PATHOLOGY: F-find DR. S-sanjay GUPTA  = FDRSGUPTA --> F-failure of kidney, D-DI & SIADH, R-RTA, S-stone, G-glomerular disease, U-ureteral reflux, P-PKD, T-tubulointerstitial diseases, T-tumor, A-acid base and electrolytes disorder.


·       DI




NEPHRITIC SYNDROMES: TYPES: RAW PIG --> R-RPGN (rapidly progressive glomerular nephritis), A-alport’s syndrome, W-WG (Wegener’s granulomatosus), P-PSGN (post-streptococcal glomerular nephritis), I-IgA nephropathy, G-GP (Goodpasture’s syndrome).
v  R _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________

v  W _______________, _______________, _______________, _______________, _______________

v  P _______________, _______________, _______________, _______________, _______________

v  I _______________, _______________, _______________, _______________, _______________

v  G _______________, _______________, _______________, _______________, _______________

NEPHROTIC SYNDROME: TYPES OF NEPHROTIC SYNDROME:  Nephrotic syndrome may either be the result of a disease limited to the kidney (primary), or a condition that affects the kidney and other parts of the body (secondary). A-all MD’s S-skip F-foreplay = AMDSFP --> A-amylodosis, M-MCD (minimal change disease), M-membranous nephropathy, M-membranoproliferative glomerulonephritis, D-diabetic nephropathy, S-SLE-induced, S-sarcoidosis, F-FSGS (focal segmental glomerulosclerosis). 
v  A _______________, _______________, _______________, _______________, _______________

v  M _______________, _______________, _______________, _______________, _______________

v  D _______________, _______________, _______________, _______________, _______________

v  S _______________, _______________, _______________, _______________, _______________

v  F _______________, _______________, _______________, _______________, _______________

·       TUBULAR AND INTERSTITIAL DISEASE:  RAT --> R-renal papillary necrosis, A-ATN (acute tubular necrosis), T-tubulointerstitial nephritis.

o   R _______________, _______________, _______________, _______________, _______________

o   A _______________, _______________, _______________, _______________, _______________

o   T _______________, _______________, _______________, _______________, _______________


·       TUMORS:  Benign tumor: Oncocytoma and angiomyolipoma.  Malignant tumor:  Wilm’s tumor and RCC (renal cell carcinoma).

·       ACID-BASE: 

·       ELECTROLYTES DISORDER:  Intracellular ions (KCOM --> K-k+, C-ca2+, O-organic anion, M-mg2+).  Extracellular ions (Na+, Cl-, HCO3-).

HYPERCALCEMIA (normal 9-10.5 mEq/L):
o   HYPOCALCEMIA:  Total calcium < 9 mEq/L.   

o   HYPERKALEMIA:   Normal range 3.5-5 mEq/L.


o   HYPOMAGNESEMIA:   Normal 1.7-2.3 mEq/L.

o   HYPERNATREMIA:  Normal serum sodium 135-148 mEq/L.

o   HYPONATREMIA:  < 135 mEq/L.

o   HYPOPHOSPHATEMIA (< 2.7 mg/dL): 


















PATHOLOGY: Prostatitis, BPH, and Prostate cancer.




EMBRYOLOGY: The intermediate mesoderm (between paraxial and lateral plate mesoderm) forms a longitudinal elevation along the dorsal body wall, called the urogenital ridge.   A portion of the urogenital ridege, the nephrogenic cord, successively forms the pronephros (day 22), mesonephros (day 35) and metanephros (> 40 days). 

·       Pronephros:   Form at the cranial end by the arrangement of epithelial cells into a series of tubules called nephrotomes and join laterally with the pronephric duct.  It regresses completely

Diagram shows the sequential development and degeneration of the pronephros and mesonephros, and the induction of the ureteric bud and metanephric mesenchyme during kidney development in mammals.

By Ashley Sawle - Own work, CC BY-SA 3.0,

·       MesonephrosAs the pronephric duct grows caudally, it induces intermediate mesoderm in the thoracolumbar area to become epithelial tubules called mesonephric tubules. Arterioles form off the dorsal aorta connects to these mesonephric tubules to form primitive glomeruli.  Thus, an ultrafiltrate can pass from the glomeruli into the mesonephric duct.  This filtrate flows through the mesonephric tubule and is drained into the continuation of the pronephric duct, now called the mesonephric duct or Wolffian duct.

Reconstruction of a human embryo of 17 mm. (After Mall.)

By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below) Gray's Anatomy, Plate 986, Public Domain,

·       Metanephros:  Forms when the ureteric bud (aka ureteric duct), an outgrowth of the mesonephric duct, grows into the sacral intermediate mesoderm.  The ureteric bud branches multiple times and forms renal pelvis --> major calices --> minor calices --> CDs (collecting ducts).  The terminal branches of the ureteric duct (the collecting tubules) interact with the intermediate sacral mesoderm (metaneprogenic basterma) to form nephrons.  Signals released from the ureteric bud induce the differentiation of the metanephrogenic blastema into the renal tubules. As the renal tubules grow, they come into contact and join with connecting tubules of the collecting duct system, forming a continuous passage for flow from the renal tubule to the collecting duct.

·       The permanent kidney ascends during development from the sacral region to its adult anatomical location at T12-L3.


·       GENERALDimension: 10 cm long, 5.5 cm in width and about 3 cm thick.  Weight: 150 grams. Hilum: On the medial aspect of each kidney, it admits the renal artery, renal vein, nerves, and ureter.  The kidney has a loose connective tissue/fibrous capsule. The outer portion of the kidney is called the renal cortex.  Deep to the cortex lies the renal medulla, which is divided into 10-20 renal pyramids. The tip of each pyramid (called a papilla) empties into a calyx, and the calices empty into the renal pelvis. The pelvis transmits urine to the urinary bladder via the ureter.

Surface projections of the organs of the trunk, showing kidneys at the level of T12 to L3.

By Mikael Häggström - All included images are in public domain. See Template:Human body diagrams for individual details.ReferencesSpinal vertebrae levels:Located at middle of frontal face of spinal vertebrae according to reference the image :File:Gray 111 - Vertebral column.png when pasted into image to superiorly fit the surface bulges of the clavicular bones and inferiorly fit the surface bulges of the anterior iliac spine.Gross overview of organ locations:Plate 260B - Regions and Planes of Adbomen. From: The Interactive Atlas of Human Anatomy Version 3.0 (CD-ROM). Authors: Frank H. Netter and Carlos A. G. Machado. Published by Saunders, October 1, 2002. ISBN-10: 1929007140. ISBN-13: 978-1929007141.Fig 139 from The SPENCER SYSTEM. SEVENTEENTH EDITIONPlate 1034 from Gray's AnatomyLocations of specific organs:The following vertebral levels are generally given by the middle of the vertebral body.Bålens ytanatomy (Superficial anatomy of the trunk). Anca Dragomir, Mats Hjortberg and Godfried M. Romans.

Anatomical dissections.

3D-rendered computed tomography, showing renal arteries and veins.

CT scan of the kidneys. Left: cross section at upper abdomen level – the liver is seen on the left side of scan (right side of body). Center: longitudinal section though the center of the kidneys – the liver partially covers the right kidney. Right: transverse section through the left kidney.

By RGshredfox - It is taken from a radiological CT scan of my abdomen, it is in effect a picture of me., CC BY-SA 3.0,


ARTERIAL SUPPLY:  The 2 renal arteries are branches from the abdominal aorta. Due to the position of the aorta, the right renal artery is normally longer than the left renal artery.
Ø  The right passes behind the IVC, the right renal vein, the head of the pancreas, and the descending part of the duodenum.

Ø  The left is somewhat higher than the right; it lies behind the left renal vein, the body of the pancreas and the lienal vein, and is crossed by the IMA.

o   VENOUS DRAINAGE:  Due to the position of the IVC, the left renal vein is longer than the right.

Ø  The right renal vein drains directly into the IVC.

Ø  The left renal vein often receives the following veins (left inferior phrenic vein, left suprarenal vein, left gonadal vein (left testicular vein in males, left ovarian vein in females), left 2nd lumbar vein.

Kidney Anatomy.

Diagram of kidney, with arcuate arteries being the red-colored vessels among the "Arcuate blood vessels" labeled at top right.

By OpenStax College - Anatomy & Physiology, Connexions Web site., Jun 19, 2013., CC BY 3.0,


o   FLOW OF THE ULTRAFILTRATEThe functional component of the kidney is a nephron.  Each nephron is composed of an initial filtering component (the “renal corpuscle”) and a tubule specialized for reabsorption and secretion (the “renal tubule”). After passing the tubule, the filtrate continues to the collecting duct system.

Ø  THE RENAL CORPUSCLE (aka Malphigian corpuscle):  Composed of a glomerulus and Bowman's capsule

GLOMERULUS:  The capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. The glomerular blood pressure provides the driving force for water and solutes (~ 1/5 of all plasma passing through the kidney) to be filtered out of the blood and into the space made by Bowman's capsule. The remainder of the blood passes into the efferent arteriole. It then moves into the vasa recta, which are collecting capillaries intertwined with the convoluted tubules through the interstitial space, where reabsorbed substances will also enter. This then combines with efferent venules from other nephrons into the renal vein, and rejoins the main bloodstream.

BOWMAN’S CAPSULE: Surrounds the glomerulus and is composed of a visceral inner layer and a parietal outer layer, both formed by simple squamous epithelial cells.  Fluids from blood in the glomerulus are collected in the Bowman's capsule and further processed along the nephron to form urine. This process is known as ultrafiltration.

Diagram of a long juxtamedullary nephron (left) and a short cortical nephron (right). All parts of the nephron are labelled except the (gray) connecting tubule located after the (dark red) distal convoluted tubule and before the large (gray) collecting duct (mislabeled collection duct).

By Artwork by Holly Fischer - - Urinary Tract Slide 20, 26, CC BY 3.0,

Schematic diagram of the nephron (yellow), relevant circulation (red/blue), and the four methods of altering the filtrate.

Schematic diagram of the nephron (yellow), relevant circulation (red/blue), and the four methods of altering the filtrate.

(a) Diagram of the juxtaglomerular apparatus: it has specialized cells working as a unit which monitor the sodiujuxtaglomerular apparatus: it has three types of specm content of the fluid in the distal convoluted tubule (not labelled - it's the tubule on the left) and adjust the glomerular filtration rate and the rate of renin release. (b) Micrograph showing the glomerulus and surrounding structures.

By OpenStax College - Anatomy & Physiology, Connexions Web site., Jun 19, 2013., CC BY 3.0,

Glomerulus. (Bowman's capsule not labeled, but visible at top.)

By Henry Vandyke Carter - This is a retouched picture, which means that it has been digitally altered from its original version. Modifications: vectorization (CorelDraw). The original can be viewed here: Gray1130.png. Modifications made by Mysid., Public Domain,

Ø  THE RENAL TUBULE: Consist of the PCT (proximal convoluted tubules), the LOH (loop of Henle), and the DCT (distal convoluted tubule).


Proximal tubule cell showing pumps involved in acid base balance, left is the lumen of tubule

LOHDivided into 1) Descending LOH 2) Thin ascending LOH 3) Thick ascending LOH

Ø  THE CD (collecting duct):  Accounts for 4-5% of the kidney's reabsorption of Na+ and 5% of water.  It is impermeable to water without the presence of ADH.  When ADH is present, aquaporins allow for the reabsorption of this water, thereby inhibiting diuresis.  Contains two cell types, intercalated cells and principal cells.

1.     INTERCALATED CELLS:  Play important roles in the kidney's response to acidosis and alkalosis. Damage to the α-intercalated cell's ability to secrete acid can result in distal renal tubular acidosis (RTA type I, classical RTA).

Image depicting an α intercalated cell

By Rswarbrick - Own work, based on's Alpha_Intercalated_Cell_Cartoon.jpg., CC BY 3.0,

Diagram outlining movement of ions in nephron, with the collecting ducts on the right.

2.     PRINCIPAL CELLS:  Control Na+ and K+ balance via channels located on the cell's apical membrane. Aldosterone determines the sodium channels transport ions.

Scheme of filtration barrier (blood-urine) in the kidney. A. The endothelial cells of the glomerulus; 1. pore (fenestra).
B. Glomerular basement membrane: 1. lamina rara interna 2. lamina densa 3. lamina rara externa
C. Podocytes: 1. enzymatic and structural proteins 2. filtration slit 3. diaphragma

By M•Komorniczak -talk-, polish wikipedist.Illustration by : Michał KomorniczakThis file has been released into the Creative Commons 3.0. 

PHYSIOLOGY:  The kidney is one of the major organs involved in whole-body homeostasis. Among its homeostatic functions are

·       Excretion of waste:  Urea (from protein catabolism) and uric acid (from nucleic acid metabolism) and water.

·       Acid-base balance:  The kidneys regulate the pH, by eliminating H+ ions.  Thus, the blood plasma is maintained by the kidney at a slightly alkaline pH of 7.4. Urine, on the other hand, is acidic at pH 5.

·       Blood pressure:  Control via the Renin-angiotensin system --> Low blood pressure is sensed by the JGA (juxtaglomerular apparatus), which secrete a proteolytic enzyme called Renin.  Renin converts angiotensinogen to angiotensin I (10 amino acids), which in turn, is converted to Angiotensin II (8 amino acids) by ACE (angiotensin-converting enzyme) in the lung capillaries.  Angiotension II stimulates the secretion of Aldosterone by the adrenal cortex, which then increases the reabsorption of Na+ ions in the DCT.  The increased Na+ reabsoprtion causes an increase in the volume of water that is reabsorbed from the tubule, which increases the volume of blood and raises the blood pressure.

o   JGA:  Named for its proximity to the glomerulus: it is found between the vascular pole of the renal corpuscle and the returning DCT of the same nephron. This location is critical to its function in regulating RBF (renal blood flow) and GFR (glomerular filtration rate). The three microscopic components of the apparatus are the juxtaglomerular cells, macula densa, and extraglomerular mesangial cells.

An acid base nomogram for human plasma, showing the effects on the plasma pH when carbonic acid (partial pressure of carbondioxide) or bicarbonate occur in excess or are deficient in the plasma

RAAS schematic

By Soupvector - Own work, CC BY-SA 4.0,

Renal corpuscle:The structure on the left in blue and pink is the renal corpuscle. The structure on the right is the renal tubule. The blue structure (A) is the Bowman's capsule (2 and 3). The pink structure is the glomerulus with its capillaries. At the left, blood flows from the afferent arteriole (9), through the capillaries (10), and out the efferent arteriole (11). The mesangium is the pink structure inside the glomerulus between the capillaries (5a) and extending outside the glomerulus (5b). The green structure (6) represents granular cells (juxtaglomerular cells). Macula densa is #7.

Plasma volume: A rise in plasma osmolality is detected by the hypothalamus, which then secrete ADH from its nerve terminal in the posterior pituitary gland. ADH stimulates water reabsorption by the kidney, thus bringing the plasma osmolality to its normal levels.

Hormone secretion: The kidneys secrete EPO (erythropoietin), urodilatin, renin, and synthesize the active form of vitamin D (calcitriol).

PATHOLOGY: F-find DR. S-sanjay GUPTA  = FDRSGUPTA --> F-failure of kidney, D-DI & SIADH, R-RTA, S-stone, G-glomerular disease, U-ureteral reflux, P-PKD, T-tubulointerstitial diseases, T-tumor, A-acid base and electrolytes disorder.

·       F _______________, _______________, _______________, _______________, _______________

·       D _______________, _______________, _______________, _______________, _______________

·       R _______________, _______________, _______________, _______________, _______________

·       S _______________, _______________, _______________, _______________, _______________

·       G _______________, _______________, _______________, _______________, _______________

·       U _______________, _______________, _______________, _______________, _______________

·       P _______________, _______________, _______________, _______________, _______________

·       T _______________, _______________, _______________, _______________, _______________

·       A _______________, _______________, _______________, _______________, _______________

·       FAILURE OF KIDNEY (RENAL FAILURE):  A situation in which the kidneys fail to function adequately. Biochemically, it is typically detected by an elevated serum creatinine. In physiology, it is described as a decrease in the GFR.

CLASSIFICATION:  Divided into 2 categories depends on the trend in the serum creatinine: 1) ARF (acute renal failure) and 2) CRF (chronic kidney disease).  Other factors:  CRF generally leads to anemia and small kidney size.

1)    ARF (ACUTE RENAL FAILURE)A rapid loss of renal function resulting in retention of nitrogenous (urea and creatinine) and non-nitrogenous waste products that are normally excreted by the kidney.

