RENAL (5%)

Question 1

HYPERKALEMIA

Answer 1

hyperkalemia = higher than normal potassium levels in the blood

normal K+ range = 3.5 - 5.0

Hyperkalemia = > 5.0 or 5.5 mEq/L

Levels > 7.0 can be life-threatening due to its effect on heart muscle

Total body potassium can be split into intracellular and extracellular

o Extracellular = Intravascular space + Interstitial space
⦁ Intravascular = in blood vessels + lymphatic vessels
⦁ Interstitial = space between cells where other proteins and carbohydrate chains are found

o Intracellular = within the cell

MAJORITY OF K+ = INTRACELLULAR (98%) = 150mEq/L
- about 2% = extracellular = 4.5 mEq/L

o INTERNAL POTASSIUM BALANCE
⦁ K+ has a charge, so having much more K+ in the cells creates an electrochemical gradient, called the Internal Potassium Balance, which is maintained by the Na / K pump - pumps 3 Na+ out for every 2 K+ in

⦁ There are also potassium leak channels and inward rectifying channels that are scattered throughout the membrane

⦁ This electrochemical gradient is VERY IMPORTANT for setting the resting membrane potential of excitable cell membranes = needed for normal contraction of SMOOTH, CARDIAC + SKELETAL MUSCLES

o EXTERNAL POTASSIUM BALANCE
= potassium that you get externally through diet daily
- daily basis = typically get 50-150mEq/L = WAYY more than the extracellular K+ level of 4.5 mEq/L
⦁ so body has to excrete most of what it takes in = KIDNEYS - excreted via urine. Small amount of K+ is excreted via GI (poop) and sweat too

HOW DO YOU GET HYPERKALEMIA IN THE BLOOD?
1) decreased potassium excretion via kidneys = external balance shift
⦁ kidney failure / acute kidney injury
⦁ hypoaldosteronism (adrenal insufficiency)
⦁ drugs: ACEI / ARBs / Potassium-sparing diuretics

KIDNEY FAILURE

• potassium is normally freely filtered out of blood and into urine via glomerulus
• about 67% of K+ is reabsorbed in proximal convoluted tubule
• additional 20% reabsorbed in thick ascending limb
• distal tubule + CT can then either secrete or reabsorb remaining 13% depending on what the body needs
• ALDOSTERONE increases Na channels for Na to be reabsorbed and increases K channels for K to be excreted, as well as Na/K pumps
• Hypoaldosteronism (ADDISON’S)–> hyperkalemia

or increased potassium intake = external balance shift
⦁ IV fluids - rapid, excessive intake = iatrogenic cause

2) too much potassium moving out of cells and into interstitium + blood = internal balance shift
⦁ insulin deficiency (type I DM)
⦁ acidosis
⦁ beta adrenergic antagonists (beta blockers)
⦁ alpha agonists
⦁ succinylcholine - causes K efflux from muscles
⦁ hyperosmolarity
⦁ cell lysis
⦁ exercise

TYPE I DM

• after eating, glucose increases in the blood, so insulin is released. Insulin binds to cells and stimulates the uptake of glucose into cells
• insulin increases the activity of the Na / K pump - pulls potassium into cells / pulls sodium out of cells
• people with Type I DM don’t make insulin, so if they eat a meal, especially high in potassium, and don’t take insulin –> don’t have increased potassium intake into cells, so potassium sits in blood –> hyperkalemia

ACIDOSIS

• higher concentration of hydrogen ions in blood = low blood pH
• body can lower blood pH by moving H+ ions out of blood and into cells = use H+/K+ pump to move H+ into cell and move K+ out of cell and into extracellular space (blood / interstitium)
• so in order to help compensate for acidosis, end up with hyperkalemia
• only the case in certain acidosis, NOT respiratory acidosis, as CO2 is lipid soluble and is able to freely move from blood into cell without affecting potassium, and NOT metabolic acidosis of organics such as lactic acid or ketoacids

BETA-2 ADRENERGIC RECEPTORS

• stimulate Na+ / K+ pump - increase intracellular K+
• so Beta-Blockers do the opposite –> hyperkalemia

ALPHA-ADRENERGIC RECEPTORS

• cause potassium to shift out of cells and into blood via calcium dependent K+ channels
• so Alpha-agonists cause more hyperkalemia

