintained 2. Hyperkalemia develops in patients who are oliguric (decreased distal flow rate) who have an additional problem a. Excess K+ load, aldosterone blockade (ACE inhibitors, angiotensin receptor blockers, and alodosterone blockers)

Answer 100

1. Hypovolemia 2. Effective arterial volume depletion with extracellular volume excess a. Heart failure b. Cirrhosis of the liver

Answer 101

1. **Mineralocorticoid deficiency** - Primary adrenal insufficiency (adrenal gland does not generate aldosterone in response to renin) - Hyporeninemic hypoaldosteronism (diabetic – Type IV RTA) – low plasma renin levels and aldosterone levels) 2. **Tubulointerstitial disease** a. Sickle cell disease and urinary tract obstruction i. Impaired Na+ reabsorption in the principal cell reducing K+ and H+ secretion (also called Type I distal hyperkalemic RTA) 3. **Drugs** - ACEi, ARB, spironolactone --\> decrease renin release - Nonsteroidal anti-inflammatory drugs (NSAIDs) and beta blockers

Answer 102

a. Severe muscle weakness or paralysis i. Ascending weakness that begins with the legs and progresses to trunk and arms --\> flaccid paralysis b. Cardiac arrhythmias and ECG abnormalities i. Bundle branch block, advanced AV block, sinus bradycardia, sinus arrest, slow idioventricular rhythm, ventricular tachycardia and fibrillation, asystole ii. ECG 1. Early - tall peaked T waves and shortening of the QT interval 2. More advanced - prolongation of PR and QRS interval (may lose P wave altogether with widened QRS sine wave)

Answer 103

may help distinguish **functional hypoaldosteronism** from other disorders (volume depletion) i. Gradient between the tubular fluid and plasma K+ - estimates aldosterone activity by measuring the K+ concentration in the tubular fluid at the end of the cortical collecting tubule (site responsible for K+ secretion) ii. [Urine K ÷ (Urine osmolality / Plasma osmolality)] ÷ Plasma K iii. Value \< 5 is suggestive of **hypoaldosteronism**

Answer 104

a. **_Antagonizing membrane effects of K+ with calcium_** (reserved for patient’s with ECG changes, acute rises in serum K+) i. _Calcium Choloride_ b. **_Driving extracellular K+ into cells_** i. _Insulin administered with glucose_ ii. _β-2 agonist (albuterol)_ **c. _K+ removal_** _Diuretics_ _Cation exchange resins_ _Dialysis_ _*\*treatment of reversible causes*_

Answer 105

Bowman's capsule Tubular system: PCT, Loop of Henle, DCT

Answer 106

Collecting tubules Major/Minor Calyces Renal Pelvis Ureters

Answer 107

**WT1 transcription factor** Null mutation results in renal agenesis. Mutation results in Wilm’s Tumor (kidney cancer) = Wilm’s tumor suppressor gene 1= WT1. WAGR associated w/ deletion of WT1 Denys-Drash associated w/ *mutations* of WT1 **PAX-2 transcription factor** Mutations result in malformations like coloboma (and small kidneys)

Answer 108

P – **Pulmonary hypoplasia** (urine/amniotic fluid is needed for lung development) O – **Oligohydramnios** (insufficient amniotic fluid = trigger) T – **Twisted face** (compressed features due to oligohydramnios) T – **Twisted skin** (ditto) E – **Extremity defects** (ditto) R – **Renal failure in utero** (primary cause)

Answer 109

Ureteric bud fails to induce differentiation of metanephric mesenchyme --\> nonfunctional kidney consisting of cysts and connective tissue. Predominantly nonhereditary and usually unilateral; bilateral leads to Potter sequence.

Answer 110

Inferior poles of both kidneys fuse abnormally. As they ascend from pelvis during fetal development, horseshoe kidneys get trapped under *inferior mesenteric artery* and remain low in the abdomen. Kidneys function normally. Associated with *hydronephrosis* (eg, ureteropelvic junction obstruction), renal stones, infection, chromosomal aneuploidy syndromes (eg, Turner syndrome; trisomies 13, 18, 21)

Answer 111

Acts primarily on the PCT cells to inhibit bicarbonate absorption. Thus prevents disposal of carbonic acid, slowing the reaction that uses H+ ions, and slowing the Na+/H+ antiporter, thus preventing reabsorption of sodium. They are poor diuretics, however, because the rest of the tubule adapts to reabsorb more sodium. chemically related to *sulfonamide antimicrobial agents*

Answer 112

inhibit the NKCC2 in the TAL of the loop of Henle by binding to the Cl^- binding site --\> High excretion of Na⁺ and Cl^- w/ an associated increase in Ca²⁺ and Mg²⁺ (loss of transepithelial electropoetential difference - normally drives reabsorption adverse effects: Higher Na+ delivery to distal tubules enhances K⁺ and H⁺ excretion, part RAAS. Volume depeletion, Hyperuricemia --\> gout; develop in 1st 2-4 wks of therapy *_Ototoxicity w/ NKCC2 isoform in cochlea_*

Answer 113

hydrochlorothiazide and _chlorthalidone_ (longer acting; 2x more potent) inhibit the Na/Cl symport in the DCT chronic use associated w/ a decrease in Ca²⁺ excretion (reduce kidney stones) Thiazide use associated w/ hyperglycemia when creatinine clearance has fallen to 40-50 mL/min, thiazides efficacy is diminished, due to reduced Na+ delivery to DCT \*Thiazides usually used in the Hypertension, nephrogenic DI

Answer 114

Ameloride and Triamterene Na+ normally reabsorbed via ENaC w/o an anion, creating a lumen negative electrical gradient --\> K+/H+ secretion drugs may be used w/ CA inhibitors, loop diuretics, thiazides side effects make sense: hyperkalemia and metabolic acidosis hyperkalemia caused by: * renal failure* * K+-sparing diuretics* * ACEi or angII blockers* * NSAIDs* * dietary K+ supplements*

Answer 115

**Spironolactone** - competitively inhibit the binding of aldosterone to the MR (higher [aldosterone] --\> higher effect of MR antagonists) aldosterone binding to mineralcorticoid receptor leads to angiotensin-induced proteins (NaCl transport enhanced, the lumen-negative transepithelial voltage is increased, upregulated kinase to inhibit degradation of Na+ channels (more Na+ reabsorb) SE: Hyperkalemia; Gynecomastia in men; loss of libido in women \*used w/ thiazide or loop diuretic in txt of hypertension and edema; dual therapy to limit hyperkalemia, enhance diuresis; reduces morbidity and death when used w/ heart failure therapy.

Answer 116

Acute decompensated heart failure Chronic stable heart failure Cirrhosis with ascites Nephrotic syndrome Chronic kidney disease

Answer 117

The thiazides and thiazide- type diuretics are important antihypertensive drugs. Not all generalized edema requires treatment with diuretics. When the drugs are used in non-emergent situations it is most often prudent to induce slow change rather than rapid change. Pulmonary edema is the only life-threatening edema state.

Answer 118

Angiotensin II, aldosterone and norepinephrine produced by diuretic-induced neurohumoral activation can all foster tubular Na⁺ reabsorption. However pharmacologic blockade of these pathways does not prevent secondary Na⁺ retention in the post-diuretic phase, i.e., when diuretic action is nil. Now, new steady state and ECF is LOWER, but the diuretic-induced Na+ losses are offset by: _Neurohumorally-mediated increases in tubular Na⁺ reabsorption at sites that are not influenced by the diuretic_ _Increased distal delivery of Na⁺ increases distal Na⁺ reabsorption. Furosemide administration leads to distal tubular hypertrophy and increased Na-K ATPase expression_

Answer 119

* Abrupt loss of kidney function * Retention of urea and other nitrogenous waste products * Dysregulation of extracellular volume and electrolytes

Answer 120

Breakdown product of creatinine phosphate in muscle * Filtered by the kidney and used to estimate kidney function/filtration * _Inversely proportional to function_ * Higher the creatinine, the lower the filtration

Answer 121

Urea nitrogen formed from protein catabolism by the liver * Filtered by the kidney and used as an additional measure of kidney function * High BUN generally reflects lower filtration * *Caveat: BUN can increase independent of kidney function* *–Steroids, tetracycline antibiotics, or reabsorption of blood in GI tract*

Answer 122

divides kidney injury into 3 stages based on absolute and change in serum creatinine and reduction in urine output. \*The higher the stage, the worse the outcome.