Ø  EPIDEMIOLOGY:  Prevalence: 5% of hospitalized patient with sepsis, shock, trauma, and surgery. 

Ø  PATHOPHYSIOLOGY:  ARF is usually categorised according to pre-renal, renal, and post-renal causes.

PRE-RENAL (from reduced renal blood supply):  Characterized by BUN/Cr ratio >20, and FENa <1% and UNa <20 (indicate intact kidneys conserving Na+ in an attempt to restore renal blood flow).  H’s --> H-hypovolemia (e.g. acute blood loss, shock, dehydration, excessive diuretics, sepsis), H-heart failure, H-HRS (hepatorenal syndrome).  Others: Use of ACE-I or NSAIDs, renal artery stenosis, atheroembolic disease, and renal vein thrombosis (can occur as a complication of the nephrotic syndrome).

§  H _______________, _______________, _______________, _______________, _______________

RENAL (damage to the kidney itself):  G-gray HAIR (I would get gray hair if I have ARF) = GHAIR --> G-gammopathy (e.g. multiple myeloma, either due to hypercalcemia or urinary cast nephropathy),  G-glomerular nephritis (e.g. from Goodpasture's syndrome, Wegener's granulomatosis or acute lupus nephritis), H-hemolysis (hemoglobin damages the tubules in disease such as SCA), H-HSP (henoch-scholein purpura and other vasculitis), A-aminoglycosides and other meds (e.g. Li+), A-autoimmune disease (e.g. SLE), A-ATN (acute tubular necrosis), I-infection (i.e. sepsis, pyelonephritis), I-intersititial nephritis (characterized by eosinophilia; SEE ALL OTHER RENAL DISEASE), R-rhabdomyolysis (caused crush injury and extensive blunt trauma, statins, stimulants and other drugs; the resultant release of myoglobin damages the kidney),

§  G ______________, ______________, ______________, ______________, _______________

§  H ______________, ______________, ______________, ______________, _______________

§  A ______________, ______________, ______________, ______________, _______________

§  I ______________, ______________, ______________, ______________, _______________

§  R ______________, ______________, ______________, ______________, _______________

POST-RENAL:  (obstructive causes in the urinary tract):  SORE (sore from urinary obstruction) --> S-stone-kidney, O-obstructive uropathy (BPH, prostate cancer, mass lesion from ovarian/colorectal cancer), R-reflux vesicoureteral, E-everything else (e.g. obstructed urinary cath, medication interfering with bladder emptying).

§  S ______________, ______________, ______________, ______________, _______________

§  O ______________, ______________, ______________, ______________, _______________

§  R ______________, ______________, ______________, ______________, _______________

§  E ______________, ______________, ______________, ______________, _______________

Ø  PRESENTATION:   Depending on the severity and duration of the renal dysfunction, this accumulation is accompanied by metabolic acidosis, and hyperkalaemia, and effects on many other organ systems. SEE PRESENTATION OF CRF. 

Ø  DIAGNOSTIC EVALUATION:  H&P.  UOP: oliguria (> 400 mL/day in adults, > 0.5 mL/kg/h in children or > 1 mL/kg/h in infants). CMP:  ↑ BUN and creatinine (necessary for diagnosis), hyperkalemia, hypercalcemia. UA and urine sediment: Check for RBCs (glomerular disease), WBCs (pyelonephritis), casts, urine eosinophilia (tubulointerstitial nephritis). Renal US:  Check for renal stone and obstruction.   Calculate FENa: FENa = (UNa/PNa)/(UCr/PCr). Kidney biopsy:  May be performed to provide a definitive diagnosis.  Consensus criteria for the diagnosis of ARF are:  

Pathologic kidney specimen showing marked pallor of the cortex, contrasting to the darker areas of surviving medullary tissue. The patient died with acute kidney injury.

Renal ultrasonograph of acute pyelonephritis with increased cortical echogenicity and blurred delineation of the upper pole.

By Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - (2015). "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics 6 (1): 2. DOI:10.3390/diagnostics6010002. ISSN 2075-4418. (CC-BY 4.0), CC BY 4.0,

Renal ultrasonograph in renal failure after surgery with increased cortical echogenicity and kidney size. Biopsy showed acute tubular necrosis.

Renal ultrasonograph in renal trauma with laceration of the lower pole and subcapsular fluid collection below the kidney.

By Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - (2015). "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics 6 (1): 2. DOI:10.3390/diagnostics6010002. ISSN 2075-4418. (CC-BY 4.0), CC BY 4.0,

Ø  TREATMENT:  Resuscitation to normotension and a normal cardiac output is key. Monitoring fluid intake and output: Insert Foley catheter to monitor UOP and relieve bladder outlet obstruction.  IVF:  First step to improve renal function in the absence of fluid overload. Central venous catheter:  Monitor fluid administration to avoid over- or under-replacement.   Electrolytes therapy:  NaHCO3 (treat metabolic acidosis), anti-hyperkalemic measures (treat hyperkalemia).  Vasopressors (norepinephrine, dobutamine):  Use if persistent hypotension in the fluid replete patient to improve cardiac output and hence renal perfusion. Swan-Ganz catheter:  May be used to measure pulmonary artery occlusion pressure to provide a guide to left atrial pressure (and thus left heart function) as a target for inotropic support.  Diuretics (e.g. furosemide):  Ameliorating fluid overload.  Specific therapy is dependent of cause of ARF:  e.g. Give corticosteroid or cyclophosphamide for some glomerulonephritis OR adjust/discontinue offending medications in tubulointerstitial nephritis.  Dialysis or hemofiltration: Indicated if therapy-resistant AEIOU --> A-acidosis, E-electrolytes disturbances (e.g. hyperK+), I-ingestion of nephrotoxic substances, O-overload (fluid), U-uremic symptoms.  Renal transplant.    

2)    CRF (CHRONIC RENAL FAILURE):  Progressive loss of renal function over a period of months or years through five stages. Each stage is a progression through a deteriorating GFR, which is usually determined indirectly by the creatinine level. 

Ø  PATHOPHYSIOLOGYEtiologies:  Diabetic nephropathy (33%), HTN (29%), and glomerulonephritis (15%) are the most common causes of CKD.   Other causes:  Vascular (e.g.  bilateral renal artery stenosis, ischemic nephropathy, HUS and vasculitis), Glomerular disease (e.g. FSGS, IgA nephritis, diabetic nephropathy and lupus nephritis), Tubulointerstitial disease (PKD, drug & toxin, and reflux nephropathy), Obstructive disease (e.g. bilateral kidney stones and diseases of the prostate).

PRESENTATION: Initially it is without specific symptoms and can only be detected as an increase in serum creatinine or protein in the urine. As the kidney function decreases, the following could be seen MOAN PHUCK → M-metabolic acidosis (due to ↓ renal H+ excretion and ↓ HCO3- synthesis), O-osteodystrophy-renal (due to ↓ vitamin D3 and renal phosphate excretion → hyperphosphatemia binds calcium → hypocalcemia → activate PTH release → tertiary hyperparathyroidism → bone resorption), A-anemia (due to ↓ EPO synthesis), N-Na+ & water retention (due to hyperreninemia), P-phosphate ↑ (due to ↓ renal excretion), P-PTH ↑, P-pyelonephritis ↑, H-HTN (due to fluid overload and production of vasoactive hormones leading to CHF, pulmonary edema), U-uremic syndrome (UREMIA → U-uremic frost, R-rales & R-rub from pericarditis, E-edema, E-energy ↓, E-encephalopathy, M-mental status changes, I-impaired immunity, A-anemia, A-asterixis, A-ascites), C-creatinine and BUN ↑, C-calciphylaxis (a syndrome of vascular calcification and skin necrosis seen almost exclusively in ESRD), C-cardiovascular disease ↑ (leading cause of death in CRF), K-K+ ↑ (due to ↓ renal K+ excretion and acidemia).

Uremic frost on the head in someone with chronic kidney disease

By Fythrion at English Wikipedia, CC BY-SA 3.0,

v  M _______________, _______________, _______________, _______________, _______________

v  O _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________

v  N _______________, _______________, _______________, _______________, _______________

v  P _______________, _______________, _______________, _______________, _______________

v  H _______________, _______________, _______________, _______________, _______________

v  U _______________, _______________, _______________, _______________, _______________

v  C _______________, _______________, _______________, _______________, _______________

v  K _______________, _______________, _______________, _______________, _______________

Ø  DIAGNOSTIC EVALUATION:  It is important to differentiate CRF from ARF because ARF can be reversible. Abdominal US:  In CRF, kidney sizes are usually smaller (< 9 cm) than normal kidneys with notable exceptions such as in diabetic nephropathy and PKD.  Serum creatinine:  Gradual rise over several months or years in CRF as opposed to a sudden increase in several days to weeks as in ARF.  All individuals with a GFR <60 mL/min/1.73 m2 for 3 months are classified as having CRF, irrespective of the presence or absence of kidney damage. The rationale this is that reduction in kidney function to this level or lower represents loss of ≥ 50% of the normal adult kidney function.  Also, all individuals with kidney damage are classified as having CRF, irrespective of the level of GFR. The rationale for including individuals with GFR ≥ 60 mL/min/1.73 m2 is that GFR may be sustained at normal or increased levels despite substantial kidney damage. STAGES:

A 12-lead ECG of a person with CKD and a severe electrolyte imbalance: hyperkalemia (7.4 mmol/l) with hypocalcemia (1.6 mmol/l). The T-waves are peaked and the QT interval is prolonged.

Chronic renal disease caused by glomerulonephritis with increased echogenicity and reduced cortical thickness. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.

By Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - (2015). "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics 6 (1): 2. DOI:10.3390/diagnostics6010002. ISSN 2075-4418. (CC-BY 4.0), CC BY 4.0,

Nephrotic syndrome. Hyperechoic kidney without demarcation of cortex and medulla

Chronic pyelonephritis with reduced kidney size and focal cortical thinning. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.

By Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - (2015). "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics 6 (1): 2. DOI:10.3390/diagnostics6010002. ISSN 2075-4418. (CC-BY 4.0), CC BY 4.0,

End-stage chronic kidney disease with increased echogenicity, homogenous architecture without visible differentiation between parenchyma and renal sinus and reduced kidney size. Measurement of kidney length on the US image is illustrated by '+' and a dashed line..

o   TREATMENT:  Goal is to slow down or halt the otherwise relentless progression of CKD to stage 5.  Anti-hyperglycemic agents:  Control of diabetes.  ACE-I or ARBs:   Control of blood pressure, and they have been found to slow the progression of CKD to stage 5.  Corticosteroid &/or cytotoxic agents:  Control glomerulonephritis.  EPO, vitamin D3, and calcium replacement:  As needed.  Phosphate binders (e.g. sevelamer): Control the serum phosphate levels.  Anti-hyperkalemic measures (e.g. loop diuretic).  Dialysis or renal transplant:  Indicated when one reaches stage 5 CKD.

·       DI (DIABETES INSIPIDUS):  Characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. 1.010-1.025 (normal specific gravity).

o   PATHOPHYSIOLOGY:  The hypothalamus regulates urine production via the synthesis of ADH or vasopressin (in the supraoptic nucleus), and it subsequent transportation in neurosecretory granules down the axon of the hypothalamic neuron to the posterior pituitary gland where it is stored for later release. ADH acts by increasing water permeability in the collecting ducts by acting on proteins called aquaporins. In addition, the hypothalamus regulates the sensation of thirst in the ventromedial nucleus by sensing increases in serum osmolarity and relaying this information to the cortex.  Forms of DI: 

1.     Central DI:   Result of damage to the hypothalamus or pituitary due to a tumor, stroke, neurosurgery or rarely hemochromatosis, sarcoidosis, histiocytosis, tuberculoma or syphilis and some genetic disorders. If the hypothalamus is damaged, the feeling of thirst may be completely absent.

2.     Nephrogenic DI:  Result of the inability of the kidney to respond normally to ADH.  Causes:  Medication (e.g. Li+ , amphotericin B, democycline), PKD, SCA, Electrolyte disturbances (e.g. hypokalaemia and hypercalcaemia), Hereditary causes (90% are due to x-linked recessive mutations of the ADH V2 receptor, and 10% mutations of the aquaporin 2 water channel; incidence:  4/million live births).

3.     Other rare form:  a) Dipsogenic DI:  Due to a defect or damage to the thirst mechanism located in the ventromedial hypothalamus. This results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output. Treatment:  Desmopressin is ineffective, and can lead to fluid overload as the thirst remains b) Gestational DI:  All pregnant women produce vasopressinase in the placenta, which breaks down ADH, this can assume extreme forms in GDI. Treatment:  Desmopressin can be use successfully.

o   PRESENTATION:  Polydipsia, polyuria and extreme thirst with a dilute urine (specific gravity <1.006). Signs of dehydration and hypernatremia (serum osmolarity > 290 mOsm/L) may also appear in some individuals.

o   DIAGNOSTIC EVALUATION:  Blood glucose levels, bicarbonate levels, and calcium:  Rule out diabetes and hypercalcemia as causes of polyuria.  Electrolytes:  detect hypernatremia as dehydration develops. UA:  Reveal dilute urine (low urine osmolality) with a low specific gravity (<1.008). Fluid deprivation test (measures changes urine output and composition when fluids are withheld):  Those with DI continue to urinate large amounts of dilute urine in spite of dehydration from not drinking fluid. While those with primary polydipsia will have less frequent urination with more concentrated urine. This distinguishes polyuria caused by DI from primary polydipsia.   Measure serum ADH.  DDAVP challenge: If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.  While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in central nervous system.  Brain MRI:  Diagnose  central DI (e.g. resulting from prolactinoma, or histiocytosis, syphilis, tuberculosis or other tumor).  Testing of other hormones of the pituitary. 

o   TREATMENT:  Central DI and gestational DI:  DDAVP (nasal spray, pill, or injection) is used effectively.  Nephrogenic DI:  HCTZ, amiloride, or indomethacin can improve NDI.   Adequate hydration is important for patients with DI, as they may become dehydrated easily.

·       SIADH (SYNDROME OF INAPPROPRIATE ADH):  Excessive release of ADH causing hyponatremia, and sometimes fluid overload.

EPIDEMIOLOGY:  Commonly found in the hospital population, especially in patients who suffered CNS injury.
PATHOPHYSIOLOGY:  Normally, a reduction in plasma osmolality is detected by hypothalamic osmoreceptors, which then switch off the release of ADH. In SIADH the release of ADH is not inhibited by a reduction in plasma osmolality. CAUSES: SIADH --> S-sarcoidosis, S-surgery, S-SCC lung cancer (as well as other small-cell malignancies of other organs), I-infection (e.g. pneumonia, lung abscess, brain abscess), A-antipsychotics, A-antidepressant, D-drugs (3 C’s --> chlorpropamide, cyclophosphamide, carbamazepine, and SSRIs, MDMA/ecstasy, oxytocin, narcotic), H-head tumor/trauma (e.g. subarachnoid hemorrhage).
Ø  S _______________, _______________, _______________, _______________, _______________

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PRESENTATION:  As the main solute of plasma is sodium, the hypoosmolar state is usually detected as a low sodium level.  Symptoms of of dilutional hyponatremia may include HA, N/V, confusion, convulsions or coma.
EVALUATION: H&P: Recent history of medication use, trauma, surgery. CBC: Rule out infection.  CMP: May reveal hyponatremia, hypokalemia, &/or hypochloremia.  Serum and urine osmolality: Diagnosis of SIADH can be made on the basis of urine osmolality >50-100 mOsm/kg with concurrent serum hyposmolarity.  Water loading test: 
TREATMENT:  Fluid restriction: If serum Na+ 120-130. Hypertonic (3%) saline IV then furosemide: If serum Na+ <120. Drugs:  Demeclocycline (ADH antagonist) and Conivaptan (antagonist of both V1A and V2 receptors).  Care must be taken when correcting hyponatremia. A rapid rise in the sodium level may cause central pontine myelinolysis (aka Schwatz-Bartter syndrome)

·       RTA (RENAL TUBULAR ACIDOSIS): A condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. Although a metabolic acidosis also occurs in those with renal insufficiency, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys.

