1. Duodenum (2nd, 33rd, 4th parts)

2. Descending colon

3. Ascending colon

4. Kidneys and Ureters

5. Pancreas

6. Aorta

7. IVC

8. Adrenal glands and rectum

TBW-ECF=ICF

ECF-PV=interstitial volume. 

60-40-20 rule (% of body weight):

60% total body water

40% ICF

20%ECF

Plasma volume measured by radiolabeled albumin

Extracellular volume measured by inulin. 

Cx=UxV/Px=Volume of plasma from which the substance is cleared completely per unit time.

If Cx<GFR then ther eis net tubular reabsorption of X

If Cx>GFR then there is net tubular secretion of X

If Cx=GFR then ther eis no net secretion or reabsorption. 

Responsible for filtration of plasma according to size and net charge.

Composed of: 

1. Fenestrated capillary endothelium (size barrier)

2. Fused basmenet membrane with heparin sulfate (negative charge barrier)

3. Epitehlial layer consisting of podocyte foot processes. 

Charge barrier is lost in nephrotic syndrome, resulting in albuminuria, hypoproteinemia, generalized edema and hyperlipidemia.

Inulin can be used to calculate GFR because is is freely filtered and neither reabsorbed nor secreted.

Creatinine clearance is an approximate measure of GFR

GFR =Uinulin xV/Pinulin=Cinulin=Kf[(Pgc-Pbs)-(pigc-pibs)] (gc=comerular capillary;bs=bowman's space.) pibs normally equals zero.

ERPF can be estimaed using PAH because it is both filtered and actively secreted into the proximal tubule. All PAH entering the kidney is excreted.

ERPF=UpahxV/Ppah=Cpah

RBF-RPF/(1-Hct)

ERPF underestimates true RPF by approximately 10%

FF/GFR/RPF

NSAIDs (Prostaglandins dilate afferent arteriole (Increase RPF, increase GFR, so FF remains constant)

 ACE inhibitors (angiotensin II preferentially constricts efferent arteriole (decrease RPF, increase GFR, so FF increases))

Changes in Renal function

1. Afferent arteriole constriction

2. Efferent arteriole constriction

3. Increase plasma protein concentration

4. Decrease plasma protein concentration

5. Constriction of Ureter

1. Decrease RPF, Decrease GFR, NC FF

2. Decrease RPF, Increase GFR, INcrease FF

3. NC RPF, Decrease GFR, Decrease FF

4. NC RPF, Increase GFR, Increase FF

5. NC RPF, Decrease GFR, Decrease FF

Given urine flow rate, urine osmolarity and plasma osmolarity, calculate free water clearance

C(H20)=V-Cosm

V=urine flow rate; Cosm=UosmV/Posm

Glucose at a normal level is completely reabsorbed in proximal tubule. At plasma glucose of 200 mg/dL, glucosuria begins (threshold). At 350 mg/dL, transport mechanism is saturated (Tm)

Glucosuria is an important clinical clue to diabetes mellitus

A. Early proximal convoluted tubule-"workhorse of the nephron." Reabsorbs all the glucose and amino acids and most bicarbonate, sodium and water. Secretes ammonia, which acts as a buffer for secreted H+.

B. Thin descending loop of Henle--passively reabsorbs water via medullary hypertonicity (impermeable to sodium).

C. Thick ascending loop of Henle--actively reabsorbs Na+, K+, Cl- and indirectly induces the reabsorption of Mg and Ca. Impermeable to H2O. 

D. Early distal convoluted tubbule--actively reabsorbs Na, Cl. Reabsorption ofCa is under control of PTH. 

E. Collecting tubules-reabsorb Na in exchange for secreting K or H (regulateed by aldosterone). Reabsorption of water is regulated by ADH (vasopressin). Oxmolarity of medulla can reach 1200 mOsm

Mechanism: Released by kidneys upon sensing decrease BP and cleaves nagiotensiongen to angiotensin I (a decapeptide). Angiotensin I is then cleaved by ngiotensin-cnoverting enzyme (ACE), primarily in the lung capillaries and elsewhere, to angiotensin II (an octapeptide).

Actions of Angiotensin II

1. Potent vasoconstriction

2. Release of aldosterone from adrenal cortex

3. Release of ADH from posterior pituitary

4. Stimulates hypothalamus leads to increased thirst

Overall, angiotensin II serves to increase intravascular volume and increasae BP. 

ANP released from atria may act as check on renin angiotensin system. 

JGA-JG cells (modified smooth muscle of afferent arteriole) and macula densa (Na sensor part of distl convoluted tubule). JG cells secrete renin (leading to increase angiotensin II And aldosterone levles) in response ot decreased renal bp, decreased Na delivery to distal tubule and increaase sympathetic tone.

JGA defends glomerular filtration rate via the renin-angiotensin system. Juxta=close bby. 