Answer 123

Based on serum creatinine and urine output (imperfect biomarkers) By the time serum creatinine rises or urine output decreases, substantial injury may have already taken place (typically in the preceding 24-48h before serum creatinine

Answer 124

True volume depletion (loss of Na+ from ECF) GI losses, hemorrhagic shock, renal losses, cutaneous losses Total ECF may be increased but arterial blood volume perceived by baroreceptors in the carotid sinus and glomerular afferent arterioles is low --\> **edematous states** **-Hepatic failure, Hepatic cirrhosis, Sepsis** *decreased* renal perfusion --\> afferent arteriole vasodilation --\> efferent arteriole constriction --\>Increased *filtration fraction* --\>higher oncotic pressure in post-glomerular capillaries --\>Increase salt/water reabsorption in PCT Activation of angiotensis II and ADH lead to increased salt and water reabsorption (NSAIDs) block prostaglandin (blocks afferent arteriolar dilatation) and ACE inhibitors/Angiotensin receptor blockers (block efferent \>afferent arteriolar constriction) prevent proper homeostasis

Answer 125

–Vomiting, diarrhea, GI bleeding –Heart failure, liver disease/cirrhosis, sepsis PE: Orthostatic hypotension, skin tenting, dry mucous membranes –Elevated jugular venous pressure with hypotension (heart failure), edema with hypotension **BUN:creatinine ratio \>20:1** **FENa: \<1% (fraction of filtered sodium excreted in the urine)** **Urine will have no protein, blood, or white blood cells; high specific gravity; no casts**

Answer 126

BUN:creatinine ratio \>20:1 FENa: \<1% (fraction of filtered sodium excreted in the urine) Urine will have no protein, blood, or white blood cells; high specific gravity; no casts

Answer 127

mesures the *percent of filtered Na+* excreted in the urine Used to differentiate b/w *prerenal disease* and acute *tubular necrosis* •FENa is \<1% in prerenal disease and indicates that the patient will be responsive to volume (i.e. IV fluids)

Answer 128

Patch necrosis of PCT and TAL --\> cannot sufficiently reabsorb Na+ and Cl- --\> More salt delivered to distal nephron --\> macula densa senses this increase in Cl- and activates tubuloglomerular feedback, causing constriction of the afferent arteriole to reduce renal blood flow and glomerular filtration rate. Lowering of GFR limits salt wasting and volume depletion and is a critical mechanism to prevent death in patients with ATN.

Answer 129

**Ischemic**, such as occurs with prolonged volume depletion, low blood pressure, or sepsis **Toxin-related**, and can occur from radiocontrast media (patients who are at risk include those with underlying kidney disease, diabetes mellitus, or hypotension), drugs (aminoglycosides, amphotericin B, cisplatin), or heme pigments (result of rhabdomyolysis)

Answer 130

**Pre-renal disease** Low sodium and chloride concentration, \<10 mEq/L BUN:creatinine ratio \>20:1 FENa: \<1% (fraction of filtered sodium excreted in the urine) Urine will have no protein, blood, or white blood cells; *high specific gravity*; no casts **ATN** Urinary Na+ and Cl- concentration will be higher than pre-renal disease, due to dysfunction of the tubules. \>20 mEq/L BUN:creatinine is 10–15:1. Due to tubular dysfunction, not as much urea is reabsorbed into the blood, so the serum concentration will be lower than in pre-renal disease FENa \> 2%. More Na+ is excreted in the urine due to tubular dysfunction as compared to pre-renal disease in which the tubules are functioning normally. Specific gravity of urine will be close to 1, due to loss of concentrating ability. Low grade proteinuria due to impaired protein reabsorption in the proximal tubule Urinary sedimentation has *“muddy” brown casts*; tubular cells

Answer 131

History of drug exposure (NSAIDs, penicillins, cephalosporins, sulfonamides, rifampin, proton pump inhibitors, ciprofloxacin), autoiummine disease (Sjogren's syndrome, sarcoidosis) or infection (Legionella, leptospira, cytomegalovirus) For drug-induced, onset is 3–5 days after second exposure; weeks to months after first exposure (type IV hypersensitivity reaction)

Answer 132

Physical exam, see triad of rash, fever, and eosinophilia. Full triad only observed ~10% of the time, with fever and eosinophilia most common. This applies to drug-induced cases. For Sjogren's syndrome, see dry eyes, mouth **Labs** **Acute rise in serum creatinine** that corresponds to drug administration **Peripheral eosinophilia** on drug smear **Eosinophils in the urine** (\>1%); not sensitive or specific Variable proteinuria **WBCs, may see WBC casts** in the sedimentation A biopsy is diagnostic

Answer 133

Cast nephropathy: seen in multiple myeloma. Excess production of immunoglobulin light chains must be filtered into the urine and can obstruct the tubules. **Tumor lysis syndrome**: after chemotherapy treatment, breakdown of large tumor causes release of uric acid and phosphate that can precipitate and block tubules. Phosphorous-containing enemas: acute calcium phosphate deposition in the tubules, inflammation Medications: acyclovir, sulfonamide antibiotics, methotrexate All primarily consist of **precipitation of a substance in the tubules** in the setting of volume depletion and acidic urine.

Answer 134

History of aortic manipulation or coronary/renal angiography (2–8 weeks); history of atherosclerotic disease. Causes inflammation, cholesterol emboli (ischemic injury) On physical exam, livedo reticularis rash. Laboratory evaluation, see low serum complement, peripheral eosinophilia. Bland sediment in urinalysis. In cholesterol emboli, the **rise in serum creatinine is subacute, and occurs 2–8 weeks** after the procedure. In **radiocontrast exposure, serum creatinine will rise within 72 hours**.

Answer 135

**Calculus** (stone) in a solitary kidney, at the ureteropelvic junction; bilateral staghorn calculi Anatomic abnormalities (most commonly seen in children), including ureteral strictures, stenosis, or abnormalities in ureteral valves that cause an obstruction **Benign prostatic hyperplasia** (most common in men \>50 years) Urethral stricture Malignancies (extra-urinary) that compress the ureters bilaterally

Answer 136

Take a good history Were there episodes of prolonged hypotension? (septic shock) Drug, nephrotoxin exposure: did the patient use NSAIDs, sulfonamides, contrast, enemas, aminoglycosides Good physical exam: determine the patient's volume status (hypovolemic or reduced effective vascular volume points to pre-renal cause); look for rash Utrasound, to rule out obstruction Lab values: urinalysis. Look at Na+, FENa, sedimentation, proteinuria, hematuria, crystals. Some cases warrant renal biopsy.

Answer 137

**Uremia**: Symptoms from high levels of wastes in the serum. Nausea, vomiting, anorexia, dysguria (food tastes metallic), altered mental status, pericarditis Electrolyte abnormalities Hyperkalemia (due to decreased distal flow) Hypokalemia (due to increased distal flow) (aminoglycosides) Metabolic acidosis Extracellular volume excess Chronic kidney disease Due to unresolved or recurrent AKI

Answer 138

**Volume resuscitate** with saline or colloid (blood) if needed Ensure renal artery perfusion during shock (use vasopressor or ionotropes) Treat underlying infection if septic Prevent further injury by avoiding NSAIDs, and giving sufficient water with medications known to precipitate (acyclovir) Pretreat with sodium bicarbonate and N-acetylcysteine before giving radiocontrast agent (prevent injury) If patient has AIN, remove offending drug; steroid if patient does not improve Renal replacement therapy is indicated in patients who have refractory acidemia, volume overload (pulmonary edema), hyperkalemia, or uremia

Answer 139

Young age of onset (before third decade) Sudden onset Refractory or uncontrolled **Hypokalemia** associated with **metabolic alkalosis**, without the use of diuretics Features of an underlying cause, such as hyperglycemia in the setting of Cushing's syndrome

Answer 140

Renal: Renovascular hypertension, renal parenchymal hypertension Endocrine: Primary hyperaldosteronism, Cushing's syndrome, pheochromocytoma Drugs: licorice (contains *glycerrhetinic acid*) inhibits 11–beta hydroxysteroid dehydrogenase

Answer 141

Renovascular hypertension caused by renal artery stenosis (unilateral or bilateral) _Atherosclerosis causes_ 75–90% of renovascular hypertension, typically in patients \>50 who have cardiovascular risk factors (tobacco use, dyslipidemia, peripheral vascular disease) _Fibromuscular dysplasia_: 10–25% of renovascular hypertension (30–50 years, women\>men)

Answer 142

- Reduced renal perfusion pressure resulting from stenosis of the arterial vasculature in one of both kidneys - Decrease in renal perfusion pressure activates RAAS - Angiotensin II stimulation causes the following that results in sustained hypertension: 1. Increase in sympathetic nervous system activity 2. Vasoconstriction 3. Anti-diuretic hormone release (water retention) 4. Aldosterone release from the adrenal gland (sodium retention)

Answer 143

**Magnetic resonance angiography**: highly sensitive, specific, and noninvasive. This is the modality of choice. However, it cannot be used in patients with GFR of \<30 ml/min due to the contrast agent. **CT spiral angiography with contrast**: High sensitivity and specificity. Risk of nephrotoxicity in patients with impaired GFR due to the contrast agent. **Duplex doppler ultrasonography**: Time consuming test with moderate sensitivity and specificity. Results are operator-dependent. However, no contrast, so safe for patients with impaired GFR. Standard for diagnosing fibromuscular dysplasia (10–25% of renovascular hypertension) **Conventional renal arteriography**: Gold standard for diagnostic investigation of renal artery stenosis. Usually used pre-intervention. Risks include damage to femoral or renal artery; cholesterol embolization; contrast-induced nephrotoxicity.

Answer 144

1. Treat with **antihypertensives** and **lipid lowering therapy** (if appropriate) 2. Patients with fibromuscular dysplasia should try ACE inhibitor or ARB; if remain hypertensive, then can have percutanous transluminal angioplasty (PTA) 3. Patients with atherosclerosis should use antihypertensives, lipid- lowering drugs, and antiplatelets. PTA is reserved for patients with uncontrolled hypertension with multiagent therapy, or rapid rise in serum creatinine with parenchymal loss.