PRESENTATION:  All forms of RTA leads to normal anion gap acidosis.  The metabolic acidosis may produce changes in pulmonary (hyperventilation, tachypnea or hyperpnea may be the only clue to acidemia), cardiovascular (tachycardia, direct impair myocardial contraction at a pH <7.2, increased risk of ventricular fibrillation), neurologic (HA, fatigue, N/V, mental confusion, stupor), and musculoskeletal (osteomalacia, rickets, osteitis fibrosa from secondary hyperparathyroidism), Genitourinary (nephrocalcinosis and urolithiasis with mainly type I distal RTA due to a high urinary pH promoting calcium phosphate precipitation. 

Significant bilateral nephrocalcinosis (calcification of the kidneys) on a frontal X-ray (radiopacities (white) in the right upper and left upper quadrant of the image), as seen in distal renal tubular acidosis.

By See below - Transferred from en.wikipedia to Commons by FastilyClone using MTC!., Public Domain,

Radiograph of a child with rickets, a complication of both distal and proximal RTA.

·       STONES (NEPRHOLITHIASIS):  Solid concretions (crystal aggregations) of dissolved minerals in urine.   M > F 4X.  Recurrence:  ~ 10%/year.

PATHOPHYSIOLOGY:  Risk factor for developing kidney stones include low fluid intake, high protein diet (protein is broken down into acids, including uric acid, which is buffed using calcium phosphate from the bones resorption, and the liberated calcium may then form insoluble crystals), hypocitruria  (citrate competes with oxalate for calcium and can thereby prevent stones), gout, or metabolic conditions (e.g. RTA) or specific enzyme deficiency (e.g. cystinuria).  Many health facilities will screen for such disorders in patients with recurrent kidney stones. Stones typically leave the body by passage in the urine. If stones grow to sufficient size before passage (> 5 mm), they can obstruct the ureter causing symptoms. 

Small crystals formed in the kidney. The most common crystals are made of calcium oxalate and they are generally 4–5 mm. Staghorn kidney stones are considerably larger. 1. Calcium and oxalate come together to make the crystal nucleus. Supersaturation promotes their combination (as does inhibition.) 2. Continued deposition at the renal papillae leads to the growth of the kidney stones. 3. Kidney stones grow and collect debris. In the case where the kidney stones block all routes to the renal papillae, this can cause severe discomfort. 4. The complete staghorn stone forms and retention occurs. Smaller solids that break off can become trapped in the urinary glands causing discomfort. 5. Displaced stones travel through the ureter. If they cannot be broken down, they must be physically removed by a surgeon.

By Darksmoke101 - Own work, CC BY-SA 3.0,

o PRESENTATION: Colicky pain: Loin to groin, often described as the "the worst pain I've ever experienced", and is due to dilation or stretching of the upper ureter and renal pelvis as well as spasm of muscle. N/V: Due to the embyrological association of the kidneys with the GI tract, which stimulates vomiting center. Hematuria: Due to damage to the lining of the urinary tract. Dysuria. Oliguria: Due obstruction of the bladder or urethra by stone, or simultaneous obstruction of both ureters by a stone.

Diagram showing the typical location of renal colic, below the rib cage to just above the pelvis

o DIAGNOSTIC EVALUATION: H&P: CVA tenderness. Murphy’s punch. UA: Microscopic study may show proteins, RBC, pus cells, bacteria, cellular casts and crystals. Urine culture: Rule out infection. CBC: Rule out leucocytosis, which suggest infection. BMP: Check renal function, hypercalcaemia. 24 hour urine: Measure daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate and phosphate. KUB: Detect the radio-opaque renal stones. IVP: A special dye is injected into the bloodstream and excreted by the kidneys. The presence of renal stone is confirmed if there is a lack of contrast filling below the stone. US: Check hydronephrosis. CT: The gold-standard diagnostic test for the immediate diagnosis of flank pain typical of a kidney stone.

Bilateral kidney stones can be seen on this KUB radiograph. There are phleboliths in the pelvis, which can be misinterpreted as bladder stones.

By Bill Rhodes from Asheville - numerous stones kub, CC BY 2.0,

Axial CT scan of abdomen without contrast, showing a 3-mm stone (marked by an arrow) in the left proximal ureter.

Renal ultrasonograph of a stone located at the pyeloureteric junction with accompanying hydronephrosis.

By Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - (2015). "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics 6 (1): 2. DOI:10.3390/diagnostics6010002. ISSN 2075-4418. (CC-BY 4.0), CC BY 4.0,

Measurement of a 5.6 mm large kidney stone in soft tissue versus skeletal CT window.

Three-dimensional reconstructed CT scan image of a ureteral stent in the left kidney (indicated by yellow arrow), with a kidney stone in the inferior renal pelvis (highest red arrow) and one in the ureter beside the stent (lower red arrow).

Radiograph showing a large staghorn calculus involving the major calyces and renal pelvis in a person with severe scoliosis.

By © Nevit Dilmen, CC BY-SA 3.0,

A color photograph of a kidney stone, 8 millimetres in length.

By Robert R. Wal -, Public Domain,

A kidney stone (yellow) composed of calcium oxalate.

Struvite crystals found on microscopic examination of the urine.

By Joel Mills - Own work, CC BY-SA 3.0,

Urine microscopy showing calcium oxalate crystals in the urine. The octahedral crystal morphology is clearly visible.

By Doruk Salancı - Own work, CC BY-SA 3.0,

Dog struvite bladder stones.

By Joel Mills - Own work, CC BY-SA 3.0,

o TREATMENT: Hydration and analgesia (e.g. NSAIDs, hydrocodone) are the initial treament. About 90% of stones ≤ 4 mm will pass spontaneously. Patients are encouraged to strain their urine so they can collect the stone and send it for chemical composition analysis to establish preventative options (used along with a 24 hour urine chemical analysis test). However the majority of stones greater than 6 mm will require some form of intervention. ESWL (Extracorporeal Shock Wave Lithotripsy): Using laser, ultrasonic or mechanical forms of energy to fragment the larger stones allowing them to pass. This method is used for stones <3 cm. Percutaneous nephrolithotomy: For large or complicated stones or stones which fail other less invasive attempts. Method to decompress the bladder: Foley catheter or suprapubic catheter. Preventive measures: Hydration (2-2.5 L of urine/day). Dietary: Decreased protein, oxalate-rich foods and maintenance of an adequate intake of dietary calcium. Medications: Thiazides (for hypercalciuria), potassium citrate or magnesium citrate (alkalinize the urine and ↑ urinary citrate level), and allopurinol (for hyperuricosuria), depending on the cause of stone formation. Calgranulin: A protein formed in the kidney and acts to inhibit crystal growth and aggregation.

A lithotriptor machine is seen in an operating room; other equipment is seen in the background, including an anesthesia machine and a mobile fluoroscopic system (or "C-arm").

By DiverDave - Own work, CC BY-SA 3.0,

A kidney stone at the tip of an ultrasonic stone disintegration apparatus.


NEPHRITIC SYNDROMES:  AKA glomerulonephritis.
Ø  PATHOPHYSIOLOGY:  The exact pathophysiology is dependent on the specific diagnosis. The common features are an inflammation of the glomeruli, leading to salt and water retention and a reduction in the kidney function. 

Ø  PRESENTATION:  PHAROH --> P-proteinuria (usually mild), H-hematuria (smoky-brown urine), A-azotemia (↑BUN), R-RBC casts, O-oliguria (<40 mL/day), H-hypertension

v  P _______________, _______________, _______________, _______________, _______________

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v  A _______________, _______________, _______________, _______________, _______________

v  R _______________, _______________, _______________, _______________, _______________

v  O _______________, _______________, _______________, _______________, _______________

v  H _______________, _______________, _______________, _______________, _______________

Ø  EVALUATION:  H&P: Recent pharyngitis, upper or lower respiratory tract symptoms (sinusitis, hemotysis).  UA: Hematuria, proteinuria.  BMP: ↑ BUN, ↑ Cr, ↓ GFR.  Complement (C3, C4): ↓ in acute cases of immune complex disease.  ANA: Rule out connective tissue disorder.  C-ANCA: Rule out WG.  Anti-GBM antibody: Rule out GP.  Kidney biopsy. 

Hematuria(one of the symptoms of Nephritic syndrome)

By Bobjgalindo - Own work, CC BY-SA 4.0,

Ø  TYPES: RAW PIG --> R-RPGN (rapidly progressive glomerular nephritis), A-alport’s syndrome, W-WG (Wegener’s granulomatosus), P-PSGN (post-streptococcal glomerular nephritis), I-IgA nephropathy, G-GP (Goodpasture’s syndrome).

v  R _______________, _______________, _______________, _______________, _______________

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Ø  RPGN (aka crescentic glomerulonephritis):   A renal syndrome, if left untreated, rapidly progresses into acute renal failure and death within months.

PATHOPHYSIOLOGY:  50% of cases are idiopathic, 50% associated with an underlying disease (e.g. GP syndrome). All types of RPGN involve severe injury to the kidney's glomeruli with >50% of the glomeruli containing characteristic crescent-shaped scars.  Severe injury and GBM rupture leads to the leakage of plasma proteins (most importantyly fibrin) through the GBM.  Epithelial cells lining the Bowman capsule and infilatrating WBCs (e.g. macrophages) respond to the leaked fibrin by proliferate. These proliferating cells surround and compress the glomerulus, forming a crescent-shaped scar that is readily visible on light microscopy of a renal biopsy.

PRESENTATION:  Severe and rapid loss of kidney function featuring P-proteinuria (can be > 3 g protein/24 h, a range associated with nephrotic syndrome), H-hematuria (smoky-brown urine), A-azotemia (↑BUN), R-RBC casts, O-oliguria (<40 mL/day, indicate a poor prognosis), H-hypertension.  Hemoptysis, sinusitis, cough, epistaxis, SOB:  When the cause of RPGN is GP syndrome or WG.

DIAGNOSTIC EVALUATION:  Serum analysis:  Anti-GBM antibodies (type I RPGN); ANA (e.g. lupus nephritis type II RPGN); ANCA (associated with type III and idiopathic RPGN).

Histopathological image of crescentic glomerulonephritis in a patient with MPO-ANCA positive rapid progressive glomerulonephritis. Hematoxylin & eosin stain.

CC BY-SA 3.0,

Crescentic glomerulonephritis.

Immunofluorescence pattern produced by binding of serum from a patient with microscopic polyangiitis to ethanol-fixed neutrophils

By Malittle at English Wikipedia - Transferred from en.wikipedia to Commons., Public Domain,

CLASSIFICATION:  3 types:  PIG --> P-pauci-immune RPGN (Type III):  Accounts for 55% of RPGN and features features antibodies directed against ANCA (no immune complex deposition or anti-GBM antibodies). It may be idiopathic (e.g. isolated to the glomerulus) or secondary to a systemic disease (e.g. the ANCA-associated vasculitis such as WG, MPA, or Churg-Strauss syndrome).  I-immune complex RPGN (Type II):  Accounts for 25% of RPGN.  Any immune complex disease that involves the glomerulus (e.g. SHIP --> SLE, HSP, IgA nephropathy, PSGN) may progress to RPGN if severe enough. GBM disease (type I):  Account for 20% of RPGN.  It is characterized by the presence of autoantibodies directed against GBM-type IV collagen (e.g. Goodpasture syndrome).

§  P _______________, _______________, _______________, _______________, _______________

§  I _______________, _______________, _______________, _______________, _______________

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v  TREATMENT:  Depends on the underlying disease.  For example:  Plasmapheresis, corticosteroids, and cytotoxic drugs may promote recovery in Goodpasture syndrome.  Despite even early treatment, however, many patients with RPGN may ultimately require dialysis and possibly renal transplant.  SEE SPECIFIC DISEASE SECTION. 

Ø  ALPORT SYNDROME:  A genetic disorder characterized by glomerulonephritis, ESRD (endstage kidney disease), and hearing loss. Alport syndrome can also affect the eyes.

EPIDEMIOLOGY:  Usually present in boys 5-20 y/o.

PATHOPHYSIOLOGY:  Caused by an autosomal dominant mutation in the COL4A3 and COL4A4, or an X-linked mutations in COL4A5 genes (more common).  This prevents the proper production or assembly of the type IV collagen network, which is an important structural component of basement membranes in the kidney, inner ear, and eye. In Alport’s syndrome, the improperly formed basement membrane allows blood and protein into the urine, and causes gradual scarring of the kidneys, eventually leading to kidney failure.    

PRESENTATION:  Patient usually have a family history of unexplained haematuria and a self-history of  persistent hematuria without evidence of another possibly inherited nephropathy (e.g. thin GBM disease, PKD or IgA nephropathy) and COLLAGEN --> C-collagen IV mutation, O-ocular lesion (e.g. anterior lenticonus, posterior subcapsular cataract, posterior polymorphous dystrophy, retinal flecks), L-lamina densa splitting in the basement membrane, L-leiomyomatosis of esophagus or female genitalia, A-alpha 5 gene mutation is most common, G-GBM ultrastructural abnormalities (e.g. thickening, thinning, splitting), E-ESRD by 30’s in the index case of at least two family members, N-neurosensory deafness (develops gradually before the age of 30). 

§  C _______________, _______________, _______________, _______________, _______________

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TREATMENT:   No cure.  Tend to recur after transplant.


Ø  PSGN (post-streptococcal glomerulonephritis):  A glomerulonephritis following an streptococci infection. This condition is essentially defined as an inflammation of the kidneys. 

PATHOPHYSIOLOGY:  A Type III hypersensitivity reaction that usually follows a strep throat infection.  Immune complexes (antigen-antibody) formed during an infection become lodged in the GBM. Complement activation leads to destruction of the basement membrane. 

PRESENTATION:  Acute nephritic syndrome with PHAROH.

DIAGNOSTIC EVALUATION:  H&P.  ASOT Ab ↑.  Complement levels ↓. Renal biopsy:  Rarely required since there is usually a classical clinical presentation.  IF: Lumpy-bumpy pattern.

TREATMENT:  Suportive.  Almost all children and most adults have complete recovery


By James Heilman, MD - Own work, CC BY-SA 3.0,

Micrograph of a post-infectious glomerulonephritis. Kidney biopsy. PAS stain.

Ø  IgA NEPHROPATHY (aka Berger's disease or synpharyngitic glomerulonephritis):  Characterized by deposition of the IgA antibody in the glomerulus. There are other diseases associated with glomerular IgA deposits, the most common being Henoch-Schönlein purpura, which is considered by many to be a systemic form of IgA nephropathy. HSP presents more commonly in young adults (16-35 yrs old) and is associated with a more benign prognosis.

EPIDEMIOLOGY:  IgA nephropathy is the most common glomerulonephritis in the world. Usually occur in young men.  M > F 3X. 

PATHOPHYSIOLOGY:  Diffuse deposit of IgA in a blotchy pattern in the mesangium (on immunofluorescence), the heart of the renal glomerulus. The tissue changes gradually from being hypercellular to depositing extracellular matrix proteins, and finally fibrosis.  There is no clear known explanation for the accumulation of the IgA.  One possible explaination is that abnormalities of the IgA1 molecule (deficiency of O-glycosylation) lead to their polymerisation in tissues, especially the glomerular mesangium.

PRESENTATION:  Commonly asymptomatic and detected through abnormal findings on UA.  The classic presentation (in 40-50% cases):  Episodic gross hematuria, which usually starts within a day of an upper respiratory tract infection.  Flank pain can also occur.  The frank hematuria resolves after a few days, though the microscopic hematuria persists.  In most patients (especially younger adults), this episodic hematuria eventually stops and renal function remains normal; however, rarely, acute renal failure may occur.  In 20%, usually the older population, there is persistent microscopic hematuria and proteinuria (<2 grams/24 hours), and gradual progression (over 20-30 yrs) to ESRD.

DIAGNOSTIC EVALUATION:  H&P:  Recent h/o an URT infection.  CBC.  BT/PT/PTT:  Rule out hemorrhagic disorder. Electrolytes, creatinine, urea, total protein and serum albumin:  Check renal function.  Other blood tests:  CRP/ESR, complement levels, ANA, ANCA, LDH. Protein electrophoresis and immunoglobulin levels:  ↑ IgA1 in 30% to 50%. Tests such as electrolytes, help in establishing the prognosis.  UA:  Show RBCs, RBC casts,  proteinuria (usually < 2 gr/day).  Renal US:  Look for stones.  Cystoscopy:  Look for bladder cancer.  Kidney biopsy (necessary to confirm diagnosis):  Shows proliferation of the mesangium.  IF/EM: IgA deposits.   

mmunostaining showing IgA in the glomerulus of a patient with Henoch-Schönlein nephritis.