1. Endothelial cells of peritubular capillaries secrete erythropoietin in response to hypoxia

2. Conversion of 25-OH vitamin D to 1,25 OH2 vitamin D by 1alpha hydroxylase which is activated by PTH

3. JG cells secrete renin in response to derease renal arterial presure and increase renal sympathetic discharge (Beta 1 effect)

4. Secretion of protaglandins that vasodilate the afferent arterioles to increase GFR. 

NSAIDs can cause acute renal failure in high vasoconstrictive states by inhibiting the renal production of prostaglandins which keep afferent arterioles vasodilated to maintain GFR

1. Aldosterone: secreted in response to decreased blood volume (via AT II) and increased plasma [K]. Causes increased Na reabsorption, increased k+ secretion, increased H+ secretion. 

2. Angiotensin II (AT II)

Causes efferetn arteriole constriction leads to increased GFR leadds to increased Na and HCO3 reabsorption

3. Vasopressin /ADH

Secreted in response to increased plasma osmolarity and decreased blood volume. Binds to receptors on principal cells causing increased number onf water channels and increased H2O reabsorption. 

4. Parathyroid hormone (PTH) 

Secreted in response to decreased plasma [Ca] Causes increased [Ca] reabsorption (DCT) Decreased PO4 reabsorption (PCT), 1,25 (OH)3 vitamin D produciton leaads to increased Ca and PO4 reabsorption.

5. Atrail natriuertic factor (ANF) 

Secreted in response to increased atrial pressure, causes increased GFR and increased NA excretion

Metabolic acidosis

Metabolic alkalosis

Metabolic acidosis: Decreased pH, Pco2, HCO3

 Compensatory response Hyperventilation

Metabolic alkalosis: Increased pH, Pco2, HCO3

Compensatory response Hypoventilation

Respiratory acidosis

Respiratory alkalosis

Respiratory acidosis: decreased pH, increased Pco2, increased HCO3

Compensatory response: Renal HCO3 reabsorption

Respiratory alkalosis: increased pH,decreased Pco2, decreased HCO3

Compensatory response: Renal HCO3 secretion. 

Respiraotry acidosis

Pco2>40 mmHg, pH<7.4

Hypoventilation causes:

1. Airway obstruciton

2. Acute lung disease

3. Chronic lung disease

4. Opiods, narcotics, sedatives

5. WEakening of repiratory muscles

Metabolic acidosis with compensation

pH<7.4, Pco2<40mmHg

Check anion gap=  Na-(Cl+HCO3)

Increased anion gap

MUD PILES

Methanol, Uremia, Diabetic ketoacidosis, Paraldehyde or Phenformin, Iron tablets or INH, Lactic acidosis Ethylene glycol, Salycilates

Normal anion gap (8-12 mEq/L)

1. Diarrhea

2. Glue sniffing

3. Renal tubular acidosis

4. Hyperchloremia

Respiratory alkalosis

pH>7.4, Pco2<40 mmHg

Metabolic alkalosis with compensation

pH>7.4, PCo2 >40 mmHg

Respiratory alkalosis:

Hyperventilation

Aspirin ingestion (early)

Metabolic Alkalosis:

Vomiting

Diuretic use

Antacid use

Hyperaldosteronism

Metabolic acidosis: Winter's formula: Pco2=1.5 HCO3-8+-2

Metabolic alkalosis: Pco2 increases .7 mmHg for every increse 1 mEq/L HCO3

Respiatory acidosis: Acute--Increase 1 mEq/L HCO3 froo every 10  mmHg increse in PCO2

Chronic--Increase 3.5 mEq/L HCO3 for every 10 mmHg increase PCO2

Respiratory alkalosis: Acute--decrease 2 mEq/L HCO3 for every decrease 10 mmHg Pco2

Chronic--dddecrease 5 mEq/L HCO3 for every 10 mmHg decrease Pco2. 

Bilateral renal agenesis-->oligohydramnios-->limb deformities, facial deformities, pulmonary hypoplasia. Caused by malformation of uteric bud.

Babies with Potter's can't Pee in utero

Casts indicate that hematuria/pyuria is of renal origin.

Bladder cancer-->RBCs

Acute cystitis-->WBCs

RBC casts-glomerullar inflammation (nephritic syndromes), ischemia, or malignant hypertension.

WBC casts-tubulointerstitial disease, acute pyelonephritis, glomerular disorders.

Granular casts-acute tubular necrosis

Waxy casts-advanced renal disease/CRF

Hyaline casts-nonspecific

1. Acute poststreptococcal glomerulonephritis--LM: glomeruli enlarged and hypercellular, neutrophils "lumpy bumpy." EM: subepithelial humps. IF: granular pattern. (Most frequently seen in children. PEripheral and periorbital edema. Resolves spontaneously.)