Answer 145

Pathogenesis is multifactorial. Includes volume expansion via sodium and water retention, RAAS activation, activation of the sympathetic nervous system, endothelial dysfunction, and secondary hyperparathyroidism (intracellular calcium promotes constriction of vascular smooth muscle) Most common treatment ACE inhibitor or ARB; diuretic to remove excess volume; calcium channel blocker if a third agent is needed

Answer 146

Plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio; if the ratio is \> 30–50 and the PAC is \>=15, then suggestive of primary hyperaldosteronism \*Aldosterone antagonists (spironolactone) must be discontinued for 6 weeks before testing Confirmatory testing: sodium loading for 3 days, followed by 24 hours urine collection. Normally, aldosterone will fall with this high salt intake. If it is still high, urinary levels will be \>14 ug, and indicates primary hyperaldosteronism Can also do normal saline administered over 4 hours, followed by a plasma aldosterone level. Aldosterone should be \<5 ng/dL; if \>10ng/dL, confirms primary hyperaldosteronism CT, adrenal vein sampling used to distinguish between adenoma, carcinoma, or adrenal hyperplasia Treatment: laparoscopic removal of adenoma. If adrenal hyperplasia, treat with spironolactone indefinitely.

Answer 147

**Centripetal obesity**: fat deposition in the face, neck, trunk, abdomen **Moon facies**: fat accumulation in the cheeks, temples **Skin atrophy and abdominal striae**: broad purple streaks **Acne and hirsutism**: increased hair on upper lip and chin due to androgen excess **Proximal muscle weakness** **Hypertension** **Glucose intolerance**

Answer 148

**Diagnosis** 1. _24 hour urinary cortisol excretion_; positive test if concentration is 3x upper limit of normal 2. _Late evening salivary cortisol_ 3. _Low dose dexamethasone suppression test_: dexamethasone suppresses ACTH release, leading to a suppression of cortisol secretion. A normal test is \<50 nmol/L. If **two** of the tests are abnormal the diagnosis is confirmed. **Treatment** Transphenoidal resection (through the nose) of the pituitary adenoma; pituitary irradiation In the case of adrenal tumors, remove the adrenal glands. In the case of other tumors secreting ACTH, remove the tumor

Answer 149

Catecholamine-secreting tumors that arise from the adrenal medulla Triad of headache, sweating, tachycardia and hypertension. Symptoms may be precipitated by triggers (pain, trauma, drugs, foods)

Answer 150

24 hours fractionated urinary metanephrines and catecholamines (NE, epinephrine, dopamine, normetanephrine); highly sensitive and specific for pheochromocytoma Fractionated plasma metanephrines: simpler to perform test; first line. High sensitivity but low specificity (85%) CT or MRI of the abdomen and pelvis detects most tumors; many incidental adrenal adenomas picked up, so not very specific MIBG scinitigraphy: can scan to detect tumors if CT is negative Treatment: Surgical removal of the tumor Control blood pressure first Use _Alpha antagonists are first-line_, like **phenoxybenzamine**, 7–10 days before surgery (long acting), or **phentolamine**, a shorter acting alpha antagonist After HTN is controlled, use beta blockers to prevent tachycardia. If alpha blockade is not achieved, do not use beta blockers. Can also add **nifedipine** (calcium channel blocker) if needed _Acute hypertensive crisis_ can occur during surgery; treat with parenteral **nitroprusside, phentolamine, nicardipine**

Answer 151

Association of obestity, obstructive sleep apnea, and hypertension have long been established. Apnea may contribute *directly to hypertension due to* *abnormalities of sympathetic nervous system function and vascular reactivity*

Answer 152

Daytime sleepiness, morning headache, snoring or witnessed apneic episodes, poor concentration 30–80% of patients with essential hypertension have obstructive sleep apnea 50% of patients with obstructive sleep apnea have hypertension **Polysomography** (sleep study)

Answer 153

Weight loss, avoidance of alcohol, and sedating medications (benzodiazepines, antihistamines) - depress the CNS Continuous positive airway pressure (CPAP) splints the upper airway open Oral appliances to hold the tongue and mandible more anterior Surgical therapy: uvulopalatopharyngoplasty (UPPP) for those with correctable obstructing lesion

Answer 154

**The presence of either kidney damage or decreased kidney function for _\> or equal to 3 months_ with or without decreased glomerular filtration rate (GFR)** Kidney damage can be determined by: Pathological: kidney biopsy Clinically, as proteinuria (\>150 mg, or \>30mg albumin), glomerular hematuria (dysmorphic RBCs, RBC casts), or on imaging (polycystic kidneys, hydronephrosis, small kidneys) \*GFR can be normal and still have kidney damage pathology!

Answer 155

Derived from the metabolism of **creatine** in skeletal muscle and from dietary meat intake --\> released into circulation at constant rate --\> stable plasma concentration Freely filtered across the glomerulus and is neither reabsorbed nor metabolized. **It is inversely proportional to GFR** **\*Limitations**: not accurate in patients w/ **little muscle mass, dwarfism** Creatine is **secreted** by organic secretory pathway in PCT and certain meds (Trimetheprim-Sulfamathoxazole, Cimetadine) inhibit secretion. Only useful when GFR is low, as creatinine changes little until GFR is \<60 ml/min

Answer 156

**Clearance = UV / P** U=urinary concentration of a substance, V=volume of urine per set time (in this case 24h), P=plasma concentration of a substance **\*Limitations:** since creatinine is also secreted at PCT, urinary [creatinine] will be higher than was actually filtered --\> creatinine clearance will excedd the true GFR by 10-20% Also patients tend to over or under collect urine (i.e. in 24 hour sample), so hard to get an accurate clearance. Not recommended for routine GFR assessment.

Answer 157

Estimates GFR by incorporating known demographic and clinical variables as observed surrogates for unmeasured factors other than GFR that affect serum creatinine Increasingly used not only to estimate GFR but follow changes in GFR Becomes less accurate when GFR \>60ml/min

Answer 158

Also estimates GFR based on age, gender, ethnicity, and creatinine . Better accuracy than MDRD when GFR \>60ml/min (may eventually replace MDRD; for now MDRD is used most often in the US)

Answer 159

Stage 3 has been recently modified to **3a (GFR 46-59)** and **3b (31-45)** given association with higher mortality at GFR \<45ml/min (particularly with cardiovascular events)

Answer 160

initial kidney insult --\> **nephron loss** --\> remaining nephrons will hyperfilter (same GFR) --\> **glomerular capillary hypertension** --\> **cytokine activation** and **podocyte dysfunction** --\> proteinuria, glomerular sclerosis, tubulointerstitial fibrosis ==\> **Renal scarring**

Answer 161

DM --\> mesangial expansion, thickening of GBM, glomerulosclerosis --\> _hyperfiltration/ glomerular capillary HTN_ --\> _Microalbuminuria_ (30-300mg) --\> _Macroalbuminuria_ (\>300mg) Or, the disease may progress w/o albuminuria

Answer 162

*polymorphisms* of APOL1 gene give **selective biological advantage** - resistance against *Trympanasoma brucei rhodesiense,* however, when inherited in recessive fashion --\> HTN CKD with higher progression to ESRD Stuff associated w/ longstanding HTN: **retinopathy****, LV hypertrophy, proteinuria** (\< 1g/day)

Answer 163

**Most patients with stages 2–4 chronic kidney disease die from cardiovascular causes**, and do not progress to end-stage renal disease CKD patients have a high risk for developing cardiovascular disease, even when controlling for other shared risk factors, due to decreased GFR and increase in proteinuria Patients will also have **HTN**: Na+ retention; High RAAS; High SNS; secondary hyperparathyroidism --\> vasoconstrict (more Ca²⁺) patients also have decreased urinary phosphorus excretion --\> compensatory increase in **FGF-23 (phosphatonin)**; increases phosphate excretion --\> decrease in 1,25-VitD (FGF inhibits) --\> decrease serum Ca²⁺--\> **increase in PTH** --\> can lead to osteomalacia, osteitis fibrosa, vascular calcification **Anemia** - decreased EPO secretion from kidney

Answer 164

1. Proteinuria \> 1.0 grams per day 2. Hypertension 3. Type of underlying disease (i.e. diabetes mellitus, polycystic kidney disease) 4. African-American race 5. Male gender 6. Obesity a. Increases glomerular capillary pressure 7. Hyperlipidemia a. High lipid levels are associated with a faster rate of progression 8. Smoking 9. Hyperphosphatemia 10. Metabolic acidosis a. Bicarbonate supplementation appears to slow progression of CKD b. Mechanism thought to be due to reduction in tubulointerstitial inflammation 11. High protein diet a. Increases glomerular capillary pressure 12. Hyperuricemia a. Data emerging that treatment to reduce uric acid levels may slow the rate of GFR loss

Answer 165

\*The most important intervention is adequate BP control! (\<130/80) (140\<90 in African Americans) Renin-angiotensin-aldosterone antagonism: ARBs, ACEIs Control phosphorus levels: reduce intake or take binders Treat metabolic acidosis: sodium bicarbonate Stop smoking Correct anemia: (EPO) Use a Statin Low protein diet Treat underlying disease - make sure blood sugar control is tight

Answer 166

pre-emptive transplant (transplant prior to dialysis)

Answer 167

inscreases ammonia production (derived from metabolism of glutamine) with a resultant increase in NH4+ (ammonium) in the urine

Answer 168

Peristaltic contractions propel the urine towards the bladder (2–6 cm/s). Pacemaker cells initiate the spontaneous action potentials that lead to contractions. The fastest pacemaker cells are located in the calyces. Urine enters the bladder at the ureterovesical junction; since pressure in the bladder is normally low, it fills easily. \*If the ureter is blocked (by a stone, for example) or if the bladder pressure is high (neurologic disease), then the ureter becomes distended and hydronephrosis occurs. If unilateral, the other kidney can compensate. If bilateral, can cause kidney failure or irreversible kidney damage. Very serious.