By Lazarus Karamadoukis, Linmarie Ludeman and Anthony J Williams - Henoch-Schönlein purpura with intracerebral haemorrhage in an adult patient: a case report, Journal of Medical Case Reports. doi:10.1186/1752-1947-2-200, CC BY 2.0,

TREATMENT:  Benign course (isolated hematuria, proteinuria < 1 g/day and normal renal function):  Generally just followed up annually.  Moderate risk (preserved renal function and proteinuria 1-3.5 g/day):  6 months regimen of steroids may lessen proteinuria, preserve renal function and ↓ progression to ESRD.  High risk (patients with declining GFR):  A combination of steroids and cyclophosphamide for the initial 3 months followed by azathioprine for a minimum of 2 years has been shown to significantly preserve of renal function.  Other measures:  Low-protein diet and optimal control of blood pressure (ACE-Is or ARBs are favoured due to their anti-proteinuric effect).

PROGNOSIS:  IgA nephropathy has a very variable course, ranging from a benign recurrent hematuria up to a rapid progression to chronic renal failure. Male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidemia, older age, familial disease and elevated creatinine are markers of a poor outcome. IgA nephropathy may recurs in transplants despite the use of ciclosporin, azathioprine or mycophenolate mofetil and steroids in these patients.

Ø  GOODPASTURE’S SYNDROME (aka anti-GBM disease):   Characterised by rapid destruction of the kidneys and hemorrhaging of the lungs.

EPIDEMIOLOGY:  Incidence:  ~1/1,000,000 per year.  Most common between ages 18-30 and again between 50-65. M > F 6X. 

PATHOPHYSIOLOGY:  A type II hypersensitivity reaction to Goodpasture’s antigens (specifically the basement membrane's including a-3 chain of type IV collagen-COL4A3) on the cells of the renal glomeruli and the pulmonary alveoli.

PRESENTATION:  There is an increased incidence of syndactly.  Most patients present with both lung and kidney disease.  Hence T-two G-good P-pastures = 2 GP --> T-type T-two hypersensitivity reaction, G-glomerular disease (presents as nephritic syndrome with hematuria, ↓ GFR, HTN, or as Type RPGN), P-pulmonary disease (progressing dry cough and minor breathlessness to severe impairment of oxygenation and hemoptysis).  Deterioration of pulmonary and glomerular disease often occurs simultaneously. 

§  T _______________, _______________, _______________, _______________, _______________

§  G _______________, _______________, _______________, _______________, _______________

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DIAGNOSTIC EVALUATION:  H&P.  Serology:  anti-GBM antibodies, ANCA.  Kidney biopsy:  often the fastest way to secure the diagnosis and gain information about the extent of the disease and likely effect of treatment. IF: Linear anti-GBM deposit.   

High magnification micrograph showing a crescentic glomerulonephritis, also known as a rapidly progressive glomerulonephritis. PAS stain. Kidney biopsy. Immunofluorescence demonstrated linear staining with IgG, characteristic of anti-glomerular basement membrane disease, also known as Goodpasture syndrome.

By Nephron - Own work, CC BY-SA 3.0,

TREATMENT:  Plasmapheresis (remove blood plasma and its replacement with an isotonic salt and protein solution):  To ↓ anti-GBM antibodies in the blood.   Corticosteroids and immunosuppressant:   Goodpasture’s syndrome responds well to these. This course of treatment usually lasts between three and six months.  Antibiotic:  Treatment of lung infection and stopping smoking may reduce hemorrhage.  Renal transplant.

PROGNOSIS:  With treatment, the patient can usually recover completely from lung damage. Kidneys, on the other hand, are less able to repair themselves and patients with kidney damage must often resort of a life on dialysis or kidney transplantation.

NEPHROTIC SYNDROME:  Damaged kidneys leaking ≥ 3 grams/day of protein from the blood into the urine.
Ø  PATHOPHYSIOLOGY:  The renal glomeruli consist of fenestrated capillaries, which normally allow fluid, salts, and other small solutes to flow through, but not proteins.  In nephrotic syndrome, the glomeruli become damaged so that small proteins (e.g. albumins, immunoglobulins, and anti-thrombin) can pass through the kidneys into urine.  The edema formation in nephrotic syndrome is due to the loss of albumin (due to loss of colloid osmotic pressure), microvascular damage, and intense salt and water retention by the damaged kidneys (due to increased angiotensin secretion).  The hyperlipidemia and hyperlipiduria is due increased hepatic protein synthesis (including a2-macroglobulin and lipoproteins) as a response to leakage of albumin.  The excess lipoproteins end up in the urine filtrate and are rebsorbed by the tubular cells, which end up shedding and forming oval fat bodies or fatty casts.

Ø  PRESENTATON:  HEAP (think of the loss of a heap of protein) --> H-hypoalbuminemia, H-hyperlipidemia, E-edema in dependent area (puffiness around the eyes characteristically in the morning, pitting edema over the legs, pleural effusion, ascites), E-encapsulated bacterial infection (due to loss of immunoglobulins and complements), A-AT-III (anti-thrombin III) loss causing thrombus formation, P-proteinuria.

v  H _______________, _______________, _______________, _______________, _______________

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Nephrotic syndrome is usually accompanied by retention of water and sodium. The degree to which this occurs can vary between slight edema in the eyelids that decreases during the day, to affecting the lower limbs, to generalized swelling, to full blown anasarca.

By CharlesPicavet - Own work, Public Domain,

Ø  DIAGNOSTIC EVALUATION:  UA: Proteinuria, Urinary cast, Maltese cross (evident in fatty casts with polarized microscopy due to cholesterol.  BMP:  Evaluate renal function.  Albumin: ↓ < 3g/dL.  FLP:  Hypercholesterolemia (↑ LDL). LFT: Rule out hepatic causes of hypoalbuminemia.  Autoimmune markers:  ANA, ASO, C3/C4, Cryoglobulins, SPEP.  CXR & Echocardiography: Rule out cardiac causes of edema.  Renal biopsy.

Microscopic image of diabetic glomerulosclerosis, the main cause of nephrotic syndrome in adults.

Diabetic glomerulonephritis in a patient with nephrotic syndrome.

By No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims)., CC BY-SA 3.0,

Ø  TREATMENT:  General measures (supportive):  Dietary (limit protein, fats, K+, Na+ intake), Monitoring and maintaining euvolemia (monitor UOP, BP, and fluid restrict to 1L), Monitoring kidney function (daily BMP, calculating GFR).  Specific treatment of underlying cause:  Glomerular nephritis (prednisolone 60mg/day or cyclophosphamide cyclosporin in refractory cases), DM (tight blood suger control), HTN (ACE-Is or ARBs are the drug of choice shown to decrease protein loss), Hyperlipiduria (antihyperlipidemics), Venous thrombosis (treat with oral anticoagulants and not heparin as heparin acts via AT-III which is lost in the proteinuria), Infection with encapsulated bacteria such as Haemophilus influenzae and Streptococcus pneumonia (antibiotics).

Ø  TYPES OF NEPHROTIC SYNDROME:  Nephrotic syndrome may either be the result of a disease limited to the kidney (primary), or a condition that affects the kidney and other parts of the body (secondary). A-all MD’s S-skip F-foreplay = AMDSFP --> A-amylodosis, M-MCD (minimal change disease), M-membranous nephropathy, M-membranoproliferative glomerulonephritis, D-diabetic nephropathy, S-SLE-induced, S-sarcoidosis, F-FSGS (focal segmental glomerulosclerosis). 

v  A _______________, _______________, _______________, _______________, _______________

v  M _______________, _______________, _______________, _______________, _______________

v  D _______________, _______________, _______________, _______________, _______________

v  S _______________, _______________, _______________, _______________, _______________

v  F _______________, _______________, _______________, _______________, _______________


Ø  MCD (aka lipoid nephrosis):   

v EPIDEMIOLOGY:  The most common nephrotic syndrome in children (peak incidence at 2-3 y/o).

PATHOPHYSIOLOGY:  Most are idiopathic but can be associated with food allergies, medications, or hematologic malignancies. The pathology involved an abnormal secretion of lymphokines by T cells.  This reduces the production of anions in the GBM, thereby increasing the glomerular permeability to serum albumin through a reduction of electrostatic repulsion. The loss of anionic charges is also thought to favor foot process fusion.  It does not appear to involve complement, immunoglobulins, or immune complex deposition. Conditions associated with T-cell abnormalities (Hodgkin's disease and T-cell lymphoma) are sometimes associated with MCD.

PRESENTATION:  HEAP --> H-hypoalbuminemia, H-hyperlipidemia, E-edema in dependent area, P-proteinuria.   

DIAGNOSTIC EVALUATION:  Renal biopsy.  LM:  Normal.  EM:  Podocyte foot process effacement.

TREATMENT:  Prednisone and ACE-I.   Anti-hyperlipidemic (e.g. statin):  Often prescribed for the duration of the treatment. 50% of patients will relapse and need further treatment.  Recurrence rate: 80%.

The three hallmarks of minimal change disease: diffuse loss of podocyte foot processes, vacuolation, and the appearance of microvilli.

By Renal_corpuscle.svg: M•Komorniczak -talk- (polish Wikipedist)derivative work: Huckfinne (talk) - Renal_corpuscle.svg, CC BY-SA 3.0,

Ø  MEMBRANOUS NEPHROPATHY:  An immunologic renal disorder characterized by subepithelial immune deposits (antigen-antibody complexes) in the glomerular capillary wall.

EPIDEMIOLOGY:  The #3 cause of nephrotic syndrome in adults.

PATHOPHYSIOLOGY:  The antigen-antibody complexes are formed by antibodies against cationic antigens crossing the anionic glomerular barrier.  Although primary (idiopathic) membranous predominantly has mainly subepithelial deposits, secondary membranous may be characterized by subendothelial deposits and mesangial deposits. Secondary causes include:  SHAM --> S-sarcoidosis, H-hepatitis B & C, A-autoimmune disease (e.g. RA, SLE, Sjögren's syndrome), M-medications (penicillamine, gold salts, Diclofenac and some other NSAIDs).  Lupus nephritis and Hep B are the only MN with a low complement level.

§  S _______________, _______________, _______________, _______________, _______________

§  H _______________, _______________, _______________, _______________, _______________

§  A _______________, _______________, _______________, _______________, _______________

§  M _______________, _______________, _______________, _______________, _______________

PRESENTATIONHEAP --> H-hypoalbuminemia, H-hyperlipidemia, E-edema in dependent area, P-proteinuria.  

DIAGNOSTIC EVALUATION:  LM:  Thickened capillary walls.  IF:  IgG and C3 deposits in a granular pattern along the capillary wall.  Silver stain:   Spikes and domes corresponding to the immune deposits. EM:  Subepithelial electron dense deposits.

TREATMENT:  The prognosis is variable. In many cases, there is spontaneous remission. Mild disease:  No treatment required.  Severe disease (decreasing renal function and a high level of proteinuria):  Therapy with steroids and cytotoxics (cyclophosphamide, mycophenolate mofetil).   In refractory cases, ciclosporin may also be useful.

Very high magnification micrograph of membranous nephropathy, abbreviated MN. MN may also be referred to as membranous glomerulonephritis, abbreviated MGN. Kidney biopsy. Jones stain. The characteristic feature on light microscopy is basement membrane thickening/spike formation, which is best seen with silver stains. On electron microscopy, subepithelial deposits are seen.

By Nephron - Own work, CC BY-SA 3.0,

Ø  MPGN (Membranoproliferative glomerulonephritis):  Can also be a nephritic syndrome. 

PATHOPHYSIOLOGY:  Immune complexes depositing in the kidney mesangium and GBM, activating complement and damaging the glomeruli. The GBM is rebuilt ontop of the deposits, causing a "tram-tracking" appearance under the microscope.   The most common cause of MPGN is hepatitis C. 

PRESENTATION:  HEAP --> H-hypoalbuminemia, H-hyperlipidemia, E-edema in dependent area, P-proteinuria.  

DIAGNOSTIC EVALUATION:  IF: Tram-track (double-layered GBM).  TYPES OF MPGN:

1.     Type I:  The most common.  It is described above.

2.     Type II (dense deposit disease):  The material deposited is not immune complexes.  It involves a C3 nephritic factor and ↓ C3.

3.     Type III:  Very rare, it is characterized by a mixture of subepithelial deposits and the typical pathological findings of Type I disease.

TREATMENT: Corticosteroids and cytotoxic agents may help.

Micrograph of glomerulus in membranoproliferative glomerulonephritis with increased mesangial matrix and increased mesangial cellularity. Kidney biopsy. PAS stain.

Ø  DIABETIC NEPHROPATHY (aka Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis):  A progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli.

EPIDEMIOLOGY:  Seen in chronic diabetes (≥ 15 years after onset), so patients are usually of older (50-70 y/o). It is the most common cause of chronic kidney failure, ESRD, and dialysis in the US. The risk is higher if blood-glucose, hypertension and hyperlipidemia are poorly controlled.

PATHOPHYSIOLOGY:  The earliest detectable change is a thickening in the glomerulus. At this stage, the kidney microalbuminuria develops.  This can appear 5 to 10 years before other symptoms. As diabetic nephropathy progresses, increasing numbers of glomeruli are destroyed by nodular glomerulosclerosis or diffuse hyalinization. 

Diagram showing the basic outline of nephron structure and function: diabetic nephropathy is associated with changes in the afferent and efferent arterioles, causing capillary hypertension; and damage to the glomerular capillaries of multiple causes, including mesangial matrix deposition

By Madhero88 - Own workReferenceshere, CC BY 3.0,

PRESENTATION:  Asymptomatic in its early course.  In latter stages, symptoms arise from loss of protein or renal failure and include:  Anorexia, N/V, malaise, fatigue, HA, and HEAP --> H-hypoalbuminemia, H-hyperlipidemia, E-edema in dependent area (and weight gain from fluid accumulation), P-proteinuria.   Other possible symptoms/signs:  HTN (from fluid retention) and arteriosclerosis of the renal artery.

DIAGNOSTIC EVALUATION: UA: Microalbuminuria-proteinuria, glycosuria. BMP: BUN & creatinine ↑. Renal biopsy (confirms the diagnosis): ↑ mesangial deposit of PAS-positive material of two patterns 1) diffuse hyalinization or 2) nodular glomeurlosclerosis (aka Kimmel Stiel-Wilson). Opthalmic exam: Look for concurrent diabetic retinopathy.

Two glomeruli in diabetic nephropathy: the acellular light purple areas within the capillary tufts are the destructive mesangial matrix deposits.

TREATMENT:  Lifestyle:  Monitor calorie consumption help control blood-sugar levels and ↓ protein intake lessen renal injury. Patients with diabetic nephropathy should avoid taking the following drugs:Contrast agents containing iodine Commonly used non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, or COX-2 inhibitors like Celebrex, because they may injure the weakened kidney. Tight blood-glucose levels control:  This may slow the progression of the disorder, especially in the very early ("microalbuminuria") stages.   Blood pressure control:  ↓ the risks of kidney, eye, and blood vessel damage in the body. The choice is an ACE-I or ARB, which ↓ proteinuria and slows the progression of diabetic nephropathy. Hyperlipidemia control:  Maintain a healthy weight, engage in regular physical activity, and use of statins.  Dialysis and renal transplant:  Considered once ESRD develops.

Ø  SLE (lupus nephritis):  Inflammation of the kidney caused by systemic lupus erythematosus (SLE).

PRESENTATION:  Renal disease can manifest as HEAP --> H-hypoalbuminemia, H-hyperlipidemia, H-hyperlipiduria (darker foamy urine), H-HTN, E-edema in dependent area (swelling around the eyes, legs, ankles or fingers, and weight gain), P-proteinuria.   Furthermore, patients may suffer from other symptoms of lupus unrelated to kidney function (e.g. arthritis, fevers, gastro-intenstinal disturbances, headaches, fatigue, and synovitis).

DIAGNOSTIC EVALUATION:  BMP: Blood sugar, electrolytes.  UA: Microalbuminuria, proteinuria.  Renal US. Renal biopsy. IF: Mesangial proliferation and subendothelial immune complex deposits (wire loop).  The WHO has divided lupus nephritis into five classes based on the biopsy:

Diffuse proliferative lupus nephritis as seen in a pathology specimen

By, Public Domain,

Micrograph of diffuse proliferative lupus nephritis showing increased mesangial matrix and mesangial hypercellularity. Kidney biopsy. PAS stain.

Membranous nephropathy.

