1. fenestrated capillary endothelium
2. fused BM with heparan sulfate
3. epithelial layer consisting of podocyte processes
4. Charge barrier is lost in nephrotic syndrome

Cx=Ux*V/Px

Volume of plasma from which the substance is completely cleared per unit time

If Cx<GFR: net tubular reabsorption

If Cx> GFR: net tubular secretion of X

If Cx= GFR: no net secretion or reabsorption

Inulin clearance= GFR b/c it is freely filtered and is neither reabsorbed nor secreted.

GFR=C (inulin)

Creatinin clearance can  be used, althogh it slightly overestimates since is slightly secreted.

estimated using PAH clearance b/c it is both filtered and actively secreted in proximal tubule.

All PAH entering the Kidnet is excreted

ERPF= C (PAH)

RBF= RPF/(1-Hct)

ERPF underestimates true RPF by 10%

Filtration fraction= GFR/RPF; normal is 20%

Filtered load= GFR* plasma concentration

1. Afferent arteriole- constriction ↓ RPF and GFR, can be caused by NSAIDs, which ↓ dilating properties of prostaglandins on AA. FF is same
2. Efferent arteriole- constriction ↓ RPF but ↑ GFR, ↑ FF. Angiotensin II constrcts EA, and ACEi block this constriction.
3. Reabsorption= filtered (GFR * P_x) - excreted (V*Ux)
4. Secretion= excreted (V*Ux) - filtered (GFR * P_x)

glucose at a normal plasma level is completely reabsorbed in proximal tubule by Na/glu cotransport

Glucosuria is a clue to DM

At 160-200 mg/dL, glucosuria is started, with saturation at 350.

Nephron Physiology

Early Proximal Tubule:

1. Contains Brush border
2. reabsorption of glucose and AAs, Na/Cl/H20
3. PTH acts here to inhibit Na+/phosphate cotransport to ↑ Phosphate excretion
4. AT II- stimulates Na+/H+exchange → ↑Na and H20 reabsorption

Signals:

1. ↓ BP (JG cells)
2. ↓ Na+ delivery (MD cells)
3. ↑ sympathetic tone (B receptors

Erythropoetin-

• released in response o hypoxia in endothelial cells of peritubular caps

1,25 vit D-

• proximal tubule cells convert 25-OH vit D to 1,25. This acts to ↑ Ca and PO4intestinal absorption
• PTH acts on kidney to ↓ PO4 secretion and ↑ Ca reabsorption
• PTH also stimulates vit D production

Hyperkalemia (shift out of cell)

1. Insulin deficiency (↓Na/K ATPase)
2. Digitalis (↓Na/K ATPase)
3. B blockers (↓Na/K ATPase)
4. Acidosis (↑K/H exchanger)
5. Hypoerosmolarity 
6. Cell lysis

Electrolyte Disturbances

Sodium

• Low: disorientation, stupor, coma
• High: irritability, delirium, coma

Respiratory Acidosis

1. pH<7.4, pCO2>40
2. hypoventilation caused by various means
3. airway obstruction, acute lung disease, chronic disease, opioids, weakening of resp muscles

Henderson Hasselbach

Winters Formula

pH=pKa+ log (HCO3-)/(.03 pCO2)

Winters formula quantifies respiratory compensation in response to metabolic acidoses

PCO2=1.5 (HCO3-)+ 8 +/- 2

PCO2 ↑ .7 mmHg for every ↑ 1 mEQ/L HCO-3

1. Type 1 (distal)- defect in collecting tubules abillity to secrete H+→hypokalemia and risk of calcim kidney stones
2. Type 2 (proximal)- defect in proximal tubules HCO3- reabsorption →associated w hypokalemia dn hypophosphatemic ricketts
3. Type 4 (hyperkalemic)→ hypoaldosteonism or lack of collecting tubule response to aldosterone. associated with hyperkalemia and inhibition of NH3 secretion in proxima tubule→↓urine pH from less buffering capacity

1. RBC casts- GN, ischemia, or malignant HTN
2. WBC casts- tubulointestitial inflammation, acute pyelonephritis, transplant rejection
3. Granular- muddy brown casts- acute tubular necrosis
4. Waxy casts- advanced renal disease, CRF