Answer 169

The bladder is composed of diffuse smooth muscle fibers. It contains a body and a base; the body is distensible to allow filling with urine, while the base is fixed, and is where urine enters and exits. The bladder base contains the trigone and bladder neck (point which connects to the urethra) The bladder outlet includes structures involved in continence and voiding: bladder base, urethra, external sphincter The bladder neck and proximal urethra are the internal sphincter, which does contribute to continence

Answer 170

Female: The urethra is fused to the anterior wall of the vagina. It is short in females. Primary zone of continence is the external sphincter, located at the urogenital diaphragm. It is augmented by the pelvic floor muscles. Continence is promoted by the tone of the external sphincter; the support of the anterior wall of the vagina; and the coaptation of the anterior and posterior walls of the urethral lumen (sticking together). Childbirth, nerve damage, loss of estrogen all impact continence in women. Urinary incontinence is more common in women.

Answer 171

Male: Primary zone of continence is the external sphincter, located at the membranous urethra. It is augmented by the pelvic floor muscles. There is a secondary zone of continence located at the bladder neck/prostatic urethra that closes during ejaculation and contributes to continence. Areas of the long male urethra are the: prostatic urethra; membranous urethra; bulbar urethra (penile base); and the pendulous urethra (penile shaft).

Answer 172

The detrusor muscle is rich in muscarinic cholinergic receptors; activation of these **M3 receptors** results in contraction of the detrusor (parasympathetic activation = elimination mode) During contraction of the detrusor, it is thought that a second system using nitric oxide is activated to relax the bladder base/outlet and allow for elimination The dome of the bladder (body) has many beta adrenergic receptors; activation of these **Beta-3 receptors** results in relaxation of the detrusor (sympathetic activation = storage mode) The *base of the bladder* and *proximal urethra* have many alpha adrenergic receptors; activation of these **Alpha-1 receptors** (NE) results in contraction of the bladder neck, promoting storage of urine (sympathetic activation = storage mode). Males have more Alpha-1 receptors in the bladder neck to prevent retrograde ejaculation into the bladder during ejaculation.

Answer 173

The detrusor must be relaxed, while the outlet and external sphincter must be contracted. The bladder is normally very compliant; it fills at low pressure and can stretch a great deal (compliance is volume change over pressure change) There are afferents that detect the amount of stretch in the bladder wall; this information is sent to higher centers and affects the decision to void People with stiff/ non-compliant bladders will be signaled to void at lower volumes. In storage mode, the cortex inhibits the PMC (pontine micturition center). As the bladder fills, afferent fibers are fired, activating a reflex in the lumbar and sacral spinal cord. This reflex causes an outflow of sacral somatic activity via the pudendal nerve that contracts the external sphincter, and sympathetic activity that: **Relaxes the detrusor via beta 3 receptors** **Contracts the muscle of the bladder neck and urethra via alpha 1 receptors** **Inhibits parasympathetic transmission from the ganglia in the wall of the bladder**

Answer 174

The detrusor muscle contracts, and the outlet relaxes. The cortex decides to void, releasing inhibition of the PMC (pontine micturition center). This sends signals to the lumbar (sympathetic) and sacral (parasympathetic) cord to do the following: **Inhibit the pudendal nerve, allowing the external sphincter to relax** **Inhibit the hypogastric nerve lumbar sympathetics, which aborts the actions discussed above, i.e. aborts the guarding reflex** **Stimulates parasympathetic outflow from the sacral micturition center, causing contraction of the detrusor and relaxation of the bladder neck and proximal urethra** **The PMC can make the decision to void in the absence of cortical input**

Answer 175

Acetylcholine activates muscarinic M3 receptors on the detrusor. This inhibits the neurons in the parasympathetic ganglion from firing, as well as activates a G-protein coupled mechanism that activates phospholipase C (PLC). PLC activation results in the generation of IP3. This leads to opening of calcium channels in the cell membrane and in the sarcoplasmic reticulum, causing increased contraction of the smooth muscle. Calcium binds to calmodulin, which then activates myosin light chain kinase. MLCK phosphorylates the myosin light chain, and contraction occurs (via cross-bridging to actin). ATP is hydrolyzed slowly, and the force generated lasts for a relatively long period of time.

Answer 176

Adrenergic activation of beta-3 receptors in the detrusor causes activation of adenylyl cyclase, which increases cAMP in the cell. Increased cAMP prevents phosphorylation of the myosin light chain, preventing cross-bridging and thus leading to relaxation of the muscle.

Answer 177

the detrusor contracts involuntarily, causing a sudden need to urinate (urge incontinence). The patients may not be able to make it to the bathroom when this urge comes on. Characterized by urinary urge and urinary frequency. Failure to store due to the bladder (Wein)

Answer 178

abnormal function of the bladder outlet. May be a problem with the bladder neck or with the urethra. Patients report stress incontinence (urination with coughing, laughing, etc). In women, it occurs after menopause or after vaginal childbirth. In men, it typically occurs after prostate surgery due to damage to the pedundal nerve. Failure to store due to the outlet (Wein).

Answer 179

the bladder is unable to empty, either due to an obstruction or a failure of the detrusor to contract. As a result, the bladder becomes completely distended with urine, and the urethra continuously leaks. Failure of the bladder to empty (Wein)

Answer 180

can occur, and clinically this often presents as stress incontinence and urge incontinence together.

Answer 181

Due to a problem of the outlet Due to a problem of the bladder Due to a problem of both bladder and outlet (mixed)

Answer 182

Due to a problem of the outlet Due to a problem of the bladder Due to a problem of both bladder and outlet (mixed)

Answer 183

Bladder capacity and compliance Bladder sensation The detrusor pressure at which the bladder stores and empties urine; the urinary flow rate produced by the voiding detrusor pressure Determine if the bladder is obstructed by examining the pressure-flow relationship during micturition Determine if the bladder exhibits detrusor overactivity, which can lead to urinary incontinence Determine the presence of a weak urinary sphincter and the intravesical pressure at which incontinence occurs due to the weak sphincter

Answer 184

For lesions above the brainstem, patients have detrusor overactivity. This occurs because there is less inhibition on the PMC, causing the PMC to initiate voiding more frequently. Urinary frequency, urgency, nocturia, urge incontinence.

Answer 185

For lesions in the brainstem, the patient will have complex and variable voiding dysfunction (if they survive)

Answer 186

Immediately after spinal cord injury, regardless of the level, there is a period of spinal cord shock in which there is decreased excitability at and below the lesion. Usually this causes an areflexic, non-contractile bladder with a closed bladder outlet. The bladder fails to empty due to both the bladder and the outler (overflow incontinence).

Answer 187

For lesions above S2 (thoracic spinal injury): the patients typically have detrusor sphincter dyssynergia. Voiding is not coordinated due to lack of input from the PMC. The external sphincter cannot relax due to lack of input from the PMC, and tends to contract as the detrusor contracts. Spinal reflexes attempt to empty the bladder, but cannot due to contraction of the external sphincter; the detrusor is hyperactive and the bladder does not empty completely. Failure to empty due to the outlet, and failure to store due to the bladder.

Answer 188

For lesions below S2 (upper lumbar or lower thoracic injury): the patients typically have detrusor areflexia and a fixed external sphincter. The bladder fails to contract and the external sphincter remains contracted due to lack of voluntary control. Urinary retention with overflow incontinence (failure to empty due to the bladder).

Answer 189

Obstructive uropathy causes weak and intermittent urinary stream; urinary hesitancy; straining to void; sensation of incomplete emptying. In early obstructive uropathy, the detrusor will thicken to compensate for the obstruction. This causes the detrusor to become overactive, leading to urinary urgency and urge incontinence. Urinary frequency increases, because the bladder does not empty completely and the functional capacity is reduced. With later stages, the bladder decompensates and can no longer empty. Post-void residuals increase. Untreated, it will progress to urinary retention with hydronephrosis, which can progress to renal failure in some cases.