TREATMENTLifestyle:  Monitor intake of protein, sodium (<2g/day), and potassium. Medicines:  Lasix (↓ swelling).  Anti-hypertensive (ACE-I):  Control blood pressure.  Anti-rheumatic drugs:  Depending on the histology, renal function and degree of proteinuria, patients may require steroid therapy or chemotherapy (e.g. cyclophosphamide, azathioprine, mycophenolate mofetil, or cyclosporine). Mild disease:  Corticosteroids.  More severe disease:  Immunosuppressant agents with the 2 most commonly-used agents are mycophenolate mofetil (first-line) and IV cyclophosphamide.

Ø  FSGS (Focal Segmental GlomeruloSclerosis):   

EPIDEMIOLOGY:  #1 cause of nephrotic syndrome in young black male.  #2 nephrotic syndrome overall.

v  PATHOPHYSIOLOGY:  Primary FSCS (usually present with nephrotic syndrome):  Idiopathic or hereditary etiologies.  Known genetic causes of the hereditary FSGS:  ACTN4 gene (alpha-actinin 4),TRPC6 gene, p130(Cas) ligand gene, NPHS2 gene (the protein product of these genes are expressed in podocytes and their mutation alters podocyte cytoskeletal architecture).  All are autosomal dominant inherited except for NPHS2 gene, which is autosomal recessive and is resistant to treatment with steroids.   Secondary (usually present with renal failure and proteinuria):  This form is associated with HIV --> H-HIV associated nephropathy, I-infection (chronic pyelonephritis), IVDU (heroin), V-vesicoureteral reflux, pamidronate use, morbid obesity, and diabetes mellitus

§  H _______________, _______________, _______________, _______________, _______________

§  I _______________, _______________, _______________, _______________, _______________

§  V _______________, _______________, _______________, _______________, _______________

PRESENTATIONHEAP --> H-hypoalbuminemia, H-hyperlipidemia, H-hyperlipiduria (darker foamy urine), H-HTN, E-edema in dependent area (swelling around the eyes, legs, ankles or fingers, and weight gain), P-proteinuria.  

DIAGNOSTIC EVALUATION:  UA.  FLP.  Renal biopsy:  The name refer to the appearance of the kidney tissue on biopsy --> Focal - only some of the glomeruli are involved (as opposed to diffuse), Segmental - only part of an entire glomerulus is involved (as opposed to global), glomerulosclerosis - refers to scarring of the glomerulus.  Five mutually exclusive variants of FSGS:  Distinguished by histology, and each has prognostic significant:  1) Collapsing variant (associated with higher rate of progression to ESRD) 2) Glomerular tip lesion variant (low rate of progression to ESRD) 3) Cellular variant (similar clinical presentation to collapsing and glomerular tip variant but has intermediate outcomes between these two variants) 4) Perihilar variant  5) Not otherwise specified variant (most common type.  The prognostic significance of perihilar and NOS variants has not yet been determined.

Micrograph of the collapsing variant of FSGS (collapsing glomerulopathy). A collapsed glomerulus is seen at the top, right-of-centre. PAS stain. Kidney biopsy.

By Nephron - Own work, CC BY-SA 3.0,

High magnification micrograph of focal segmental glomerulosclerosis, hilar variant. Focal segmental glomerulosclerosis is commonly abbreviated FSGS. PAS stain. Kidney biopsy. It presents as a nephrotic syndrome.

TREATMENT:  Lifestyle:  Monitor intake of protein, sodium (<2g/day), and potassium. Medicines:  Lasix (↓ swelling).  Anti-hypertensive (ACE-I):  Control blood pressure.  Anti-hyperlipidemics:  Statins, fibrates.  Anti-rheumatic drugs:  Depending on the histology, renal function and degree of proteinuria, patients may require steroid therapy or chemotherapy (e.g. cyclophosphamide, azathioprine, mycophenolate mofetil, or cyclosporine). Mild disease:  Corticosteroids.  More severe/refractory disease:  Immunosuppressant such as IV cyclophosphamide.  Plasmapheresis.  Dialysis and renal transplant.    

·       URETERAL REFLUX (aka vesicoureteral reflux):  Retrograde movement of urine from the bladder into ureters or kidneys.

EPIDEMIOLOGY:  Prevalence: 10% of the population.  F > M (85% of VUR occur in female).  Younger children are more prone because of the relative shortness of the ureters. This susceptibility decreases with age.   
PATHOPHYSIOLOGY:  Normally, the ureters enter the urinary bladder obliquely and run submucosally for some distance. This in addition to the ureter's muscular attachments produce a valve like effect that occludes the ureteric opening during storage and voiding of urine. In people with VUR failure of this mechanism occurs with resultant retrograde flow of urine.  Primary VUR: Insufficient submucosal length of the ureter relative to its diameter causes inadequacy of the valvular mechanism. Secondary VUR:  Valvular mechanism is overwhelmed by raised vesicular pressures (e.g. obstructive causes like posterior urethral valves, urethral or meatal stenosis or functional causes like neurogenic bladder UTI). 
PRESENTATION:  Recurrent UTI (fever, abdominal pain, dysuria, frequency, malodorous urine). 
DIAGNOSTIC EVALUATION:  Abdominal US and VCUG (voiding cystourethrogram):  Method of choice for detecting anatomic abnormalities and grading of VUR.  

Medical ultrasound image showing abnormal vesicoureteral junction and dilated distal ureter resulting in primary vesicoureteral reflux (VUR). Insufficient submucosal length of the ureter relative to its diameter causes inadequacy of the valvular mechanism which prevents reflux. In healthy individuals the ureters enter the urinary bladder obliquely and run submucosally for some distance.

By © Nevit Dilmen, CC BY-SA 3.0,

VCUG demonstrating bilateral Grade II (non-dilating) vesicoureteral reflux.

o   TREATMENT:  Lifestype:  Good perineal hygiene, timed and double voiding. Medical therapy (recommended in children with Grade I-III VUR as 85% will resolve spontaneously):   Low-dose antibiotic prophylaxis until resolution of VUR (ceplatosportin, amoxicillin-especially for children, nitrofurantoin, or bactrim, is give nightly at half the normal therapeutic dose).  Urine cultures: Performed q3 months to exclude breakthrough infection. Annual radiological investigations. Bladder dysfunction is treated with the administration of anticholinergics. Surgical Management:  Ureteral reimplantation is indicated for Grade IV & V and those failed medical therapy.


EPIDEMIOLOGY:  The most common life-threatening genetic disease worldwide. Prevalence:  1/1000 people for the autosomal dominant type; 1/20,000 people for the autosomal recessive type.
PATHOPHYSIOLOGY:  Autosomal dominant form (ADPKD):  85% caused by mutations in the gene PKD1 (polycystin-1); 15% by mutations in PKD2 (polycystin-2).  Autosomal recessive (ARPKD): Due to mutations in the PKHD1 gene (chromosome 6).  Environmental sensing initiated from proteins inserted into ciliary/flagellar membranes is thought to be critical for normal renal cell development and functioning.  Mutation of PKD1 and PKD2, which encode membrane proteins, lead to defects in the assembly of the cilium on the renal tube cell.  Failure in flow-sensing signaling results in programmed cell death or apoptosis of these renal epithelial cells producing the characteristic multiple cysts of PKD.   Knudson hypothesis 2-hit hypothesis can be used to explain ADPKD.

PKD1 and PKD2

By Kuebi = Armin Kübelbeck - Own work, CC BY-SA 3.0,

Cartoon of autosomal dominant polycystic kidney disease with normal kidney inset to right of diagram

o PRESENTATION: ADPKD: Usually > 30 y/o with progressive multicystic development and bilaterally renal enlargement, renal pain, and renal insufficiency. 50% of ADPKD have ESRD by the age of 60. Other site of cyst formation: Liver (lead to cirrhosis), seminal vesicles, pancreas, and arachnoid mater. Other common complaints: Cerebral berry aneurysms, dolichoectasias, dilatation of the aortic root and dissection of the thoracic aorta, mitral valve prolapse, and abdominal wall hernias. ARPKD: Usually apparent at birth or in early infancy with renal failure, liver fibrosis, portal HTN follwing by death within the first few years.

o DIAGNOSTIC EVALUATION: US or CT scan: Multiple bilateral renal cysts, renal enlargement, and cysts in aother organs.

Severely affected polycystic kidneys removed at time of transplantation

By, Public Domain,

CT scan showing autosomal dominant polycystic kidney disease

o TREATMENT: Preven complications and progression to ESRD. Pain control: Meds (e.g. Tylenol), surgery (shrink cysts can relieve back pain). UTIs: Early treatment is critical to prevent spread to the renal cysts. Cyst infections are difficult to treat because many antibiotics do not penetrate into the cysts. HTN: Blood pressure control can slow the effects of PKD. Dialysis or transplantation: For ESRD.

·       TUBULAR AND INTERSTITIAL DISEASERAT --> R-renal papillary necrosis, A-ATN (acute tubular necrosis), T-tubulointerstitial nephritis.

o   R _______________, _______________, _______________, _______________, _______________

o   A _______________, _______________, _______________, _______________, _______________

o   T _______________, _______________, _______________, _______________, _______________

o   RENAL PAPILLARY NECROSIS:  Pathophysiology:  Ischemic necrosis of the renal papilla, which is supplied by the vasa recta.  Etiology:  Primarily associated with diabetes mellitus, but can be caused by the 2P’s  (as in P-papillary) --> P-pyelonephritis, P-phenacetin use (from chronic analgesic nephritis).

Ø  P _______________, _______________, _______________, _______________, _______________

Frontal section through the kidney

Public Domain,


Ø  PATHOPHYSIOLOGY: Death of cells that form the renal tubule.  Necrotic cells fall into the tubule lumen, obliterating it, and causing acute renal failure. ATN is classified as either toxic or ischemic (more common). Toxic ATN (damage usually limited to the PCT): Caused by free hemoglobin or myoglobin (from crush injury) or nephrotoxin (GEM --> G-gentamincin, E-ethylene glycol, M-mercuric chloride).  Ischemic ATN (causes skip lesions through-out the tubules):  Caused by renal ischemia occurs during shock/sepsis or renal artery stenosis. 

Ø  PRESENTATION:  Usually present as ARF (acute renal failure). 

Ø  DIAGNOSTIC EVALUATION:  UA:  Muddy brown casts of epithelial cells is pathognomonic for ATN.  Renal biopsy: Tubular epithelium necrosis (no nuclei, intense eosinophilic homogeneous cytoplasm, but preserved shape), while the basement membrane is intact, so the tubular epithelium regeneration is possible. Glomeruli are not affected. 

Ø  TREATMENT: Remove inciting factor and promt dialysis as most death occurs during the intitial oliguric phase from hyperkalemic-induced arrythmia.  Necrotic tubular cells will be replaced in ~ 2 weeks with return of renal function.

Ø  SUMMARY OF ATNATN --> usually present as A-ARF, T-two T-types T-toxic (due to myoglobinuria and nephrotoxins) and N-non-toxic/ischemic (due to renal hypoperfusion).

v  A _______________, _______________, _______________, _______________, _______________

v  T _______________, _______________, _______________, _______________, _______________

v  N _______________, _______________, _______________, _______________, _______________


o   TIN (TUBULOINTERSTITIAL NEPHRITIS aka interstitial nephritis):   Can be acute or chronic.

Ø  PATHOPHYSIOLOGY:  Etiolologies:  Allergic reaction to a drug:  The most common cause (71-92%) of interstitial nephritis. The time between drug exposure and the development of acute tubulointerstitial nephritis can be anywhere from 5 days to 5 weeks. These drugs include S-some F-foul M-meds C-cause R-renal N-nephritis = SFDCRN --> S-sulfonamides, F-furosemide, M-methicillin, C-cephalosporins, C-cyclosporine, R-rifampin, N-NSAIDs). 

v  S _______________, _______________, _______________, _______________, _______________

v  F _______________, _______________, _______________, _______________, _______________

v  M _______________, _______________, _______________, _______________, _______________

v  C _______________, _______________, _______________, _______________, _______________

v  I _______________, _______________, _______________, _______________, _______________

v  N _______________, _______________, _______________, _______________, _______________

Other causes:  TIN --> T-transplant rejection, I-infections (pyelonephritis, HIV, CMV, histoplasmosis, toxoplasmosis, hep B), I-immunologic diseases (SLE, Goodpasture’s disease), N-neoplasia (leukemia, multiple myeloma).

v  T _______________, _______________, _______________, _______________, _______________

v  I _______________, _______________, _______________, _______________, _______________

v  N _______________, _______________, _______________, _______________, _______________

Ø  PRESENTATION:  Can be asymptomatic.  Symptoms widely varied and can include fever (27% of patients), rash (15% of patients), enlarged kidneys, N/V, fatigue, dysuria, lower back pain, weight loss, and kidney failure.

Ø  DIAGNOSTIC EVALUATION:  H&P: Recent medications, infection. CBC: Eosinophilia (23% of patient).  UA:  Eosinophiluria, Isosthenuria (urine specific gravity equals plasma’s).  Gallium scan.

Ø  TREATMENT:  Remove underlying etiology (e.g. drugs, infection). Supportive therapy: IVF.  Corticosteroids: Speed recovery in allergic reaction.  In most cases kidney function will return after when the underlying disease is cured by treatment. If not, dialysis or transplant may be needed.

·       TUMORSBenign tumor: Oncocytoma and angiomyolipoma.  Malignant tumor:  Wilm’s tumor and RCC (renal cell carcinoma).

o BENIGN RENAL TUMOR: Oncocytoma and angiomyolipoma

Ø  ANGIOMYOLIPOMA:  A benign renal lesion composed of variable amounts of fat, vascular, and smooth muscle elements. Associated condition:  Occurs in 50% tuberous sclerosis patient (often bilateral), and 40% of women with a cystic lung disease called LAM (lymphangioleiomyomatosis). Diagnostic evaluation:  CT (the fat density of the tumour on CT is pathognomonic).

Angiomyolipoma in both kidneys (arrows) in computer tomography. The tumours are hypodense (dark) due to fat content

By Hellerhoff - Own work, CC BY-SA 3.0,

Angiomyolipoma seen as a hyperechoic mass in the upper pole of an adult kidney on renal ultrasonography.

Renal ultrasonography of a person with tuberous sclerosis and multiple angiomyolipomas in the kidney: Measurement of kidney length on the US image is illustrated by ‘+’ and a dashed line.

By Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - (2015). "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics 6 (1): 2. DOI:10.3390/diagnostics6010002. ISSN 2075-4418. (CC-BY 4.0), CC BY 4.0,

Myoid cells with clear cytoplasm spinning off of large vessels in a background of mature fat, the classic microscopic features of angiomyolipoma.

Ø  ONCOCYTOMA:  An epithelial tumor composed of oncocytes thought to arise from the intercalated cells of renal collecting ducts.  Epidemiology:  Constitutes 5%-15% resected renal neoplasms. Presentation: Mostly asymptomatic and discovered incidentally on abdominal US or CT.  Posible symptoms: Hematuria, flank pain, abdominal mass.  They may be up to 12 cm in diameter. Renal biopsy:  Grossly, oncocytoma are tan or mahogany brown, well circumscribed and contain a central scar.   Histologically, there are oncocytes (large eosinophilic cells having small, round, benign-appearing nuclei with large nucleoli and numerous mitochondria).  Treatment:  Cured by nephrectomy.

Gross appearance of the cut surface of a nephrectomy specimen containing a renal oncocytoma. Note the rounded contour, the mahogany colour and the central scar.

By Emmanuelm at English Wikipedia, CC BY 3.0,

Micrograph of a renal oncocytoma. H&E stain.

Micrograph of a renal oncocytoma. H&E stain.

By Nephron - Own work, CC BY-SA 3.0,


Ø  WILM’S TUMOR (aka nephroblastoma):   Embryonal renal tumor.

EPIDEMIOLOGY: US incidence:  500 cases/year.  Most occur in children 2-4 y/o, with 75% occur in otherwise normal children and 25% associated with other developmental abnormalities. 

PATHOPHYSIOLOGY:  Mutations of the WT1 gene (chromosome 11) are observed in 20% of Wilms' tumors.   Also, the WTX gene (X chromosome) is inactivated in 30%. 

PRESENTATION:  Painless abdominal/flank mass that does not cross the midline, frequency, dysuria, hematuria, HTN (due to renin release or compression of renal vasculature), bone pain (from metastasis), and constitutional symptoms (fever, N/V).  Wilm’s tumor may occur in the setting of Beckwith-Wiedemann syndrome, WAGR syndrome and Denys-Drash syndrome.