2. Rapidly progressive (Crescentic) glomerulonephritis--LM and IF: crescent moon shape. Rapid course to renal failure from one of many causes.

3. Goodpasture syndrome (type II hypersensitivity)--IF: linear pattern, anti-GBM antibodies.  (Hemoptysis, hematuria)

4. Membraneoproliferative glomerulonephritis--EM: subendothelial humps, "tram track." (Slowly progressees to renal failiure

5. IgA nephropathy (Berger's disease--IF and EM: mesangial deposits of IgA. (Milddisease. Often postinfectious. 

6. Alport's syndrome--split basement memrbane (collagen IV mutation. Nerve deafness and ocular disorders.)

NephrOtic syndrome--massivie proteinuria, hypoalbuminemia, peripheral and periorbidal edema, hyperlipidemia.

O=prOteinura

1. Membranous glomoerulonephritis-LM: diffuse capillary and basement membrane thickening. IF: granular patern. EM: "spike and dome"  (A common cause fo adult nephrotic syndrome.

2. Minimal change disease (lipoid nephprosis)--LM: normal glomeruli. EM: foot process effacemenet (Most common cause of childhood nephrotic syndrome. Responds well to steroids.)

3. Focal segmental glomerular slecrosis--LM: segmental sclerosis and hyalinosis (More severe edisease in HIV patietns).

4. Diabetic nephropathy--LM: KimmelstielWilson "wire loop" lesions, basement membrane thickening. 

5. SLE (systemic lupus erythmatosus) (5 patterns of renal involvement)--LM: In membranous glomerulonephritis pattern, wire loop lesion with subendothelial deposits. 

Kidney stones

Can lead to severe complications like hydronephrosis and pyelonephritis. 4 types.

1. Calcium-most common kidney stones (75-85%). Calcium oxalate, calcium phosphate or both. Conditions that cause hypercalcemia (cancer, increased PTH, increased vitamin D, milk-alkali syndrome) can leaed to hypercalcuria and stones. Tend to recur. Radiopaque.

2. Ammonium magnesium phosphate (struvite)--2nd most common kidney stone. Caused by infection with urease-postiive bugs (Proteus vulgaris, Staphylococcus, Klebsiella). Can form staghorn calculi that can be nidus for UTIs. Radiopaque. 

3. Uric acid-strong associations with hyperuricemia (eg gout). Often seen as result of diseases with increased cell turnover like leukemia and myeloprolifferative disorders. Radiolucent

4. Cystine-most often secondary to cytinuria. Radiolucent.

Most common renal malignancy. Most common in men ages 50-70. Increased incidence with smoking and obesity. Associated with Hippel-Lindau adn gene deletion in chromosome 3. Originates in renal tubule cells-->polygonal clear cells.

Manifests clincially with hematuria, palpable mass, seocndayr polycythemia, flank pain, feer and weight loss.

Invades IVC And spreads hematogenously.

Associated with paraneoplastic sydromes (ectopic EPO, ACTH, PTHrP and prolactin)

Most common renal malignancy of early childhood (ages 2-4). Presents with huge, palpable flank mass, hemihypertrophy. Deletion fo tumor suppression gene WT1 on chromosome 11. Can be part of WAGR complex:

1. Wilms' tumor

2. Aniridia

3. Genitourinary malformation

4. Mental-motor Retardation

Most common tumor of urinary tract system (can occur in renal calyces, renal pelvis, ureters and bladder). Painless hematuria is suggestive of bladder cancer. Associated problems in your Pee SAC:

1. Phenacetin

2. Smoking

3. Aniline dyes

4. Cyclophosphamide

Acute: Affects cortex with relative sparign of glomeruli/vessels. White cell casts in urine are pathognomic. PResents with fevere, CVA tenderness.

Chronic: Coarse, asaymmetric corticomedullary scarring. Tubules can contain eosinophilic casts (thyroidization of kidney)

Associated with:

1. Diabetes mellitus

2. Acute pyelonephritis

3. Chronic phenacetin use

Abrupt decline in renal function with increase creatinine and increase BUN over a period of several days.

1. Prerenal azotemia-decreased RBF (eg hypotension)-->Decrease GFR. Na/H20 retained by kidney.

2. Intrinsic renal--generally due to actue tubular necrosis or ischemia/toxins. Patchy necrosis leads to debris obstructing tubule and fluid backflow across necrotic tubule leads to decrease GFR. Urine has epithelial/granular casts. 

3. Postrenal--outflow obstruction (Stones, BHP, neoplasia). Develops only with bilateral obstructiont.

Consequences of renal failure: failure to make urine and excrete nitrogenous wastes.

Uremia--clinical syndrome marked by increase BUN and increase creatinine and associated symptoms. 