Answer 190

volatile comes from CO2 (excreted from the lungs) = 24,000 mMol produced per day from normal metabolism non-volatile: derived from the metabolism of certain amino acids, phosphorus-containing compounds, and organic acids. They are excreted by the kidneys. 50–100mEq is produced per day by normal metabolism. - Excretes acids by combining ions with urinary buffers to form titratable acid or with ammonia to form ammonium - Reabsorbs bicarbonate

Answer 191

If respiratory acidosis develops, the kidneys will compensate by increasing H+ secretion and increasing bicarbonate (via ammoniagenesis, which increases the amount of ammonium in the urine) If respiratory alkalosis develops, the kidneys will compensate by increasing bicarbonate secretion Acid produced by normal metabolism is excreted by the lung (CO2) and the kidneys (nonvolatile acids) to maintain acid/base balance

Answer 192

It is used to calculate pH based on the ratio of bicarbonate to carbon dioxide tension (i.e. the arterial blood gas partial pressure of carbon dioxide)

Answer 193

characterized by a decrease in pH as well as a decrease in bicarbonate

Answer 194

characterized by an increase in pH as well as an increase in bicarbonate.

Answer 195

characterized by a decrease in pH, and an increase in dissolved carbon dioxide (pCO2)

Answer 196

characterized by an increase in pH and a decrease in dissolved carbon dioxide (pCO2)

Answer 197

Metabolic acidosis: to compensate for the decrease in pH, ventilation increases in an attempt to reduce pCO2 and raise the pH. This does not raise the pH all the way to normal but does raise it towards normal.

Answer 198

Metabolic alkalosis: the respiratory compensatory response is variable and takes hours to develop. The response is hypoventilation in an attempt to raise pCO2 and lower the pH. The pCO2 can only rise to about 55–60 mmHg. Often patients have other disease states and symptoms that cause hyperventilation, thus counteracting the compensatory response

Answer 199

Respiratory acidosis: acute response is increase in plasma bicarbonate (from non-carbonic acid buffers). Chronic (~72 hours) response is an increased acid excretion from the kidneys due to increased ammoniagenesis, with bicarbonate retention

Answer 200

Respiratory alkalosis: acute response is due to H+ released from non carbonic acid buffers. Delayed response in the kidneys of increased HCO3– excretion, reduced excretion of ammonium and titratable acid. In chronic cases, the pH can return to within normal range.

Answer 201

Total cations = total anions in blood (no net charge) The anion gap is calculated by Na+ — (HCO3– + Cl-) The normal range for anion gap is 8–12 mEq/L Albumin can affect the anion gap. The anion gap falls 2.5 mEq/L for each 1 g/dL reduction in albumin below the normal range. Corrected AG = AG + 2.5(4–measured albumin)

Answer 202

Elevated anion gap metabolic acidosis occurs due to a gain of nonvolatile acid, while normal anion gap acidosis occurs due to a loss of base.

Answer 203

In respiratory acidosis, the kidneys reduce or eliminate HCO3 excretion in the urine; in addition, they increase titratable acids and ammonium excretion. This increases the net acid excretion in an attempt to raise the pH. In respiratory alkalosis, the kidneys at first release H+ from non-carbonic acid buffers; later, there is an increase in excretion of bicarbonate, and reduced excretion of ammonium and titratable acid.

Answer 204

Metabolic alkalosis is a primary disorder that causes the plasma bicarbonate (HCO3–) to rise. The pathogenesis of this disorder requires both the generation and maintenance of this process. Decreased renal excretion of HCO3– (often related to Cl- depletion or deficiency) Causes include **GI H+ loss** **(vomiting, NG suction), renal H+ loss due to diuretics (loop and thiazides)**, primary mineralocorticoid excess, Bartter's, Gitelman's, & Liddle's Syndromes, or alkali administration

Answer 205

History and physical examination Check the pH. Is the patient acidemic or alkalemic? Look at pCO2 and HCO3–. Is the disorder respiratory or metabolic? Is there appropriate compensation? Is there an elevated anion gap? (This may be the only clue to a mixed acid-base disturbance)

Answer 206

**Light Microscopy** (Basic morphology) **Immunofluorescence Microscopy** (Immune deposits) **Electron Microscopy** (Ultrastructure) \*all samples must have cortex and glomeruli

Answer 207

**Nephrotic syndrome**: dysfunction of glomerular podocyte Proteinuria (\>3.5gm/24hrs) **Hypoalbuminemia** - pitting edema **Hypogammaglobulinemia** - increased risk of infection **Hyperlipidemia/ lipiduria** - may result in fatty casts in urine **Hypercoagulable state** - due to loss of antithrombin III

Answer 208

Clinical condition associated w/ glomerular capillary dysfunction/inflammation (active glomerulonephritis) Hematuria Proteinuria increased BP Edema increased serum creatinine Active urinary sediment - Red blood cells and casts (made of red blood cells, white blood cells and/or epithelial cells) detected in the urine; indicates active glomerulonephritis **Rapidly progressive glomerulonephritis** - severe form of acute nephritic syndrome w/ a rapid rise of serum creatinine (renal emergency)

Answer 209

Usually subnephrotic range proteinuria (\< 3.5 gm/24 hours) or persistent/recurrent microscopic hematuria.

Answer 210

- Elevated serum creatinine Acute - Glomerular, vascular or tubulointerstitial disease Chronic - Advanced renal disease, usually irreversible, due to a variety of primary diseases.

Answer 211

_Overall dysfunction of podocyte_ **Glomerular proteinuria**: abnormalities in the podocytes allows for increased filtration of macromolecules across the glomerular capillary wall. Albumin is the principal urinary protein. **Hypoalbuminemia**: consequence of urinary albumin losses. Hepatic synthesis of albumin increases, but it cannot replete the serum levels. **Edema**: Due to hypoalbuminemia, plasma oncotic pressure is decreased and fluid moves into the interstitial space. Decreased effective vascular volume causes activation of RAAS, and leads to sodium and water retention (aldosterone) and reduced ANP release. **Hyperlipidemia, lipiduria**: Decreased oncotic pressure stimulates the liver to produce lipoproteins, which manifests as hypercholesterolemia, hypertriglyceridemia. The lipid in the urine becomes trapped in protein material in the tubules; lipid casts. Oval fat bodies (enclosed by cytoplasmic membrane of degenerated cells)

Answer 212

Altered Coagulation --\> Thromboembolism Loss of anticoagulant factors thru glomerular capillaries (antithrombin II) into urine leads to increased pro-coagulant production in the liver. Volume depletion from diuretic therapy + reduced oncotic pressure in the vasculature leads to concentration of blood, and increased platelet aggregation. _Renal vein thrombosis Infection_ - loss of fluid across glomerulus, hemoconcentration in post-glomerular circulation \*Infection Due to immunoglobulin loss in the urine Staphylococcus, Streptococcus pneumoniae are common

Answer 213

**ACEi** or **ARB** (reduce intraglomerular pressure, reduce proteinuria) Loop diuretics, low Sodium diet Strict BP control (\<130/80) Statin to treat hyperlipidemia

Answer 214

**Primary Gomerular Diseases: "immune podocytopathies"** a. Membranous nephropathy b. Minimal change disease c. Primary focal segmental glomerulosclerosis (FSGS) d. Idiopathic/autoimmune membranoproliferative glomerulonephritis **Secondary - Systemic Diseases** a. Diabetic nephropathy b. Amyloidosis c. Systemic lupus erythematosis

Answer 215

Most common cause of nephrotic syndrome in children (90% \<5 years, 50% \>10 years) Etiology: idiopathic, NSAIDs, or neoplasm (Hodgkin's disease, lymphoma, leukemia Pathogenesis: Systemic T cell dysfunction produces a glomerular permeability factor (**cytokines**) that injures podocytes. Foot processes flatten and merge, causing selective proteinuria (loss of albumin, but not immunoglobulin) On light microscopy, not much evident (“minimal change”). Immunofluorescence is negative. On EM, see diffuse _effacement of podocyte foot processes_. Nonspecific Diuretic/Low Na+; _High Dose Sterioids_ (prednisone); Cyclophosphamide (steroid dependent); Cyclosporine (steroid resistant patients)

Answer 216

Etiology: Idiopathic, Genetic/familial (involves genes encoding _slit diaphragm proteins_) \*Most common in Hispanics/ African Americans Pathogenesis is systemic T-cell dysfunction (as in MCD; on the same disease continuum, but FSGS is less responsive to treatment) Presence of a circulating toxin (supported by rapidity of relapse after transplant) On light microscopy, see **focal glomerular sclerosis of a segment of the glomerular capillary tuft**. Immunofluorescence: Trapping of C3 and/or IgM in areas of sclerosis. Electron: _Diffuse effacement_ of podocyte foot processes \*May present with acute or insidious onset --\> ESRD (if untreated) Treatment: – Nonspecific therapy (ACEi/ARB/loop/lowNa+/BP control/statin for hyperlipidemia); High Dose steroids (prednisone); if no response, then may have _familial FSGS_

Answer 217

Secondary etiology occurs in many forms of renal injury and systemic disease: loss of renal mass, obesity, **HIV**, **sickle cell disease**, drugs (pamidronate, **heroin**) Pathogenesis related to **hyperfiltration** + **increased glomerular capillary hypertension** that causes podocyte injury; or direct injury to the podocyte from a virus (HIV) Presents with nephrotic range proteinuria, rather than the full nephrotic syndrome (absence of hypoalbuminemia, lipid abnormalities) On light microscopy, see focal glomerular sclerosis of a segment of the glomerular capillary tuft. On immunofluorescence, no specific immune complex deposition On EM, see diffuse podocyte foot process effacement in primary FSGS; variable effacement in secondary FSGS **onset is always insidious** If untreated then leads to ESRD

Answer 218

Antigen-antibody complexes form in the blood and then become trapped in the renal tissue. Circulating antigen deposits in the kidney, then the antibody binds to it. Renal proteins act as auto antigens, and then antibodies recognize and bind to them.