DIAGNOSTIC EVALUATION:  H&P.  BMP: Assess renal function.  Abdominal CT/US: Assess the primary tumor.  CXR, CBC, LFT: Assess metastasis.  Renal biopsy:  Triphasic nephroblastoma comprises three elements metanephric blastema (with glomerular differentiation),  mesenchyme (stroma may include striated muscle- rhabdomyoid component may show features of malignancy hence rhabdomyosarcomatous Wilms, cartilage, bone, fat, and fibrous tissue), and epithelium.   Also characteristically contain abortive tubules and glomeruli surrounded by a spindled cell stroma.   

CT Scan of 11 cm Wilms' tumor of right kidney in 13-month-old.

Cut section showing two halves of a nephroblastoma specimen. Note the prominent septa subdividing the sectioned surface and the protrusion of tumor into the renal pelvis, resembling botryoid rhabdomyosarcoma.

By The Armed Forces Institute of Pathology - Image and description are from the AFIP Atlas of Tumor Pathology, according to entry #407018 in Pathology Education Instructional Resource. The Armed Forces Institute of Pathology Electronic Fascicles (CD-ROM Version of the Atlas of Tumor Pathology) contains U.S. Government work which may be used without restriction.[1], Public Domain,

Micrograph showing the characteristic triphasic pattern consisting of tubules, solid sheets of small round cells, and stroma. H&E stain.

High magnification micrograph showing the epithelial component (tubules). H&E stain.

By Nephron - Own work, CC BY-SA 3.0,

Ø  PROGNOSIS:  Highly responsive to treatment, with about 90% of patients surviving at least five years.


1.     Beckwith Wiedemann syndrome:  Prevalence: 1/15000.  Children conceived by IVF are 3-4X more likely to develop the condition.  Pathophysiology:  The BWS gene locus on chromosome 11 is adjacent to the WT1 gene implicated in Wilms' tumor.  Presentation:  MOTH --> M-macrosomia (due to hyperinsulinemia), M-macroglossia (occurs 80% of cases and often require treatment with tracheotomy), O-omphalocele, O-organomegaly (adrenocortical cytomegaly, hemihypertrophy), T-tumor (e.g. Wilm’s tumor), H-hyperinsulinemia --> H-hypoglycemia and H-hemihypertrophy.

v  M _______________, _______________, _______________, _______________, _______________

v  O _______________, _______________, _______________, _______________, _______________

v  T _______________, _______________, _______________, _______________, _______________

v  H _______________, _______________, _______________, _______________, _______________

2.     WAGR syndromePathophysiology:  Mutation on chromosome 11 including the PAX6 ocular development gene and the WT1 (Wilms' tumor gene).  Presentation:  WAGR --> W-wilms tumor, A-aniridia (absence of the iris), G-genitourinary anomalies (e.g. gonadoblastoma), R-retardation.  Diagnostic evaluation:  Chromosomal analysis is necessary for definitive diagnosis.

v  W _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________

v  G _______________, _______________, _______________, _______________, _______________

v  R _______________, _______________, _______________, _______________, _______________

3.     Denys-Drash syndrome:  Epidemiology: Very rare with only 160 reported cases worldwide since 1967. Majority of cases were males between 0-2 y/o.  Pathophysiology:  Its cause is a variation in the Wilm's tumor suppressor gene, WT1, on chromosome 11. Presentation: Gonadal dysgenesis, nephropathy (i.e. mesangial sclerosis) leading to decreased activity, low weight, loss of growth, abnormal skeletal development, abdominal pain and severe constipation.

·       RCC (renal cell carcinoma):  Adenocarcinoma arising from the renal tubule.           

o   EPIDEMIOLOGY:  #1 renal malignancy (85% of renal tumors).  US incidence: 31,000/yr. Patient usually > 55 y/o.  M > F.  Risk factors:  Smokers, von Hippel-Lindau disease, obesity, family history of kidney cancer, and kidney disorders that require dialysis.

o   PRESENTATION:  H&P: Classic triad H-hematuria, P-palpable abdominal mass, P-pain in the flank pain and P-paraneoplastic syndrome (P-PTHrP --> hypercalcemia, EPO --> P-polycythemia, P-PRL --> nipple discharge, ACTH --> hypercortisolism,  Gonadotropin --> hirsutism, Renin --> HTN), P-pathologic fractures (if metastasis to the bone), varicocele (occur in 11%, due to invasion and blockage of the renal vein, L > R because the right gonadal vein drains directly into the IVC), constipation, constitutional symptoms (weight loss, anorexia).  Majority of renal tumors are asymptomatic and detected incidentally on imaging.

Ø  H _______________, _______________, _______________, _______________, _______________

Ø  P _______________, _______________, _______________, _______________, _______________

DIAGNOSTIC EVALUATION:  H&P.  CBC:  Polycythemia.  Renal US/CT:  Characteristic appearance of a contrast enhancing solid renal lesion with an irregular or lobulated margin, which disturbs the renal contour. Renal biopsy:  Atypical polygonal tumor cells forming cords, papillae, tubules or nests. Their cytoplasm appears "clear" (due to accumulation of glycogen and lipids), the nuclei remain in the middle of the cells, and the cellular membrane is evident. The stroma is reduced, but well vascularized.   Furhman’s grading. 

Renal cell carcinoma

By User:Emmanuelm, CC BY 3.0,

Renal cell carcinoma

High magnification micrograph of a clear cell renal cell carcinoma. H&E stain. Features: Cells with clear cytoplasm, typically arranged in nests. Nuclear atypia is common. The case seen in the image has Fuhrman grade 2/4; the nuclear atypia is moderate and nucleoli could not be seen at 100 X.

By Nephron - Own work, CC BY-SA 3.0,

Micrograph of embolic material in a kidney removed because of renal cell carcinoma (cancer not shown). H&E stain.

·       ACID-BASE


Normally, human ECF (extracellular fluid) is maintained at pH 7.35-7.45. Outside of this range, proteins are denatured and digested, enzymes lose their ability to function, and the body is unable to sustain itself.

1.     Volitile acid:  H2CO3  (carbonic acid) is the sole volatile acid.  The by-product of metabolism, CO2, enters the blood and is combined with H2O to produce carbonic acid (i.e. CO2 + H2O ⇌ H2CO3).  After it is transported to the lung by RBC, the reverse reaction occurs and CO2 is expelled by the lung.  Carbonic anhydrase catalyzes the conversion between the two compounds.

2.     Non-votilitle acid (aka fixed acid or metabolic acid):   Produced from [metabolism of carbohydrates, fats, and proteins] sources other than CO2, and is not excreted by the lungs. The nonvolatile acids are buffered with HCO3-, and excreted by the kidneys. Common nonvolatile acids in humans:  SOUP --> S-sulfuric acid, O-organic acids, U-uric acid, P-phosphoric acid. 

Ø  S _______________, _______________, _______________, _______________, _______________

Ø  O _______________, _______________, _______________, _______________, _______________

Ø  U _______________, _______________, _______________, _______________, _______________

Ø  P _______________, _______________, _______________, _______________, _______________

PATHOPHYSIOLOGY:  The kidneys maintain acid-base homeostasis by regulating the pH of the blood plasma. Gains and losses of acid and base must be balanced. Hydrogen ions are buffered by extracellular (e.g., bicarbonate, ammonia) and intracellular buffering agents (including proteins and phosphate).  The bicarbonate buffer system is the most important determinant of blood pH.  Kidney maintain HCO3− buffer by reabsorbing and synthesizing HCO3−.  Thus,
1.     In cases of H+ excess (i.e. acidemia):  HCO3− + H+ ⇌ H2CO3     

2.     In cases of H+ deficiency:  H2CO3 ⇌ HCO3− + H+

3.     Acid dissociation constant:  Ka = ([HCO3−] [H+]) / [H2CO3]

4.     Henderson-Hasselbalch equation: pH = pKa + log ([HCO3−] / [H2CO3])

An acid base nomogram for human plasma, showing the effects on the plasma pH when carbonic acid (partial pressure of carbondioxide) or bicarbonate occur in excess or are deficient in the plasma

By Huckfinne - Own work, Public Domain,


* Indicate primary disorder

TREATMENT:  Treat the underlying abnormalities, and the lungs and kidneys will restore the acid-base homeostasis.
Ø  RESPIRATORY ACIDOSIS:  Hypoventilation = LOW --> L-lung disease (e.g. pneumothorax, CODP),  O-opiates & anesthesia, W-weak  respiratory muscle (muscular dystrophy)

v  L _______________, _______________, _______________, _______________, _______________

v  O _______________, _______________, _______________, _______________, _______________

v  W _______________, _______________, _______________, _______________, _______________

Ø  METABOLIC ACIDOSIS WITH ↑ AG:  MUD PILES --> M-methanol, U-uremia, D-DKA, P-para-aldehyde, P-phenformin, I-INH, I-iron, L-lactic acidosis, E-ethylene glycol, S-salicyclates

v  M _______________, _______________, _______________, _______________, _______________

v  U _______________, _______________, _______________, _______________, _______________

v  D _______________, _______________, _______________, _______________, _______________

v  P _______________, _______________, _______________, _______________, _______________

v  I _______________, _______________, _______________, _______________, _______________

v  L _______________, _______________, _______________, _______________, _______________

v  E _______________, _______________, _______________, _______________, _______________

v  S _______________, _______________, _______________, _______________, _______________

Ø  METABOLIC ACIDOSIS WITH NORMAL AG:  Hyper Li+, K+, Ca2+, Mg2+, hypoalbuminemia, multiple myeloma

Ø  METABOLIC ACIDOSIS WITH ↓ AG: G-glue D-directly H-hit R-renal = GDHR --> G-glue, D-diarrhea, D-diuretics (K+-sparing and CA-I), H-hyperCl-, R-RTA

v  G _______________, _______________, _______________, _______________, _______________

v  D _______________, _______________, _______________, _______________, _______________

v  H _______________, _______________, _______________, _______________, _______________

v  R _______________, _______________, _______________, _______________, _______________

Ø  RESPIRATORY ALKALOSIS: Hyperventilation: HIGH --> H-high altitude, H-high fever, I-infection (e.g. pneumonia), I-ingestion (ASA, doxapram), G-gestation, H-hematoma of CNS

v  H _______________, _______________, _______________, _______________, _______________

v  I _______________, _______________, _______________, _______________, _______________

v  G _______________, _______________, _______________, _______________, _______________

v  H _______________, _______________, _______________, _______________, _______________

Ø  METABOLIC ALKALOSIS: A-anorexic D-diva H-hyperV-vomit = ADHV --> A-antacid use, D-diuretic use (contraction alkalosis from loop & thiazide), H-hypokalemia (intracellular shift), H-hyperaldosterone (↓ K+, ↑ HCO3-), V-vomiting (lose H+).

v  A _______________, _______________, _______________, _______________, _______________

v  D _______________, _______________, _______________, _______________, _______________

v  H _______________, _______________, _______________, _______________, _______________

v  V _______________, _______________, _______________, _______________, _______________

·       ELECTROLYTES DISORDERIntracellular ions (KCOM --> K-k+, C-ca2+, O-organic anion, M-mg2+).  Extracellular ions (Na+, Cl-, HCO3-).

HYPERCALCEMIA (normal 9-10.5 mEq/L):  Can be an asymptomatic laboratory finding, but a work up should be undertaken if it persists. 
Ø  PATHOPHYSIOLOGY:  Etiologies include H-high CALCIUM --> H-hyperparathyroidism (e.g. parathyroid hyperplasia, parathyroid adenoma/carcinoma, MEN, familial isolated hyperparathyroidism, familial hypocalciuric hypercalcemia), C-calcium supplementation, A-addison’s disease, A-acromegaly, A-aluminum intoxication, L-Li+ use (causes abnormal parathyroid gland function), C-cancer (see M-malignancy), I-intoxication with Vitamin D (hypervitaminosis, sarcoidosis and other granulomatous disease), I-immobilization (↑ osteoclast activation), U-upregulation of bone turnover (e.g. hyperthyroidism, Vitamin A intoxication, Paget’s disease, thiazide uses), M-milk-alkali syndrome, M-malignancy (bone metatasis-breast cancer, PTHrP-sqcc of lung or kidney cancer, pheochromocytoma, hematogic malignancy-multiple myeloma, lymphoma, leukemia).  ~90% of cases are account for by hyperparathyroidism and malignancy.

v  H _______________, _______________, _______________, _______________, _______________

v  C _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________

v  L _______________, _______________, _______________, _______________, _______________

v  C _______________, _______________, _______________, _______________, _______________

v  I  _______________, _______________, _______________, _______________, _______________

v  U _______________, _______________, _______________, _______________, _______________

v  M _______________, _______________, _______________, _______________, _______________

Micrograph of ovarian small cell carcinoma of the hypercalcemic type. H&E stain.

By Nephron - Own work, CC BY-SA 4.0,

Ø  PRESENTATION:  Symptoms are more common at level > 12.0 mg/dL.  Bones (fractures), stones (nephrolithiasis), groans (anorexia, N/V, constipation, PUD, pancreatitis), and psychic moans (fatigue, depression, confusion). 

Ø  DIAGNOSTIC EVALUATION:  H&P.  BMP.  Albumin.  Phosphate. PTH/PTHrP. 25-OH Vitamin D. TSH. SPEP.   EKG:  Short QT interval and widened T wave.

An Osborn wave, an abnormal EKG tracing that can be associated with hypercalcemia.

Ø  TREATMENT:   Initial therapy: IVF (many patients are dehydrated due to vomiting or renal defects), increasing salt intake (increased Na+ excretion by cause increased calcium excretion), and forced diuresis (after rehydration, furosemide given to permit urinary Ca2+ excretion).   Additional therapy: Bisphosphonates (taken up by osteoclasts and inhibit osteoclastic bone resorption; but relatively contraindicated in renal failure), calcitonin (induce uptake of Ca2+ into bone and inhibit renal Ca2+ reabsorption), glucocorticoids (used in hypervitaminosis D, sarcoidosis, hypercalcemia due to osteolytic malignancies [multiple myeloma, leukemia, Hodgkin's lymphoma, carcinoma of the breast], and dialysis.  Supplemental phosphate: prn to correct the hypophosphatemia. 

o   HYPOCALCEMIA:  Total calcium < 9 mEq/L.   

Ø  PATHOPHYSIOLOGY:  ~ ½ of the serum total calcium is bound to proteins (primarily albumin).  It is the unbound, or ionized, calcium that the body regulates. If a person has abnormal levels of blood proteins then the plasma calcium may be inaccurate.  Quick way to determine actual total Ca2+ in the face of hypoalbuminemia: Add 0.8 mg/dL to total Ca2+ for every 1 g/L reduction in albumin < 4 g/L. (i.e. measured total Ca2+ = 7; measured albumin = 2 --> corrected total Ca2+ = 8.6 [7+1.6]).  CAUSES OF HYPOCALCEMIA: 5P’s --> P-PTH absent (e.g. hereditary or acquired hypoparathyroidism, thyroidectomy, parathyroidectomy, hypomagnesemia, P-PTH ineffectiveness (e.g. CRF, absent of active Vitamin D), P-pseudohypoparathyroidism (condition caused by resistance to PTH causing hypocalcemia, hyperphosphatemia, but the PTH level is appropriately high; Type 1a [aka Albright's hereditary osteodystrophy], has a characteristic phenotypic appearance including short fourth and fifth metacarpals and a rounded facies; Type 1b lacks the physical appearance of type 1a, but is biochemically similar; pseudopseudohypoparathyroidism describes a condition where the individual has the phenotypic appearance of type 1a, but is biochemically normal), P-phosphate excess (ARF, tumor lysis syndrome, rhabdomyolysis), P-pancreatitis (from fat saponification), P-poor nutrition (low Ca2+ or Mg2+ intake).

v  P _______________, _______________, _______________, _______________, _______________

v  P _______________, _______________, _______________, _______________, _______________

Ø  PRESENTATION:  Early symptoms:  Perioral tingling and 'pins and needles' sensation over the hands and feet.  Later symptoms:  Abdominal cramp, hyperactive DTR, tetany (Trousseau sign-inflate the BP cuff above systolic produces carpal spasm; Chvostek's sign-tap facial nerve produces facial spasms), and life-threatening laryngospasm or cardiac arrhythmias.

A hand being held similarly to Trousseau's sign.

By Huckfinne - Own work, Public Domain,

Drawing of a normal ECG tracing (sinus rhythm) with waves, segments, and intervals labeled. The QT interval is marked by the blue line at bottom.