1. Anemai (failure of erythropoietan production)

2. Renal osteodystrophy (failure of active vitamin D produciton)

3. Hyperkalemia, which can lead to cardia arrhythmias

4. Metabolic acidosis due to decrease acid secretion and decrease generation of HCO3. 

5. Uremic encephalopathy

6. Sodium and H2O excess-->CHF and pulmonary edema.

7. Chronic pyelonephritis

8. Hypertension

2 forms of renal failure--acute renal failure (often due to hypoxia) and chronic fenal failure (due to hypertension and diabetes. 

1. Na: Low (disorientation, stupor, coma); High (Neurolgoic, irritability, delirium, coma)

2. Cl: Low (secondary to metabolic alkalosis); Hgih secondary to non-anion gap acidosis

3. K: Low (U waves on ECG, flattened T waves, arrhythmias, paralysis; High (Peaked T waves, arrhythmias

4. Ca: Low (Tetany, neuromusuclar irritability); High (delirium, renal stones, abdominal pain)

5. Mg: Low (neuromuscular iritability, arrhythmias); High (delirium, decreased DTR, cardiomulmonary arrest.

6. PO4: Low (low-mineral ion products causes bone loss); High (high mineral ion products cause metastatic cacificaiton, renal stones

1. Acetazolamide (PCT)

2. Osmotic agents like mannitol (PCT, DLH, Collecting duct)

3. Loop agents like furosemide  (Thick AL)

4. Thiazides (DCT)

5. Potassium sparing (DCT/Collecting duct)

6. ADH antagonists (colecting duct)

Mechanism: Osmotic diuretic, increase tubular fluid osmolarity, producing increased urine flow.

Clinical use: Shock, druug overdose, decrease intracranial/intraocular pressure

Toxicity: Pulmonary edema, dehydration. Contraindicated in anuria, CHF

Mechanism: Carbonic anhydrase inhibitor. Cuases self-limited NaHCO3 diuresis and reduciton in total-body HCO3 stores. Acts at the proximal convoluted tubule.

 Clinical use: Glaucoma, urinary alkanization, metabolic alkalosis, altitude sickness.

Toxicity: Hyperchloremic metabolic acidosis, neuropathy, NH3 toxicity, sulfa allergy. 

ACIDazolamide causes ACIDosis

Mechanism: Sulffonamide loop diuretic. Inhibits cotransport systetm (Na, K, 2Cl) of thick ascending limb of loop of Henle. Abolishes hypertonicity of medulla,preventing concentration fo urine. INcreases Ca excretion. Loops Lose calcium.

Clinical use: Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, hypercalcemia. 

Toxicity: Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout

OH DANG

Mechanism: Phenoxyacetic acid derivative (NOT a sulfonamide). Essentially same action as furosemide.

Clinical use: Diuresis in patietns allergic to sulfa drugs.

Toxicity: Similar to furosemide; can be used in hyperuricemia, acute gout (never used to treat gout). 

Mechanism: Thiazide diuretic. Inhibits NaCl reabsorption in early distal tubule, reducing dilutin capacity of the nephron. Decrease Ca excretion.

Clinical use: Hypertension, CHF, idiopathic hypercalciuria, nephrogenic diabetes insipidus.

Toxicity: Hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, and hyperCalcemia. Sulfa allergy. 

HyperGLUC

Spironolactone, Triamterene, Amiloride, eplereone

The K STAys

Mechanism: Spronoloactone isa competitive aldosterone receptor antagonist in the cortical collectingi tubule. Riamterene and amiloride act at the same part of the tubule by blocking Na channels in the CCT

Clinical use: Hyperaldosteronism, K depletion, CHF

Toxicity: Hyperkalemia, endocrine effects (spironolactone causes gynecomastia, antiandrogen effects).

1. Urine NaCl: increases (All diuretics--carbonic anhydrase inhibitors, loop diuretics, thiazides, K sparing diuretics).

2. Urine K: increases (All except K sparing diuretics)

3. Blood pH: decreases (acidosis)--carbonic anhydrase inhibitors, K sparing diuretics; Increases (alkalosis) loop diuretics, thiazides.

4. Urine Ca: increase loop diuretics, decrease thiazides

Captopril, enalapril, lisinopril

Mechanism: Inhibits angiotensin convertinge nzyme, reducing levels of angiotensin II Iand preventing inactivation of bradykinin a potent vasodilator. Renin release is increased due to loss of feebdack inhibition. 

Lsartan is an angiotensin II receptor antagonist. It is NOT an ACE inhibitor and does NOT cause cough. 

Clinical use: Hypertension, CHF, diabetic renal disease

Toxicity: Cough, Angioedema, Proteinuria, Taste changes, hypOtension, Pregnancy probelms (fetal renal damage), Rash, Increased renin, Lower angiotensin II. Also hyperkalemia. 

CAPTOPRIL