Answer 219

most common nephrotic syndrome in Caucasian adults Primary/idiopathic (70%); Secondary (30%): Hep B and C, Malignancy, SLE, drugs (NSAIDs, penicillamine) Pathogenesis: Primary - Autoimmune disease w/ IgG antibodies directed against T**ype-M phospholipase A2 receptor** on podocyte foot process. Secondary: caused by circulating IgG antibodies against extrinsic antigens from viral proteins, tumor proteins, drug-related substances. Immune complex activates complement cascade, causing assembly of the membrane-attack complex (MAC) which inserts into the podocyte membrane, causing podocyte injury --\> **proteinuria** (podocyte foot process effacement; loss of podocytes from apoptosis and necrosis. Light Microscopy: Thick GBM w/ "spike and dome" appearance Immuno/Electro: subepithelial granular deposits **Spontaneous remission occurs in up to 30% of patients at 5 years. Progresses to ESRD in 40% at 15 years if not treated.** Nonspecific therapy: ACEi/ARB, loop diuretic, low Na+, BP control, statin for hyperlipidemia. If persists: Cyclophosphamide + prednisone x 6 months

Answer 220

most common cause of ESRD in the US Hyperglycemia leads to nonenzymatic glycosylation of vascular basement membrane resulting in _hyaline ateriolosclerosis_. Glomerular Efferent arteriole more affected leading to High glomerular filtration pressure --\> **Microalbuminuria** --\> nephrotic syndrome: Sclerosis of the mesangium with formation of _Kimmelsteil-Wilson nodules_ ACEi/ARB reduce glomerular capillary pressure; Strict blood sugar control

Answer 221

caused by extracellular deposition of abnormally folded proteins that deposit in the mesangium, resulting in nephrotic syndrome. **AL type** (primary) - Multiple myeloma; amyloid made of _monoclonal immunoglobulin light chains_ **AA type** (systemic reactive) -chronic inflammatory disease (RA, inflammatory bowel, hepatitis); amyloid made of _serum amyloid A protein_ Characterized by **apple-green birefringence** under polarized light after staining with **Congo red**; haphazardly arranged fibrils Treatment: Nonspecific ACEi/ARB/loop/low Na+diet /BPcontrol/hyperlipidemia Primary: Chemotherapy, Peripheral stem cell transplant Secondary: Treat underlying disease

Answer 222

infection of the bladder can lead to \**SCC* Presents as dysuria, urinary frequency, urgency, suprapubic pain, systemic signs are usually absent (fever, chills) *E coli* (80%) \>\>\> Proteus, Klebsiella, Enterobacter, Schistosoma (middle eastern countries) Urinalysis - cloudy urine w/ \> 10 WBCs/ high power field Dipstick - Positive Leukocyte esterase (due to pyuria) and nitrites (bacteria convert nitrates to nitrites) Culture - greater than 100,000 colony forming units

Answer 223

Gross: Hyperemia of mucosa, gray-tan exudate Hemorrhage Microscopic: Neutrophilic infiltrate, hemmorrhage, ulceration of mucosa

Answer 224

Hyperemia of mucosa Chronic infiltrate, mostly lymphocytes, plasma cells; reactive-appearing epithelium; Fibrosis and thickening of muscularis propria (decreased contractility)

Answer 225

Chronic Follicular Cystitis - aggregation of lymphocytic infiltrate with lymphoid follicles

Answer 226

Eosinophilic Cystitis -submucosal eosinophilic infiltrate, fibrosis and occasional giant cells due to allergies, parasites, or idiopathic

Answer 227

Malacoplakia unique form of chronic cystitis; caused by *E Coli* infection immunosuppresed patients (esp. transplant) Gross: multiple yellowish plaques in mucosa and submucosa Micro: Large foamy macrophages, multinucleate giant cells, lymphocytes, **Michaelis-Gutmann bodies** (round, intracytoplasmic concretions, thought to represent defects in phagocytosis)

Answer 228

Polypoid cystitis inflammation resulting from irritation to bladder mucosa (commonly indwelling catheter) Broad, polypoid mucosal projections due to submucosal edema Can be confused w/ papillary urothelial carcinoma

Answer 229

Emphysematous cystitis -Inflammation associated with formation of air-filled spaces

Answer 230

Cystitis cystica - Nests of transitional epithelium gown downward into lamina propria; may have central cystic spaces - Can be seen in normal bladders, but also in the setting of inflammation and metaplasia

Answer 231

most frequent in women - Inflammation and fibrosis in all layers of the bladder wall, often with ulceration – Can mimic gross appearance of carcinoma in situ (CIS) - Highly incapacitating and difficult to treat - suprapubic pain, frequency, urgency, hematuria, dysuria

Answer 232

caused by **ascending infection from bladder** from gram negative rods **E coli**, Klebsiella, Enterobacteria

Answer 233

**Urinary tract obstruction w/ urine stasis** **Instrumentation** of urinary tract (including bladder catheters) **Vesicoureteral reflux** **Pregnancy** (due to higher incidence of bacteriuria, UTI, and thus pyelonephritis) **Renal Disease** **Diabetes Mellitus** **Immunosuppresion**

Answer 234

Colonization of urethra then bladder (usually intestinal flora) Bacterial adhesion molecules interact with receptors on the urothelium for adhesion (P- fimbriae) --\> promote migration Multiplication of organisms in bladder from outflow obstruction, bladder dysfunction --\> STASIS --\> bacterial growth The organism moves to the upper tract, either due to instrumentation/catheterization, or due to _Vesicoureteral reflux_ from the bladder back up the ureters (occurs during micturition) As urine refluxes, it moves from the renal pelvis to the medulla (**intrarenal reflux**), and can move back into collecting ducts at the compound papillae of the upper/lower kindey poles (they have a divet in the middle that allows this to occur)

Answer 235

Fever, flank pain, WBC casts, generalized constitutional symptoms of cystitis (urgency, frequency dysuria) Laboratory findings: **leukocytosis with left shift**; **pyuria** (leukocytes in urine); **leukocyte casts** in urine (upper urinary tract disease); **positive urine culture**; **positive blood cultures** in 15–30% of patients (diabetics, elderly, immunosuppressed)

Answer 236

acute pyelonephritis Focal abscesses or confluent, wedge-shaped areas of suppuration Patchy neutrophilic infiltrate in interstitium and within tubules; abscess formation with destruction of engulfed tubules

Answer 237

acute pyelonephritis Patchy neutrophilic infiltrate in interstitium and within tubules; abscess formation with destruction of engulfed tubules

Answer 238

most cases recover with antibiotics, usually never progress to disease, but bacteria may still be present in urine (culture) Complications: **Bacteremia/sepsis** - 15-30% **Papillary necrosis** - usually seen in diabetics **Pyonephrosis** - exudate fills renal pelvis and ureters, seen in severe obstruction **Perinephric abscess** - inflammation spreads into perinephric fat

Answer 239

Important viral cause of acute pyelonephritis in **renal allografts** immunosuppresion leads to reactivation of latent virus w/ infection of renal tubular epithelial cells, resulting in tublointerstitial inflammation (**intranuclear viral inclusionsb** in tubular cells)

Answer 240

interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis due to vesicoureteral reflux (children) or chronic obstruction (BPH or cervical carcinoma) Leads to cortical scarring with blunted calyces; scarring at upper and lower poles - vesicoureteral reflux

Answer 241

is a hypersensitivity reaction _Penicillins_ NSAIDs antibiotics - cephalosporins, sulfonamides diuretics - thiazides acetaminophen (rare)

Answer 242

Fever, Skin rash, Eosinophilia, acute renal insufficiency - 50% patients, abnormal liver chemistries, Eosinophiluria _Not dose dependent_ w/ drug use; onset usually after 2 weeks on drug Treat by discontinuing the causative drug; put on steroids; supportive care Continuing the drug may cause permanent injury to the kidney due to scarring

Answer 243

Abnormal synthesis of large amounts of **immunoglobulin light chains** (Bence Jones protein) by the neoplastic plasma cells Light chains **directly toxic** to renal tubular cell epithelium Light chains combine with Tamm-Horsfall protein and form **obstructive casts** within the tubules tubular cell injury causes reactive inflammatory response and edema --\> can lead to chronic injury (fibrosis) Histology: large casts in tubular lumen --\> Giant cell reactions --\>plasma cells, lymphocytes. Late = interstitial fibrosis

Answer 244

Steroids, tetracycline antibiotics, or reabsorption of blood in GI tract

Answer 245

* Glomerular disorders characterized by glomerular inflammation and bleeding.* 1. **Limited Proteinuria** (150mg - 3.5 g/day) MPGN/Lupus Nephritis \>3.5 2. **Oliguria** (\< 500 ml urine per day) 3. **Azotemia** (BUN:Creatinine ratio \> 15) 4. **HTN** due to Salt retention --\> *periorbital edema* **5. Hematuria of glomerular orgin**: RBC casts and dysmorphic RBCs in urine