By Created by Agateller (Anthony Atkielski), converted to svg by atom. - SinusRhythmLabels.png, Public Domain,

Acquired long QT syndrome.

By Created by Agateller (Anthony Atkielski), converted to svg by atom. - SinusRhythmLabels.png, Public Domain,

12-lead ECG of Torsades de Pointes (TdP) in a 56-year-old white female with low blood potassium (2.4 mmol/L) and low blood magnesium (1.6 mg/dL.)

Jer5150 - Own work, CC BY-SA 3.0,

An ECG of a person with hypocalcemia

By User:Drj -, CC BY-SA 4.0,

Ø  DIAGNOSTIC EVALUATION:  BMP. Mg2+ level. PTH.  Albumin. Calcitonin.  EKG: Prolonged QTc and ST interval

Ø  TREATMENT:  Underlying disorder. Ca2+ supplements:  Calcium & vitamin-D PO or calcium gluconate IV if severe.

o   HYPERKALEMIA:   Normal range 3.5-5 mEq/L. K+ is the most abundant intracellular cation, and critically important for the maintenance of cellular membrane potential.  The regulation of serum K+ is done by the kidney’s distal tubule and collecting duct.  There, in the presence of aldosterone, Na+ is reabsorbed and K+ is excreted.

Ø  PATHOPHYSIOLOGY: ↑ extracellular K+ levels result in depolarization of the membrane potentials of cells. This depolarization opens some voltage-gated sodium channels, but not enough to generate an action potential. After a short while, the open sodium channels inactivate and become refractory, increasing the threshold to generate an action potential. This leads to the impairment of neuromuscular, cardiac, and gastrointestinal organ systems. Hyperkalemia develops when there is excessive production (oral intake, tissue breakdown) or ineffective elimination of potassium (e.g. in aldosterone deficiency or impair renal excretion).  Causes include:  STAR --> S-spurious (pseudohyperkalemia due to excessive leak of K+ from cells due to hemolysis during venipuncture, delay processing of blood specimen, erythrocytosis-Hct > 55%,   thrombocytosis >1,000,000/mm³, or leukocytosis > 100 000/mm³), S-spironolactone, T-TMP, T-tacrolimus, A-amiloride, A-ACE-I, A-ARB and NSAIDs use (these med ↓ renal excretion), A-adrenal insufficiency (i.e. A-addison’s disease), A-aldosterone deficiency, R-RTA type IV (due to aldosterone deficiency), R-renal insufficiency, R-release from cell (e.g. R-rhabdomyolysis, extreme exercise, hemolysis, tumor lysis syndrome, massive blood transfusion, acidemia, succinylcholine use, beta-blocker use, hypoinsulinemia, and diogixin overdose).  Associated condition: Hyperkalemic periodic paralysis:  A rare hereditary condition in which mutation of the SCN4A gene causes episodic muscle weakness and spasms associated with transient hyperkalemia (can be precipitated by exercise, fasting, and stress).

v  S _______________, _______________, _______________, _______________, _______________

v  T _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________

v  R _______________, _______________, _______________, _______________, _______________

Ø  PRESENTATION:  Nonspecific N/V, malaise, palpitations, muscle weakness, flaccid paralysis, areflexia, intestinal colic.  More specific symptoms depends on etiology:  SOB (may indicate metabolic acidosis).   Combination of abdominal pain, hypoglycemia and hyperpigmentation (may be signs of Addison's disease). Uremic syndrome (CRF).

Ø  DIAGNOSTIC EVALUATION:  H&P:  Medications use.  Kidney disease.  Repeat BMP: Verify hyperK+, check renal function. Creatine kinase and cortisol level.    EKG (change begins when >6.5 mg/dL):  Peaked T waves, prolonged PR interval, widened QRS segment, loss of P waves that can progress to sine waves, and ventricular fibrillation/cardiac arrest.  Renal ultrasound: Rule out renal disease.

Electrocardiography showing precordial leads in hyperkalemia.

By Mikael Häggström - Own work, Public Domain,

An ECG of a person with a potassium of 5.7 showing large T waves and small P waves.

By Mikael Häggström - Own work, Public Domain,

Ø  TREATMENT:   C-cure BIG K = CBIGK --> C-calcium gluconate 10% (give first to stabilize cardiac membrane; preferably give through a central venous catheter as the calcium may cause phlebitis),  b-agonist (e.g. albuterol) or B-bicarbonate 45 mEg or I-insulin 10-15U and G-glucose IV  (these meds shift of K+ into cells), K-kayexalate (a resin that binds K+ within the intestine and removes it by defecation).  Loop and thiazide diuretics: Remove K+ by urination.  Dialysis: For refractory or severe cases.

v  C _______________, _______________, _______________, _______________, _______________

v  B _______________, _______________, _______________, _______________, _______________

v  I _______________, _______________, _______________, _______________, _______________

v  G _______________, _______________, _______________, _______________, _______________

v  K _______________, _______________, _______________, _______________, _______________


Ø  PATHOPHYSIOLOGY:  ↓ extracellular K+ level result in hyperpolarization of the resting membrane potential. As a result, a greater than normal stimulus is required for depolarization of the membrane in order to initiate an action potential. However, in the heart, it causes myocytes to become hyperexcitable. Hypokalemia develops when there is insufficient intake or excessive loss (e.g. vomit, diarrhea).  Causes include:  STAR --> S-shift T-transcellularly (due to AEI --> Alkalosis, Epinephrine, Insulin), A-aldosterone excess (due to renal artery stenosis, adrenal tumor, licorice ingestion), A-abdominal/GI loss (due to vomit, diarrhea), R-renal loss (due to loop/thiazide diuretics, amphotericin B, DKA polyuria, aldosterone excess).  Associated condition: Hypokalemic periodic paralysis:   A rare autosomal dominant condition in which mutations of the CACNA1S or SCN4A gene causes periodic muscle weakness or paralysis associated with transient hypokalemia (can be precipitated by strenuous exercise followed by rest, high carbohydrate meals, sudden changes in temperature and even excitement, noise or flashing lights).  Bartter’s syndrome:  Mutations of genes encoding ion-transporter  in the thick ascending LOH that result in defective renal Na+ reabsorption.  This leads to the loss of Na+, and thus, fluid in the urine.  The resultant hypovolemic state activates the RAAS causing ↑ K+ and H+ excretion -->  hypokalemia, metabolic acidosis, ↑ renin & aldosterone levels, and a normal-low BP (due to volume loss).  Gitelman syndrome:  Mutations in the SLC12A3 gene resulting in a loss of function of the thiazide-sensitive Na+/Cl--co-transporter in the DCT. Thus symptoms are identical to those of patients on thiazide diuretics (hypochloremic metabolic alkalosis, hypokalemia, hypomagnesemia, and hypocalciuria).

v  S _______________, _______________, _______________, _______________, _______________

v  T _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________

v  R _______________, _______________, _______________, _______________, _______________

Ø  PRESENTATION:  Muscular weakness (including the diaphragm), myalgia, muscle cramps, and constipation (disturbed smooth muscles function), flaccid paralysis, hyporeflexia, and tetany may result.

Ø  DIAGNOSTIC EVALUATION: H&P.  Urine potassium level: Distinguish renal from GI loss.  ECG: Flattened T waves, U waves, ST segment depression, and prolonged QT interval.

Ø  TREATMENT:  Treat the underlying disorder (e.g. diarrhea) and correct hypomagnesemia.  K+ supplement:  PO or IV (e.g. NS with 20-40 mEq KCl/).  K+ IV solution should be at most 60 mEq/L and admistered no faster than 20 mEq/hour to avoid ventricular tachycardias.  Infusion via central line is encouraged to avoid phlebitis at the peripheral line.  Potassium-sparing diuretic (e.g. spironolactone):  For difficult or resistant cases. 

An ECG in a person with a potassium level of 1.1 meq/l showing the classical changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval.

By James Heilman, MD - Own work, CC BY-SA 3.0,

o   HYPOMAGNESEMIA:   Normal 1.7-2.3 mEq/L.

Ø  PATHOPHYSIOLOGY:  Serum magnesium is not an appropritate indicator of  the total amount of available magnesium because only 1% of total body Mg2+ reside in the extracellular fluid (most are found in bone). Most of the serum magnesium is bound to chelators, (i.e. ATP, ADP, proteins and citrate). The kidneys regulate serum magnesium through tubular reabsorption and excretion at the LOH. Hypomagnesemia causes concurrent hypokalemia (60% of cases) and hypocalcemia (40%) through inhibition of Na+/K+-ATPase and PTH release, respectively.  Causes include: MAGnesium --> M-malnutrition (e.g. hospitalization, alcoholism), M-malabsorption (aka GI losses), A-aldosterone excess, A-antibiotic use (e.g. aminoglycoside), A-amphotericin B use, G-GI losses (IBD, Whipple’s disease, celiac disease). Other: Diuretics use, pancreatitis, DKA.

v  M _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________

v  G _______________, _______________, _______________, _______________, _______________

Ø  PRESENTATION:  Weakness, muscle cramps, cardiac arrhythmia, and CNS  irritability (tremors, athetosis, nystagmus, confusion, disorientation, hallucinations, depression, and seizures).  Some symptoms are related to concurrent hypocalcemia and hypokalemia.

Ø  DIAGNOSTIC EVALUATION:  Mg2+, K+, Ca2+ level.  ECG:  Prolonged QT interval.

Ø  TREATMENT:  IV or PO Mg2+ supplement.  HypoK+ and hypoCa2+ will not correct without Mg2+ correction.

o   HYPERNATREMIA:  Normal serum sodium 135-148 mEq/L.   Severe symptoms usually due to acute hypernatremia > 158 mEq/L.

Ø  PATHOPHYSIOLOGY: The most common cause of hypernatremia is dehydration:  Due to inadequate intake of water (often in elderly or disabled patients), inappropriate excretion of water (due to medications-diuretics or lithium, N/V, polyuria-DKA or diabetes insipidus), or sequestration of bodily fluid (due to edema, ascites)  Others causes:  Intake of a hypertonic fluid (due to IVF resuscitation, seawater ingestion), Mineralcorticoid excess (e.g. Conn's syndrome or Cushing's Syndrome).

Ø  PRESENTATION:  Thirst, lethargy, weakness, irritability, seizures and coma.  Mostly neurologic symptoms as Na+  is the primary determinant of serum osmolality.  As serum osmolality ↑, water moves out of brain cells --> brain shrink.

Ø  DIAGNOSTIC EVALUATION: H&P.  Measure UOP and urine osmolality: A minimal volume (~ 500 mL/d) of maximally concentrated urine (> 400 mOsm/kg) suggests adequate renal response without adequate free water replacement.

Ø  TREATMENT:  Treat underlying cause.  The cornerstone of treatment is administration of free water to correct the relative water deficit. Correction of hypernatremia should occur gradually over 48-72 hours.   Rapid correction causes water to flow into brain cells and causes  cerebral edema, which can lead to seizures, permanent brain damage, or death.

Management of hypernatremia

By en:User:HarishV -, CC BY-SA 3.0,

o   HYPONATREMIA:  < 135 mEq/L.

Ø  PATHOPHYSIOLOGY:  Hyponatremia is best considered in conjunction with the person's plasma osmolarity and ECF volume status.  Most cases of hyponatremia are associated with reduced plasma osmolarity. In fact, the vast majority of adult cases are due to increased ADH secretion (not necessarily SIADH), which causes retention of water, but not salt.  WORK UP OF AND CLASSIFICATION:

Ø  PRESENTATION:  Mainly neurologic symptoms as hyponatremia causes osmotic shift of water from the plasma into the brain cells. N/V, HA, malaise, confusion, diminished reflexes, convulsions, stupor or coma.

Ø  TREATMENT:  Treat underlying disorder.  Hypervolemic hyponatremia: Water intake restriction. Hypovolemic hyponatremia:  Give IV isotonic saline. Euvolemic hyponatremia:  Water intake restriction and add demeclocycline to inhibit ADH.  Note that sudden correction of hyponatremia leads to central pontine myelinolysis, characterized by quadriplegia and pseudobulbar palsy. 

o   HYPERPHOSPHATEMIA (normal 2.7-4.5 mg/dL):  ETIOLGY:  Commonly seen in chronic renal failure. Often, there is concomitant hypocalcemia due to precipitation of phosphate with the calcium in tissues.  PRESENTATION:  Ectopic calcification, secondary hyperparathyroidism, and renal osteodystrophy. TREATMENT:  Phosphate binders (e.g. sevelamer) and dietary restriction of phosphate.

o   HYPOPHOSPHATEMIA (< 2.7 mg/dL): 

Ø  PATHOPHYSIOLOGY:  Hypophosphatemia is often uncover in Refeeding Syndrome, especially in alcoholics.  Refeeding syndrome:  After a period of starvation, food intake causes a demand for phosphate in cells due to the action of phosphofructokinase (attaches phosphate to glucose to begin metabolism), and during production of ATP when cells are fed and recharge their energy supplies. Hypophosphatemia is caused by the following three mechanisms:

1.     Inadequate intake:  Alcoholics, malabsorption syndrome, use of phosphate binders (e.g. sucralfate, antacids).

2.     Increased excretion:  Hyperparathyroidism, diuretics use.

3.     Shift from extracellular to intracellular space:  Seen in treatment of DKA, refeeding, short-term increases in cellular demand (e.g., hungry bones syndrome), and acute respiratory alkalosis (alkalemic condition moves phosphate out of the blood into cells).

Ø  PRESENTATION:  Muscle dysfunction and weakness (including diplopia, low cardiac output, dysphagia, and respiratory depression), mental status changes (irritability, confusion, delirium, coma), WBCs dysfunction (↑ infections), instability of cell membrates due to low ATP levels (may cause rhabdomyolysis and hemolytic anemia).

Ø  TREATMENT:  Potassium phosphate PO or IV supplementation.



·       The cloaca is the common cavity into which the intestinal, genital, and urinary tracts open.  It is partitioned into 2 pieces:  1) anterior which becomes the urogenital sinus 2) posterior which becomes the anorectal canal.

·       The bladder develops from the upper end of the urogenital sinus, which is continuous with the allantois.

·       The allantois degenerates and forms the urachus (aka the median umbilical ligament), which connects the bladder to the umbilicus.  Urachal sinus: Persistent patency of the urachus causing urine drainage from the umbilicus.

·       The trigone of the bladder is formed by the incorporation of the lower end of the mesonephric ducts into the posterior wall of the urogenital sinus.

Cloaca of human embryo from twenty-five to twenty-seven days old.

By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below) Gray's Anatomy, Plate 992, Public Domain,

Bladder location and associated structures in the male

 By Created by US government agency National Cancer Institute -, Public Domain,



Trigone : A triangular shaped area on the postero-inferior wall of the bladder, where the ureters enter the bladder. The urethra exits at the lowest point of the triangle of the trigone.
Apex: Connected to the umbilical cord by the median umbilical ligament.   
Neck: Connected to the pubic bone by the pubovesical ligament (women) or puboprostatic ligament (men).
·       LAYERS OF THE BLADDER WALL:  Inner to outer

1.     Mucosa:  Transitional epithelium & lamina propria.

2.     Detrusor muscle: Consists of an inner and outer longitudinal layer and a middle circular layer of smooth muscle

3.     Fibrous adventitia and the visceral peritoneum: Lie on superior surface


1.     Detrusor muscle:  Involuntary smooth muscle

2.     Internal urethral sphincter: Involuntary smooth muscle. It is the primary muscle for constricting the release of urine.

3.     External urethral sphincter: Voluntary skeletal muscle to control the flow of urine through the urethra.

Anatomy of the male bladder, showing transitional epithelium and part of the wall in a histological cut-out.

Vertical section of bladder wall.

By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below) Gray's Anatomy, Plate 1141, Public Domain,

Layers of the urinary bladder wall and cross section of the detrusor muscle.

Public Domain,



1.     Sympathetic control:  Hypogastric nerve (from the intermediolateral cell column T11-L1) release norepinephrine, which relaxes detrusor muscle (via b3-adrenergic receptor) and contracts internal urethral sphincter (via a1-adrenergic receptor).  These INHIBIT MICTURITION.

2.     Parasympathetic control: Pelvic nerve (from parasympathetic nuclei of S2-S4) release ACh, which contracts detrusor muscle (via M3 receptor).  This ALLOWS MICTURITION.