HYPEROSMOLARITY
- hyperosmolarity in extracellular space causes water to shift out of cells –> excess potassium in cells –> potassium to shift out of cells –> hyperkalemia

CELL LYSIS
- so much potassium is kept in the cell that with cell lysis --> potassium released from cells --> hyperkalemia
⦁    severe burns
⦁    rhabdomyolysis
⦁    tumor lysis (chemo)

EXERCISE

• during exercise, excess ATP is used for energy
• the depletion of ATP triggers potassium channels to open = allows potassium to move down its gradient and out of the cell –> hyperkalemia
• usually the exercise shift is small, but if combined with beta blockers and/or kidney issues –> can lead to hyperkalemia

SYMPTOMS
- need normal K+ levels inside and outside the cell to maintain resting membrane potential to allow muscle cells to depolarize and contract

• if too much extracellular K+ levels = increases resting membrane potential and can cause contraction –> abdominal / intestinal cramping
• eventually the resting membrane potential gets so high that it’s above the threshold potential, once the muscle depolarizes and contracts, it can’t repolarize to allow for another muscle contraction -> weakness

⦁ abdominal / intestinal cramps - increased activity of smooth muscles in peritoneal cavity
⦁ muscle weakness - decreased intracellular K+ for skeletal muscle - ascending muscle paralysis / flaccid paralysis
⦁ diarrhea - increased activity of smooth muscle - peristalsis
⦁ heart arrhythmias / arrest - decreased cardiac myocyte conduction (tends to occur at K+ of 7-8)

DIAGNOSIS
⦁ labs: K > 5.5 mEq / L
- also check glucose, creatinine, cortisol

⦁ EKG

• peaked T waves - best seen in precordial leads (V1 - V6)
• shortened QT interval
• ST segment depression
• in severe cases = can also cause prolonged PR interval, absent P wave, and widened QRS complex

could be PSEUDOHYPERKALEMIA - lab error or
** MC due to Venipuncture **

TREATMENT
⦁ potassium-wasting diuretics (Loop + thiazide - Lasix)
⦁ calcium gluconate- to stabilize myocardial cell membrane = 1st line if severe symptoms, EKG changes or > 6.5/7 mEq/L
⦁ insulin + glucose - insulin shifts K+ into the cell. Glucose given to prevent hypoglycemia from insulin
⦁ sodium bicarb - not given unless metabolic acidosis also present
⦁ beta-2 adrenergic agonists
⦁ resins -binds K in GI tract for excretion (kayexalate = sodium polystyrene sulfonate)
⦁ severe cases = dialysis

Rapid acting therapies (calcium gluconate, insulin and glucose, β2-adrenergic agonists) are indicated in patients with ECG changes, or those with serum potassium greater than 7 meq/L.

Calcium gluconate is used in cases of hyperkalemia because it antagonizes the effect of potassium on the myocyte cell membrane

Calcium gluconate or chloride, followed by measures to reduce serum K+ levels, is the immediate treatment to stabilize cardiomyocytes and reduce the risk of arrythmias when hyperkalemia is present

ex: if patient on lisinopril and have hyperkalemia = likely developed hyperkalemia due to lisinopril, due to reduction in aldosterone

Question 2

HYPOKALEMIA

Answer 2

A decrease of 1 mEq/L in serum [K+] represents a total body K+ deficit of approximately 200-400 mEq. A further decrease of 1 mEq/L represents an additional deficit of 200-400 mEq.

Question 3

ACUTE PYELONEPHRITIS

Answer 3

pyelo = pelvis
nephro = kidney

pyelonephritis = inflammation of the renal pelvis of kidney

Renal pelvis = funnel-like structure of kidney that drains into the ureter

ACUTE PYELONEPHRITIS = inflammation of the kidney that develops quite quickly, usually due to bacterial infection

Pyelonephritis is defined as inflammation (usually due to infection) of the kidney with neutrophilic infiltrate in the interstitium.