Answer 246

**Membranoproliferative Glomerulonephritis**: Thick glomerular BM w/ 'tram-track' appearance due to immune complex deposition (granular IF); Renal biopsy is definitive Type 1: subendothelial (associated w/ HBV and HCV) Type 2: **dense deposit disease**; associated w/ C3 nephritic factor (autoantibody that stabalizes C3 convertase, leading to overactivation of complement, inflammation, and low levels of circulating C3); poor response to steroids; progresses to renal failure **Lupus nephritis**

Answer 247

Heaptitis C (HCV, HBV, chronic bacterial infections (subacute bacterial endocarditis, ventriculoatrial shunt infection. Neoplasia: Multiple myeloma, chronic lymphocytic leukemia Pathogenesis: immune complex deposition --\> activate complement (classical pathway) --\> **C3/C4** low in serum; renal biopsy definitive biopsy: duplication of GBM 'tram-track' appearance; granular immune deposits **IgG** and/or **IgM** and **C3** (IF); subendothelial deposits Prolonged course w/ slow rates of disease progression; Poor response to steroids; Progress to chronic renal failure

Answer 248

DDD: overactivation of complement, inflammation, and low levels of circulating C3; associated w/ "Drusen" in Bruch's membrane of retina, and partial lipodystrophy Pathogenesis: **C3** **nephritic factor** (autoantibody that stabalizes C3 convertase, leading to overactivation of complement); deficient/mutated regulatory proteins: **Factor H, Factor I**. Results in persistent degradation Course: DDD has poor prognosis (50% progressing to ESRD in 10 years). It is common for the disease to recur even after transplantation. Prognosis and progression with C3 glomerulonephritis is unknown. Treatment: Nonspecific therapy as with nephrotic syndrome. Can be treated with **plasma exchange** *for patients with C3 nephritic factor* (replace with frozen plasma or albumin to get rid of the factor causing complement activation). For patients with regulatory deficiency, can **infuse with plasma** (do not need to replace). New drug **Eculizumab**: monoclonal antibody to complement protein C5, preventing formation of MAC; very expensive drug, off label use.

Answer 249

MPGN: due to systemic complement activation, serum **C3 and C4 are both low as well as total complement**. DDD: due to alternative complement activation, **only serum C3 and total complement is low**. Assay for C3 nephritic factor, Factor H, Factor I

Answer 250

**MPGN:** LM: _hypercellular, lobulated_ glomeruli; _Duplication of GBM_ ('tram-tracking) IF: IgG, IgM, or C3 _subendothelial_ deposits along GBM/mesangium EM: mesangial/subendothelial immune deposits; Duplication of GBM **DDD**: LM:similar to MPGN, duplication of GBM less prominent IF: mesangial/capillary wall staining w/ C3 EM: Linear deposition of electron dense material along GBM 'ribbon-like' **C3 glomerulonephritis**: Variable patterns of mesangial expansion and cell proliferation on light microscopy. Variable patterns of immune complex deposition on EM; appearance is not as dark in the GBM

Answer 251

Most common glomerulonephritis world-wide (highest asian/causcasian populations) Environemental Ag's trigger mucosal immune response that forms pathogenic IgA immune complexes. *Antigen may be viral (follow upper resp/GI infections), Bacterial, Food*. Pathogenesis: Formation of IgA immune complexes that are *abnormally glycosylated* and cannot be cleared by the spleen. The complexes are recognized as abnormal by the immune system and a second antibody, *IgG*, is formed against it (*they recognize the abnormal hinge region where the glycosylation occurs*). These large macromolecules then deposit in the mesangium of the kidney. Complement is activated. Diagnosis: Renal biopsy. Serum complement is normal, as the activation occurs locally and not systemically. Clinical presentation: ~40% have gross hematuria following URI (synpharyngitic hematuria). ~30% have microscopic *hematuria* and proteinuria discovered incidentally w/ RBC casts. 5–10% present with acute nephritic syndrome, and some present with rapidly progressing glomerulonephritis (RPGN). May be associated with skin or GI abnormalities; dermatitis herpetiformis, celiac sprue, cirrhosis, IgA vasculitis - Henoch-Schonlein Purpura Treatment: Prognosis is variable, with 10–40% progressing to chronic renal failure. If renal function is normal and proteinuria is \<500 mg, then no treatment. If proteinuria \> 1g, then treat with ACE inhibitors or ARBs. Fish oil. Steroids for patients with proteinuria \>1g or with progressive disease.

Answer 252

Epidemiology: Most common cause of acute nephritic syndrome. More common in developed countries (usually seen as children, but also adults) Etiology: Presents _1–6 weeks_ following infectious illness of *streptococcus pharyngitis* or *impetigo* (skin infection) Pathogenesis: _Circulating immune complexes_ (streptococcal ag and ab deposit within glomeruli and activate complement. Elevated antibodies against nephritogenic antigens in patients (AS0: antistreptolysin antibody). OR, Infection causes _alterations of intrinsic proteins within the GBM_ --\>ab to ag--\> compelement Diagnosis: Active urine sediment (dysmorphic RBCs, RBC casts); may have elevated antibody titers (as above); low C3 and total complement with normal C4 due to activation of alternative pathway. Streptozyme test measures 5 different antibodies. Treatment: Care is supportive. Treat the underlying infection. Children have an excellent prognosis, with 95% recovering fully. Adults may have slow insidious progression to chronic glomerulonephritis.

Answer 253

**IgA**: LM: _increased mesangium_ IF: _Mesangial IgA_, C3 EM: _Immune deposits mainly within mesangium_ **Post-infectious glomerulonephritis**: LM: hypercellular glomeruli w/ _abundant PMN's_ IF: granular deposits of IgG, C3 EM: Large, "hump-like" subepithelial deposits

Answer 254

Epidemiology: occurs in _50% patients w/ SLE_ (cause of morbidity/mortality); higher incidence in females and african americans (*lower socioeconomic settings*) Pathogenesis: **Autoimmune disease**: ab's directed at *nucleosomes* form *immune complexes* that deposit in kidney (form in circulation, from intrinsic renal ag, soluble _nucleosomal proteins_), because apoptosis cells not cleared from system properly. Treatment: _Class III-V_ are treated aggressively. _Active lesions_ are treated with **cyclophosphamide** or **cellcept + prednisone**. Other immune therapies: **Azathioprine** (maintenance), **Rituximab** (anti-CD20 antibody) to target B-cells.

Answer 255

LM: variable Focal proliferative pattern (Class III): \< 50% of the glomeruli in the sample show **active lupus lesions** (hypercellularity, immune deposits in capillary or mesangium '**wire loops**' Class IV: \>50% glomeruli show active lupus lesions Class V: Membranous pattern. Has subepithelial immune deposits with spiking of the GBM (similar to membranous nephropathy) _“Full house” immune complex deposition_: IgA, IgG (strongest), IgM, C3, C4, C1q (strong) in mesangium and capillary loops

Answer 256

Membranous lupus nephritis has _subepithelial immune deposits with deposits in the mesangium, without duplication of the GBM_. There is “spiking” of the GBM. Foot processes are still present moreso than in membranous nephropathy (more hematuria than proteinuria). Idiopathic membranous nephropathy has numerous small subepithelial immune deposits with _effacement of the foot processes._

Answer 257

_severe acute nephritic syndrome_ characterized morphologically by *presence of necrosis and crescent formation* on biopsy **Anti-GBM disease**: acute nephritis, may have pulmonary-renal syndrome (*Goodpasture's syndrome*) **Immune complex mediated disease**: IgA nephropathy, Post-infectious GN, Lupus nephritis **Pauci-immune type**: ANCA-associated glomerulonephritis, small vessel vasculitis that targets the glomerular capillaries

Answer 258

Etiology: Usually presents as Goodpasture's in patients \<30. In patients \>50, just present with glomerulonephritis Pathogenesis: formation of autoantibodies to ***type IV collagen*** Course: Rapidly progressive. Needs immediate treatment (renal emergency) Treatment: High dose steroids (IV methylprednisolone over 3 days), cyclophosphamide (3–6 months), azathiprine (maintenance), plasmapheresis Serologic tests: Anti-GBM antibodies

Answer 259

Pathogenesis: ***antineutrophil cytoplasmic antibodies*** (ANCA). No or few immune deposits. Pathogenesis poorly understood. **c-ANCA**: target antigen - **proteinase 3**; associated w/ granulomatosis w/ polyangiitis **p-ANCA**: target antigen - **myeloperoxidase** Course: Rapidly progressive. Needs immediate treatment (renal emergency) Treatment: High dose steroids (IV methylprednisolone over 3 days), cyclophosphamide (3–6 months), azathiprine (maintenance), plasmapheresis Serologic tests: **Anti-GBM antibodies, pANCA, cANCA**

Answer 260

**anti-GBM disease**: LM: necrosis of glomerular capillaries and crescent formation. Non-involved glomeruli look normal. IF: linear IgG along glomerular capillary walls EM: no immune deposits present **pauci-immune glomerulonephritis**: LM: there is necrosis of glomerular capillaries and crescent formation. Non-involved glomeruli look normal IF: nothing lights up EM: no immune deposits present