3.     Voluntary control: Pudendal nerve (from S2-S4) contracts external sphincter. 


·      BLADDER SPHINCTER DYSSYNERGIA:  A condition in which the contraction of the bladder musculature is not coordinated with the relaxation of the sphincter during voiding. Pathophysiology:  A consequence of neurological condition such as spinal injury or multiple sclerosis.  Presentation:  Daytime and night time wetting and often have frequent UTIs.  Constipation and encopresis are often associated with this condition.  Diagnostic evaluation:  EMG trace:  The tracing shows both the pressure and flow phenomena.   Cystography:  Irregular appearance of the bladder outline due to muscular contraction against the unrelaxed bladder sphincter.

Urodynamic trace of detrusor sphincter dyssynergia

By Warbeck~enwiki - Own work by the original uploader, Public Domain,

·      NEUROGENIC BLADDER:  Urinary bladder dysfunction due to disease of the CNS or peripheral nerves involved in the control of micturition.

o   PATHOPHYSIOLOGY:  Associated with spinal cord diseases, injuries, neural tube defects including spina bifida, brain tumors and other diseases of the brain and peripheral nerve diseases. It is a common complication of major surgery in the pelvis, such as for removal of sacrococcygeal teratoma and other tumors.

o   TREATMENT:  Neurogenic bladder usually causes difficulty or full inability to pass urine without use of a catheter or other method. Consequently most treatments involve creation of a stoma that is continent and readily accepts a catheter. Function of the stoma may be augmented by periodic injections of botulinum toxin to relax one of the two sphincters involved in normal urination.


o   PATHOPHYSIOLOGY:  Continence and micturition involve a balance between urethral closure and detrusor muscle activity. Urethral pressure normally exceeds bladder pressure and intraabdominal pressure increases are transmitted to both urethra and bladder equally, resulting in urine remaining in the bladder.  TYPES:

Voiding dysfunction

By ColnKurtz - Own work, CC BY-SA 4.0,

o   DIAGNOSTIC EVALUATION:  H&P:  History of pattern of urine leakage, medication use, recent surgery, and illness.  Exam for signs of GU tumors, stool impaction, and poor reflexes or sensations.  PVR (postvoid residual): Elevated with overflow incontinence.  UA:  Rule out infection, GU stones.   Stress test:  Patient coughs vigorously as the doctor watches for loss of urine. Cotton swab test: Insert cotton swab into urethra, then patient strains as if urinating.  The change in cotton swab angle > 30 degree occurs with hypermobile bladder neck, which is associated with stress incontinence.  Cystometrogram: Measure bladder and sphincter tone as bladder is filled.  US:  Visualize the kidneys, ureters, bladder, and urethra. Cystoscopy.  

·       BLADDER CANCER:  The most common (90%) type of bladder cancer begins is transitional cell carcinoma (TCC).  Less common is squamous cell carcinoma, adenocarcinoma, and sarcoma.

EPIDEMIOLOGY:  US incidence: 47,000/yr (male; 4th most common) and 16,000/yr (women; 9th most common).    
PATHOPHYSIOLOGY:  Risk factors for bladder TCC:  Exposure to environmental carcinogens including cigarette smoking (thought to cause 50% of bladder cancers in male patients), benzidine (textile/dye industry),  hydrocarbons and petroleum-based chemicals (auto mechanics),  drugs (cyclophosphamide and phenacetin).   are known to predispose to bladder TCC. Risk factor for squamous cell carcinoma of the bladder: Chronic bladder irritation (infection, bladder stones, catheters, bilharzia/schistosomiasis). One reason for its higher incidence in men is that the androgen receptor, which is much more active in men than in women, plays a major part in the development of the cancer.
PRESENTATION:  Gross hematuria (most common), frequency, urgency, and dysuria.
DIAGNOSTIC EVALUATION:  UA: Hematuria.  Urine cytology (look for dysplastic cells) and transurethral cystoscopy (visualize lesion with biopsy):  Constitute the gold standard of diagnosing bladder cancer.  CT/MRI: Work up metastasis as TCCs are often multifocal, with 30-40% of patients having a more than one tumour at diagnosis. 

Location of bladder cancer

Transitional cell carcinoma of the bladder. The white in the bladder is contrast.

By James Heilman, MD - Own work, CC BY-SA 4.0,

Bladder wall thickening due to cancer.

Bladder tumor in FDG PET due to the high physiological FDG-concentration in the bladder, furosemide was supplied together with 200 MBq FDG. The uptake cranial to the lesion is a physiological uptake in the colon.

By Hg6996 - Own work, Public Domain,

Histopathology of urothelial carcinoma of the urinary bladder. Transurethral biopsy. H&E stain.


Diagram showing the T stages of bladder cancer

By Cancer Research UK - Original email from CRUK, CC BY-SA 4.0,

Flow chart of the Bladder Cancer Treatment Guide

TREATMENT:  The treatment of bladder cancer depends extent of spread beyond the bladder mucosa.
Ø  CIS (carcinoma in-situ): Intravesicular chemotherapy.

Ø  Superficial cancers: Transurethral resection or BCG instillation (effectiveness ↓ with concurrent statins use) or intravesicular chemotherapy.

Ø  Larger, infiltrating tumors:  Combination of chemotherapy and radiation.  Cystectomy. 

Ø  Distantant metastasis: Chemotherapy.



EMBRYOLOGY: A composite organ made up of glandular and non-glandular components arising from the condensation of mesenchyme, urethra and Wolffian ducts.  It arises in the 9th week of embryonic life.  Skene's glands found in many females are homologous to the prostate gland in males.


Lobes of prostate

Public Domain,

Zones of prostate

Prostate with seminal vesicles and seminal ducts, viewed from in front and above.

Micrograph of benign prostatic glands with corpora amylacea. H&E stain.

By Nephron - Own work, CC BY-SA 3.0,

PHYSIOLOGY:  The prostate secretes a clear, slightly alkaline (pH 7.29) fluid that constitutes 10-30% of the volume of the semen. The protein content is < 1% and includes acid phosphatase, citric acid, fibrinolysin, PSA, proteolytic enzymes, and zinc.  Zinc stabilizes the DNA-containing chromatin in the sperm cells. A zinc deficiency may result in lowered fertility because of increased sperm fragility.

PATHOLOGY: Prostatitis, BPH, and Prostate cancer.

·       PROSTATITIS:  According to the 1999 NIH Classification, there are four categories of prostatitis:

·       BPH (BENIGN PROSTATIC HYPERPLASIA):  Hyperplasia of prostatic stromal and epithelial cells.   

o   EPIDEMIOLOGY:  Prevalence: 2.7% for men aged 45-49, increasing to 24% by the age of 80 years.

PATHOPHYSIOLOGY:  Androgens play a permissive role in BPH. This means that androgens have to be present for BPH to occur, but do not necessarily directly cause the condition. This is supported by the fact that castrated boys do not develop BPH when they age and administering exogenous testosterone is not associated with a significant increase in the risk of BPH symptoms. Dihydrotestosterone (DHT), a metabolite of testosterone is a critical mediator of prostatic growth. DHT is synthesized in the prostate from circulating testosterone by the action of the enzyme 5α-reductase, type 2. This enzyme is localized principally in the stromal cells.  DHT can act in an autocrine fashion on the stromalie cells or in paracrine fashion by diffusing into nearby epithelial cells. In any case, DHT causes hyperplasia of these cell types, which results in the formation of large, fairly discrete nodules in the periurethral region of the prostate. When sufficiently large, the nodules compress the urethral canal to cause partial, or sometimes virtually complete, obstruction of the urethra which interferes the normal flow of urine.  BPH is not considered to be a premalignant lesion.

Two-panel drawing shows normal male reproductive and urinary anatomy and benign prostatic hyperplasia (BPH). Panel on the left shows the normal prostate and flow of urine from the bladder through the urethra. Panel on the right shows an enlarged prostate pressing on the bladder and urethra, blocking the flow of urine.

By Unknown - National Cancer Institute, AV Number: CDR462221, Public Domain,

o PRESENTATON: 2 categories of symptoms: 1) Obstructive: Hesitancy, intermittency, incomplete voiding, weak urinary stream, and straining 2) Irritative: Frequency, urgency, and nocturia. Incomplete voiding results in stasis of bacteria in the bladder residue and an increased risk of urinary tract infections, bladder stones, and renal failure from obstructive uropathy.

o DIAGNOSTIC EVALUATION: Rectal exam: May reveal a markedly enlarged prostate. PSA: Rule out prostatic malignancy. If elevated further investigations such as PSA density and PSA free percentage are indicated. US/CT: Exam the testicles, prostate and kidneys to rule out malignancy and hydronephrosis.

Digital rectal examinations

Micrograph showing nodular hyperplasia (left off center) of the prostate from a transurethral resection of the prostate (TURP).

By Nephron - Own work, CC BY-SA 3.0,

Benign prostate hyperplasia: Stromal hyperplasia.

TREATMENT:  Lifestyle:  ↓ nighttime fluid intake, ↓ alcohol and caffeine consumption, and follow timed voiding schedules.  Medications:  α1-adrenergic receptor antagonists (doxazosin, terazosin, alfuzosin tamsulosin):   Relax smooth muscle in the prostate and the bladder neck, and provide symptomatic relief of BPH symptoms. 5α-reductase inhibitors (finasteride and dutasteride): Reduce DHT, thus slowing BPH progression and delay the need for surgery.  Surgery: TURP (transurethral resection of prostate) or open prostatectomy is indicated for moderate to severe BPH when medical therapy failed.  More novel methods involve the use of laser or microwave to  reduce the size of an enlarged prostate, while minimizing damage to normal tissue. 
SUMMARY OF BPH: BPH --> B-bladder trabeculation is seen as a response to urinary obstruction, P-periurethral TZ  grows throughout life leading to H-hyperplasia of both glandular and fibromuscular stromal elements, eventually H-hydroureter and H-hydronephrosis are seen secondary to urinary obstruction.
Ø  B _______________, _______________, _______________, _______________, _______________

Ø  P _______________, _______________, _______________, _______________, _______________

Ø  H _______________, _______________, _______________, _______________, _______________

  PATHOPHYSIOLOGY:  Risk factors:  Age (the primary risk factor as prostate cancer is uncommon in men < 45, but becomes more common with advancing age, autopsy studies have found prostate cancer in 30% of men in their 50’s, and in 80% of men in their 70’s), genetics (BRCA1 and BRCA2 that are important risk factors for ovarian cancer and breast cancer in women have also been implicated in prostate cancer),  race (most commonly affects black men), diet (high trans fatty acids, low vitamin E, low omega-3 fatty acids, low antioxidant such as selenium and lycopene, and low vitamin D may increase the risk of developing prostate cancer), lifestyle (sedentary and lower exposure to UV light), medications (daily use of anti-inflammatory medicines [e.g. aspirin, ibuprofen, or naproxen] and statins may decrease prostate cancer risk).  Others risks:  Prostatitis, obesity, and ↑ blood levels of testosterone.  

PRESENTATION:  Usually asymptomatic in early stages and often initially diagnosed during the workup for an elevated PSA noticed during a routine checkup.  Possible symptoms: Similar to BPH and include obstructive symptoms (hesitancy, intermittency, incomplete voiding, weak urinary stream, and straining), irritative (frequency, urgency, nocturia, dysuria, hematuria).  Prostate cancer may also cause sexual dysfunction (erectile dysfunction or painful ejaculation). Advanced prostate cancer can metastasize, most often in vertebrae, pelvis or ribs, causing back pain. Prostate cancer in the spine can also compress the spinal cord, causing leg weakness and urinary and fecal incontinence.
DIAGNOSTIC EVALUATION:  H&P.  PSA:  Markedly elevated total PSA (normal <4ng/mL), but free PSA is low due to binding with a-anticymotrypsin.  Also used to monitor response to therapy.  Cystoscopy: Rule out bladder cancer.  Transrectal US:  Visualize the prostate for nodules.   Prostate biopsy (the only definitive test):  Normal prostate are replaced by irregular glands and clumps of cells.  Tumor markers:  Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin of maligant cells.  CXR/CT/MRI:  Look for metastasis.  Bone scans:  Reveal osteoblastic appearance due to increased bone density in the areas of bone metastisis.  New molecular test being studied for the early detection of prostate cancer include test that detects the presence of PCA3 mRNA in urine or EPCA-2 in the serum.  PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells. PCA3 is not a replacement for PSA but an additional tool to help decide if, in men suspected of having prostate cancer, a biopsy is really needed. EPCA-2 (early prostate cancer antigen) may alert men if they have prostate cancer and how aggressive it will be.   Gleason scoring for prostate cancer:  Sum the scores (from 1 to 5) of the two most dysplastic samples; with 10 being the highest grade and 2 the lowest grade possible.

A diagram of prostate cancer pressing on the urethra, which can cause symptoms.

By Cancer Research UK - Original email from CRUK, CC BY-SA 4.0,

Prostate cancer.

Sclerosis of the bones of the thoracic spine due to prostate cancer metastases (CT image)

Sclerosis of the bones of the thoracic spine due to prostate cancer metastases (CT image)

Sclerosis of the bones of the pelvis due to prostate cancer metastases

·       PROSTATE CANCER:  An adenocarcinoma most commonly arises in the peripheral zone. Prostate cancer most commonly metastasizes to the bones, lymph nodes, rectum, and bladder.

EPIDEMIOLOGY:  Worlwide, it is least common in South and East Asia, more common in Europe, and most common in the United States.   In the US, it is the most common cancer in men and the second leading cancer death, with annual incidence of 230,000.  Blacks > whites > Asians.  It commonly strikes men > 50 y/o. 

New cases and deaths from prostate cancer in the United States per 100,000 males between 1975 and 2014

By NIH -, Public Domain,

Prostate needle biopsy.

Micrograph of prostate adenocarcinoma, acinar type, the most common type of prostate cancer. Needle biopsy, H&E stain.

By Nephron - Own work, CC BY-SA 3.0,

Micrograph showing a prostate cancer (conventional adenocarcinoma) with perineural invasion. H&E stain.

TREATMENT:  Since prostate cancer is a disease of older men and it is slow to progress, many patient will die of other causes before prostate cancer can spread or cause symptoms.  Thus, treatment choice is based on the aggressiveness of the tumor.   Diet: There is some medical evidence for the effectiveness lycopene (found in tomatoes, watermelons, pink grapefruits, papaya, and guava) in controlingl the growth of prostate cancer cells.  ↓ fats and ↑omega-3 fatty acids intake have also been shown to ↓ the risk..  Watchful waiting and active surveillance:  For elderly patient with low-grade tumors or when the risks of surgery, radiation therapy, or hormonal therapy outweigh the possible benefits.  Surgery:  Radical prostatectomy is effective for early stage prostate cancer that have not spread beyong the prostate, or for cancer which has failed to respond to radiation therapy.  It is combined with adjuvant radiation therapy in the event of positive margins or locally advanced disease.  Its side effects may include nerve damage resulting in urinary incontinence and impotence.  Radiation therapy:  Can use external beam radiation (given over several weeks with daily visit to a radiation therapy center) &/or brachytherapy (placement of radioactive material such as iodine-125 or palladium-103 directly into the tumor). Radiation may be used instead of surgery for early cancers or in advanced cases to treat painful bone metastases. Side effects of radiation therapy include diarrhea and rectal bleeding (radiation proctitis),  urinary incontinence, impotence, and higher risk of later developing colon cancer and bladder cancer. Hormonal therapy:  Uses medications (e.g. antiandrogens such as flutamide and cyproterone acetate which directly block the actions of testosterone/DHT within prostate cancer cells or GnRH-agonist such as leuprolide which suppresses LH) or surgery (orchiectomy to get rid of the source of testesterone).  Hormonal therapy often causes prostate cancer to stop growing and even shrink. However, cancers typically become resistant after one to two years. Therefore, it is often used only in metastatic disease. 
PREVENTION:  Screening for prostate cancer is controversial because it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments.  Current guideline recommends annual PSA testing and DRE beginning at age 50 (begin at age 40 for African-American men, men with a family history of prostate cancer).  Biopsy is recommended if DRE is positive or PSA ≥ 4 ng/mL.
SUMMARY OF PROSTATE CANCER:  PSA --> P-peripheral zone is where most cancer aris, P-PSA (↑ total PSA, ↓ free PSA from binding to a-antichymotrysin), P-PAP (prostatic acid phosphatase) ↑ when tumor penetrate the prostatic capsule, S-spread to bone leading to A-alkaline phosphatase ↑, A-androgen stimulation is essential for tumorigenesis.
v  P _______________, _______________, _______________, _______________, _______________

v  S _______________, _______________, _______________, _______________, _______________

v  A _______________, _______________, _______________, _______________, _______________