• Nephritic. Immune complex mediated. 
• LM shows enlarged and hypercellular glomeruli, neutrophils, lumpy bumpy
• EM shows subepithelial IC humps
• IF- granular appearance due to IgG, IgM, and C3 deposition along GBM and mesangium
• frequently seen in children. peripheral and periorbital edema and dark urine. resolves spontaneously
• Frequently follows infection from impetigo, pharyngitis, or cellulitis by GAS cauding a Type II IC mediated hypersensitivity syndrome

• Nephritic
• LM and IF: crescent moon shaped consisting of fibrin and plasma proteins with parietal cells, monocytes and macrophages. poor prognosis
• Diseases:

1. Goodpastures syndrome- antibodies to GBM and alveloar BM→linear IF
2. Wegener's granulomatosis- c-ANCA
3. Microscopic polyangiitis- p-ANCA

Nephritic

Caused by SLE and MPGN

• LM- Wire looping of capillaries
• EM- subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition
• IF-granular

Nephritic syndrome

• related to Henoch-Schonlein disease:
• systemic hypersensitivity vasculitis that can be induced by many bugs/meds. sx include palpable purpura on buttocks/legs, abdominal pain, arthralgias and acute GN.

LM= mesangial proliferation

EM-mesangial IC deposits

IF- IgA based IC deposits in msangium

• often presents/flares with a URI or acute gastroenteritis

Nephritic

mutation in type IV collagen→ split BM

presents with neve disorders, ocular disorders, deafness, is X-linkes

LM- segmental sclerosis and hyalinosis

most common glomerular disease in HIV patients

LM- diffuse capillary and GM thickening

EM- 'spike and dome' appearance with subepithelial deposits

IF- granular appearance. SLE's nephrotic presentation

Caused by drugs, infections, SLE, solid tumors. 

Minimal change disease

LM- normal glomeruli

EM- foot process effacement

selective loss of albumin, not globulins, due to GBM polyanion loss

may be triggered by recent infection or immune stimulus. most common in chidren. responds to corticosteroids.

Subendothelial ICs with granular IF

Type I- tramtrack appearance due to GBM splitting caused by mesangial ingrowth

Type II EM- 'dense deposits'

Can also present as nephritic syndrome

Non enzymatic glycoslation of GBM→ ↑ permeability,thickening

NEG of eferent arterioles → ↑ GFR →mesangial expansion

LM show mesangial expansion, GBM thickening, eosinophilic nodular GN

1. Calcium (80%) preciiates at neutral pH and is radioopaque. Calcium oxalate or phosphate. hypercalcemia can precipitate. Oxalate crystals cn come from ethylene glycol or vit C abuse
2. Ammonium magnesium phosphate (15%): radiopaque, precipitates at ↑ pH,  caused b infection with proteus mirabilis, Staph, Klebsiella. Can form staghorn calculi that can be a nidus for UTIs.
3. Uric acid- radiolucent, associated with hyperuricemia (gout). preicipates at ↓ pH. seen in diseases with high cell turnover (e.g. leukemia)
4. Cystine- preicipates at ↓ pH. radioopaque. hexagonal. often secondary to cysteinuria. tx by alkanization of urine.

• Renal Cell Carcinoma- originiates in renal tubular cells. most common renal malignancy. 

1. polygonal clear cells filled with accumulated lipids and carbs
2. most common in 50-0 yo men
3. ↑ risk with smokin and obesity
4. manifests as hematuia , palpable mass, polycythemia, flank pain, fever, wt oss
5. Invades IVC and spreads hematogenenously
6. mets to lung and bone
7. A/w von Hippel-Lindau syndrome and gene deletion in chromosome 3
8. asssociated with paraneoplastic syndromes

Most comon renal malignancy of early childhood

• contains embyronic glmoerular structures
• presents with large palpable flank mass and/or heamturia
• deletion of tumor suppressor gene WTI on ch 11
• WAGR complex:

1. Wilms tumor
2. Aniridia
3. Genitourinary malformation
4. mental-motor retardation

• Most common tumor of uinary tract system (renal calyces, pelvis, ureters, bladder)
• path:papilary groth lined by transitional epithelium with mild nuclear atypia.

painless hematuria (no casts) suggests bladder cancer

associates with Pee SAC

• Phenacetin
• Smoking
• Aniline dyes
• Cyclophosphamide

• Acute: affects crtex with sparing of glomeruli and vessels. presents with fever, CVS tenderness, nausea, and vomiting
• path shows neutrophilic infiltration into renal interstitium

• Chronic: Coarse, asymettric corticomedullary scarring, blunted calyx. Tubules may contain eosinophilic casts
• WBC casts are classic
• vesicoureteral reflux is required to cause this.
• path shows lymhocytic invasion with fibrosis

Acute intersitial renal inflammation. A/w fever, rash, hematuria, and CVA tenderness

• Pyuria and Azotemia occuring 1-2 wks after drug adminstration
• Drugs: NSAIDs, penicillins, sulfonamides, rifampin, etc..
• drugs acts as haptens inducing hypersensitivity

Most comon cause of ARF in hospital. reversible but fatal if untreated. 

A/w renal ischemia, crush injury, toxins

Key finding: muddy brown casts

3 stages:

1. Initiation phase- 

• precipiated by sepsis, sx, acute MI, hemorrhage

1. maintenance phase- oliguric, last 1-3 wks.

•  risk of hyperkalemia (if peaks, Twaves and arrythmias)
• fluid overload/edema
• anion/H retention → anion gap metabolic acidosis
• ↑ serum creatinine and BUN
• highest risk of mortality

1. recovery phase-polyuric with hypotonic urine (>3L/day) as tubules are not quite 100%

•  BUN and serum creatinine fall
•  risk of hypokalemia
• risk of dehydration

Sloughing of renal papillae → gross hematuria, proteinuria. May be triggerred by a recent infection or immune status. Associated with: 

1. Diabetes mellitus
2. Acute pyelonephritis
3. Chronic phenacetin
4. Sickle cell anemia and trait

Defined as an abrpt decline in renal function and ↑ creatinine and BUN over several days

1. Prerenal azotemia: due to ↓ RBF → ↓ GFR. Na+/H20 and urea are retained in an attempt to maintain volume leading to ↑ BUN/creatinine ratio
2. Intrinsic renal: due to acute tubular necrosis or ischemia/toxins. sometimes RPGN
• patchy necrosis leads to debris obstructing tubule and and fluid backflow across necrotic tubule →↓GFR
• Urine has epithelial/granular casts
• BUN reabsorption is impaired so ↓ BUN/creatinine ratio
3. Postrenal- due to outflow obstruction

• stones, BPH, neoplasia, congenital anamolies
• develops only with bilateral obstruction

Inability to make urine and excrete nitrogenous wastes

Consequences:

1. Na/H20 retention
2. Hyperkalemia
3. Metabolic acidosis
4. Uremia- clinical syndrome marked by ↑BUN and creatinine
• nausea/anorexia
• pericarditis
• asterxis
• encephalophathy
• platelet dysfunction
5. Anemia (failure of EPO)
6. Renal osteodystrophy
7. Dyslipidemia (↑ TGs)
8. grwoth retardation/developmental delay in children

Renal osteodystrophy

• Failure of Vit D hydroxylation in kidney→ Ca wasting and Po4 retention→ 2° hyperparathyroidism
• Hyperphosphatemia also independently lowers Ca
• ↓ 1,25 vit D lowers intesintal Ca absorption
• suberiosteal thinning of bones

ADPKD

• multiple, large bilateral cysts that eventually destroy the brain parenchyma
• presents with flank pain, hematuria, HTN, urinary infection, progressive renal failure
• autsomal dominant mutation in PKD1 or PKD2
• death from chronic kidney disease or HTN (from ↑ renin)
• a/w polycystic liver disease, berry aneurysms, mitral vlve prolapse