Answer 261

May be the result of many different etiologies that have progressed to ESRD/renal failure LM: **globally sclerosed**, **Interstitial fibrosis**. **atrophic tubules**, arteriolosclerosis and hyalinosis. _Important point: Morphologic features of chronic GN are often not specific for underlying etiology._ (impossible to determine primary cause because characteristic features are no longer present)

Answer 262

caused by immune complexes containing streptococcal antigens and specific antibodies, which are formed *in situ.* arises after a B-hemolytic streptococcal infection of the skin (impedigo) or pharynx. *granular* immune deposits in the glomeruli indicative of immune complex-mediated mechanism --\> IgG, C3 deposits in mesangium and GBM. enlarged/hypercellular glomeruli "hump-like" deposits: deposit on subendothelial side --\> GBM --\> subepithelial side (\*mechanism not understood)

Answer 263

LOW: C3, C4, and total complement activates classical pathway

Answer 264

PTH --\> osteoblasts --\> osteoclasts PTH increases Ca reabsorption at DCT Convert Vit D --\> Calcitriol, indirectly increases Ca reabsorption in GI tract

Answer 265

Calcitriol increases intestinal calcium absorption. The role in calcium excretion is unclear. (Calcitriol is the active form of Vitamin D, 1,25(OH)2D)

Answer 266

PTH --\> reduced Phosphate reabsorption at PCT due to inhibition of Na+,phosphate cotransporter. PTH also increases phosphate release from bones. Net Effect = *decreased serum phosphate* Calcitriol increases intestinal phosphate absorption, increases renal phosphate reabsorption Phosphatonin (FGF 23). High serum phosphate increases FGF 23.

Answer 267

Chronic Kidney Failure --\> impaired Vit D formation --\> impaired Phosphate excretion --\> CalciumPhosphate binds and is excreted --\> Hypocalcemia Calcitriol stimualtes intestinal Ca²⁺ absorption --\> low Calcitriol levels leads to Hypocalcemia --\> stimulate PTH --\> renal osteodystrophy --\> Increased serum phosphate --\> FGF-23 (inhibits calcitriol/ decrease phosphate reabsorption in PCT) Vitamin D is converted by the proximal tubules of the kidney to the active form. As kidney function is impaired, active vitamin D formation is diminished. Phosphate excretion is impaired as well. Calcitriol stimulates intestinal calcium absorption; low calcitriol levels lead to low levels of calcium absorption in the intestine and lead to low serum calcium levels. Low serum calcium levels stimulate the parathyroid gland to release PTH. This response is mediated by the calcium sensing receptor. Elevated PTH contributes to renal osteodystrophy Increase in serum phosphorus causes an increase in FGF-23, which acts to decrease phosphate reabsorption in the proximal tubule. FGF-23 also inhibits calcitriol.

Answer 268

Abnormal circulating calcium/phosphorus leads to vascular calcification, as vascular smooth muscle cells are capable of producing bone-like proteins Clinical features of kidney disease-mineral and bone disorders: bone pain, muscle weakness, skeletal deformities, growth retardation in children Can be high turnover bone disease, in which PTH is high and the bone structure is disrupted; osteitis fibrosa has increased bone formation/resorption, increased osteoblast/osteoclast activation, peritrabecular fibrosis Adynamic bone disease: low PTH, low bone turnover, decreased osteoblast/clast activity and low rate of bone formation, but mineralization is normal. Osteomalacia: similar to adynamic, with mineralization defect Mixed uremic bone disease: features of osteomalacia and osteitis fibrosa.

Answer 269

Calcium Oxylate

Answer 270

Calcium Carbonate

Answer 271

WBC's - abnormal in urine seen in cystitis or pyelonephritis

Answer 272

Epithelial Cells - abnormal in urine renal tubular or squamous cells

Answer 273

Dysmorphic RBC's - abnormal urine shearing of membranes, indicative of GBM in acute nephritic syndromes

Answer 274

Tyrosine - abnormal in urine

Answer 275

Indinavir - Drug Used for HIV and can precipitate --\> leading to inflammatory response--\> interstitial nephritis Prevent: increase hydration, pH

Answer 276

Cholesterol - abnormal in urine

Answer 277

Struvite (Urea-splitting bacteria) Precipitate in Alklaine urine forming Staghorn Calculus

Answer 278

PCT and TAL ## Footnote *Glomerulonephritis*

Answer 279

Tubulointerstitial disease (interstitial nephritis) Pyelonephritis (infection) Glomerulonephritis (w/ marked inflammation)

Answer 280

_Acute Tubular Necrosis_ (renal tubular cells) Break-down of other cellular casts Waxy (old): Chronic renal disease

Answer 281

Hyaline Casts - nonspecific, seen in normal urine They are seen in low numbers in normal people and are increased in glomerulonephritis, pyelonephritis, congestive heart failure, mental stress and strenuous exercise. They may also increase following use of certain therapeutic and chemical agents.

Answer 282

Red Blood Cell Cast They are seen in diseases with damaged glomerular basement membranes and therefore indicate a highly significant glomerular injury. Diseases that cause acute glomerulonephritis, such as lupus nephritis and anti-GBM disease often have red blood cell casts, but they can also be seen with ischemic injury such as renal infarction

Answer 283

ATN: sequale of epithelial cells being sloughed off --\> cells stretch so there is not 'bare' basement membrane Epithelial Casts seen below

Answer 284

Muddy brown casts seen in ATN

Answer 285

Lipid and protein laden renal tubule seen in *nephrotic syndromes* tubules trying to reabsorb as much protein as possible

Answer 286

WBC Casts seen in Pyelonephritis and Post-infectious glomulonephritis

Answer 287

Waxy casts are seen in Chronic Kidney Injury - urine stasis

Answer 288

Arteriosclerosis: intimal sclerosis (thickening) in response to DM and/or HTN

Answer 289

Arteriolar Hyalinosis (smaller vessels): many proteins get 'stuck' under the endothelium making lumen smaller. Occurs in DM (present in afferent/efferent arteriole) and HTN (more afferent arteriole)

Answer 290

Malignant Hypertension: endothelium becomes injured due to high BP --\> intima swells and RBCs get trapped

Answer 291

Embolic Disease: athlerosclerotic plaques Vasculitis: from implant rejection, will sometimes see Fibrinoid Necrosis! yiipee

Answer 292

Urine will contain: muddy brown casts, may have epithelial cell casts as well. Specific Gravity may be high depending upon whether or not a chemical agent is the cause (contrast dye, IV meds)

Answer 293

Urine will contain RBCs (likely due to hemorrhage) WBCs, bacteria, nitrites, and leukocyte esterase. May contain trace protein

Answer 294

Urine will contain eosinophils and WBC casts (eosinophils, likely)

Answer 295

Nephrotic: proteinuria \> 3.5g/24hr, with NO hematuria or glucose. Fat oval bodies may be present Nephritic: proteinuria may be present but usually \< 3.5g/24hr, with hematuria, RBC casts, dysmorphic RBCs (**characteristic of glomerular injury**)

Answer 296

Uric Acid crystals would be found in the urine, as well as RBCs and WBCs. Allopurinol, febuxostat (inhibitor of xanthine oxidase)

Answer 297

occur as a result of a bacterial infection. “Coffin lid” crystals. Struvite (presumably because magnesium and sulfur - these are dense atoms that will not allow x-rays to penetrate through; unique in that they occur at an alkaline pH)

Answer 298

Indinavir crystals: needle shaped crystals with irregular borders, often arranged in a fan shape. They precipitate out of the urine in people taking the drug Indinavir --\> **nephrolithiasis**. They damage the tubular cells and provoke an inflammatory response. -navir: Protease inhibitor: Inhibit maturation of new virus by blocking protease in progeny virions

Answer 299

* Proteus mirabilis* * Klebsiella* * Ureaplasma* Urease hydrolyzes urea to release ammonia and CO2 --\> High pH (alkaline). Predisposes to struvite (ammonium magnesium phosphate) stones, particularly

Answer 300

pCO2 = (1.5 X HCO3) + 8 +/-2 or pCO2 = last 2 digits of pH

Answer 301

pCO2 = variable increase _or_ pCO2 = (0.7 X HCO3) + 20

Answer 302

Acute: HCO3 increases **1 mEq/L** for every **10 mmHg** increase pCO2 Chronic: HCO3 increases **3.5 mEq/L** for every **10mmHg** increase pCO2

Answer 303

Acute: HCO3 decreases **2 mEq/L** for every 10 mmHg decrease pCO2 Chronic: HCO3 decreases **5 mEq/L** for every 10 mmHg decrease pCO2

Answer 304

Methanol Uremia DKA Propofol **_I_**ron/ **_A_**lcoholic Ketoacidosis Lactic Acidosis Ethylene Glycol Salicylates

Answer 305

Renal tubular acidosis Diarrhea Carbonic Anhydrase Inhibitors Administration of HCL or NH4+

Answer 306

* *Role of primary cilia in PKD* – intracellular Ca and cAMP – increased proliferation/apoptosis * *For ADPKD, cystogenesis is a two-step process* – cyst initiation: earlier in PKD1 than in PKD2 – cyst expansion: faster in males than females. * Critical issues in managing PKD*: – Screening relatives at risk – Blood pressure control * *Potential treatment*: – V2R antagonists reduce cAMP levels and slow cyst growth in animals with PKD

Kidney Water Flashcards

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