ARPKD

• Formerly infantile polycystic kidney disease
• AR
• A/w congenital heaptic fibrosis
• concerns beyonf neonatal period are HTN, portal HTN, progressiv renal insufficiency 

1. Mech: Osmotic Diuretic, ↑ tubular fluid osmalarity → ↑urine flow
2. inhibits reabsorption of water osmotically in proximal straight tubule
3. Clinical use: Shock, drug overdose, ↑ intracranial/ocular pressure
4. Toxicity: pulmonary edema, dehydration. CI in anuria and CHF

1. Mech:

• acts at proximal tubule
• carbonic anhydrase inhibitor
• causes self limited NaHCO3 diuresis and reduction in total HCO3

1. Clinical Use: 

• Glaucoma, urinary alkanization, metabolic alkalosis, altitude sickness

1. Toxicity:

• Hyperchloremic metabolic acidosis, neuropathy, NH3 toxicity, sulfa allergy
• ACIDazolamide causes ACIDosis

• Mech:
• sulfonamide loop diuretic
• inhibits (Na/K/2CL) cotransport system of thick ascending loop of Henle
• abolishes hypertonicity of medulla, lowering urine concentrating ability
• stimulates PGE release (vasodilates afferent arteriole)
• effect inhibited by NSAIDs
• ↑ Ca excretion
• Clinical Use:
• edamotous states (CHF, cirrhosis, nephrotic,  pulmonary edema), HTN, hypercalcemia
• Toxicity (OH DANG!)
• Ototoxicity
• Hypokalemia
• Dehydration
• Allergy
• Nephritis (intersitial)
• Gout
• LDs can cause alkalemia through several mechs:
• volume contraction→↑ATII→↑Na/H exchnage in PT→↑HCO3- (contraction alkalosis)
• K+ loss leads to K+ exiting all cells in exchange for H+ entering cells
• H+ is exchanged for Na instead of K+ in CCT, causing alklaosis and paradoxical aciduria.

1. Mech:

• phenoxyacetic acid deravitive. same action as furosemide

1. Clinical use:used in patients allergic to sulfas
2. Toxicity: can be used to treat acute gout

1. Mech:
• Thiazide diuretic inhibits NaCl reabsorption in early distal tubule, reducing diluting capacity of the nephron. 
• ↓ Ca excretion
2. Clinical use
• HTN, CHF, idiopathic hypercaciuria, nephrogenic diabetes insipidus
3. Toxicity
• Hypokalemic metabolic alkalosis, hyponatremia 
• hyperGLUC:
• hyperGlycemia
• hyperLipidemia
• hyperUrecemia
• hyperCalcemia
• sulfa allergy
4. Thiazides can cause alkalemia through several mechs:
• volume contraction→↑ATII→↑Na/H exchnage in PT→↑HCO3- (contraction alkalosis)
• K+ loss leads to K+ exiting all cells in exchange for H+ entering cells
• H+ is exchanged for Na instead of K+ in CCT, causing alklaosis and paradoxical aciduria.

1. Examples are Spironolactone, Traimateine, Amiloride (the K+ STAys)
2. Mech:
• spironlactone is a competitive aldosterone receptor antagonist in CCT
• Triamterine/amiloride block Na channels in CCT
3. Clinical use
• Hyperaldosteronism, K+ depletion, CHF
4. Toxicity

• Hyperkalemia (possible arrhythmias)
• endocrine effects from aldosterone antagonism (gynecomastia, antiandrogen effects)

1. Potter's Syndrome

Caused by any etiology leading to oligo or anhydramnios for fetus.

An example would be bilatera renal agenesis.

Sings of potters syndrome include:

1. clubfeet
2. classic facies
3. pulmonary hypolasia

• Can be caused by drugs, such as lithium which antagonizes lithium
• Ability of Kidney to concentrate urine is compromised, as ADH cannot act on CCT.

Can occur in men with membranous glomerulopathy. Left sided indicates obstruction of left renal vein by thrombus or tumor.

Thrombus can occur in nephrotic syndrome (e.g.MG) which leads to loss of AT III and hypercoaguable state.

The triad of acute abdominal flank pain (renal colic), hematuria, and left sided varicocele