UTI = infection of any portion of the urinary tract: upper = kidneys + ureter, lower = bladder + urethra

So Acute Pyelonephritis = type of Upper UTI

CAUSE OF PYELONEPHRITIS
⦁ *** MC cause = ascending bacterial infection
- initially starts as a lower UTI and then travels up ureter to kidney

RISK FACTORS (same as for lower UTI)
⦁ female sex
⦁ sexual intercourse
⦁ indwelling catheters
⦁ DM
⦁ urinary tract obstruction / urinary stasis
⦁ pregnancy: progesterone + estrogen cause ureter dilation –> inhibit bladder peristalsis

• ** VUR = Vesicoureteral Reflux = where urine is moving backwards up the urinary tract, from bladder back up ureters to kidneys
• due to failure of the Vesicoureteral Orifice = one-way valve at UVJ (between ureters and bladder) that prevents backflow

VUR = can be due to primary congenital defect or by bladder outflow obstruction, which increases pressure of the bladder and distorts the valve

Obstruction leads to Urinary Stasis - makes it easier for bacteria to adhere and colonize the urinary tract

MC BACTERIA INVOLVED IN UTI / PYELO
⦁    *** E. COLI ***
⦁    Proteus
⦁    Enterobacter
- all 3 commonly found in bowel flora

Xanthogranulomatous pyelonephritis is associated with Proteus sp. infection.

Hematogenous infection can also lead to pyelonephritis, but is much less common
- occurs due to septicemia or bacteremia, or infective endocarditis
⦁ Staph
⦁ E. coli

PATHOPHYSIOLOGY

• bacteria adhere to renal epithelium of tubules –> inflammatory response
• chemokines attract neutrophils to renal interstitium and affect mainly the cortex
• typically glomeruli and vessels of the kidney are spared (unlike in chronic pyelo / glomerulonephritis)
• as neutrophils infiltrate and die off, they are excreted in the urine –> WBCs in the urine
• Sometimes the neutrophils form a cluster in the tubule, or a CAST in the shape of the tubule => may therefore find WBC CASTS in the urine

SIGNS / SYMPTOMS
⦁    usually unilateral (affects only 1 kidney)
⦁    fever
⦁    chills
⦁    nausea / vomiting
⦁    tachycardia
⦁    flank pain / CVA tenderness

THESE SYSTEMIC SYMPTOMS HELP DIFFERENTIATE AN UPPER UTI FROM A LOWER UTI

Also may have symptoms of (similar to lower UTI)
⦁    dysuria
⦁    increased urgency / frequency
⦁    hematuria
⦁    suprapubic pain

DIAGNOSIS
o UA
⦁    WBCs in urine / pyuria = > 5 WBC / hpf, espec if > 10
⦁    + leukocyte esterase
⦁    + nitrites
⦁    WBC casts***
⦁    hematuria

cystitis is associated with WBCs in urine, but not WBC casts

o Urine Culture = ** definitive diagnosis **
⦁ > 100,000

o CBC: leukocytosis (elevated WBC count)
- normal WBC = 4,500 - 11,000

TREATMENT
o Antibiotics
⦁    1ST LINE = ** FLUOROQUINOLONES ** 
- cipro 500mg BID x 7 days
- levo 750mg BID x 5 days

⦁ PREGNANT = Rocephin / Ceftriaxone IV or IM + hospitalization

⦁ Ampicillin or Gentamicin

o stay well hydrated - fluid promotion will increase urine production, helping to flush bacteria out of urinary tract

o NSAIDS for pain

COMPLICATIONS
⦁ formation of renal abscess
⦁ chronic pyelonephritis
⦁ papillary necrosis - death of renal papilla tissue

• WBC casts = acute pyelonephritis
• RBC casts = nephritic syndrome: post-streptococcal glomerulonephritis, IgA nephropathy, and rapidly progressive glomerulonephritis. They are also associated with malignant hypertension.
• eosinophilic casts = chronic pyelonephritis
• waxy casts = chronic renal failure, ESRD
• hyaline casts = can be normal
• granular casts = acute tubular necrosis (ATN)
• ATN is the most common cause of acute renal failure in hospitalized patients. ATN is an intrinsic renal failure that can be due to any of the following; persistent hypovolemia, shock, sepsis, severe hemolysis, rhabdomyolysis, amino glycosides, and amphotericin B

Question 4

CHRONIC PYELONPHRITIS

Answer 4

Chronic pyelonephritis is a renal disorder defined as interstitial fibrosis and atrophy of tubules.

MC CAUSE OF CHRONIC PYELONEPHRITIS IN ADULTS = ** chronic urinary tract obstruction **

A common histologic finding seen in chronic pyelonephritis is tubules containing eosinophilic casts (colloids) resembling thyroid tissue also known as thyroidization of kidney.

Question 5

ASYMPTOMATIC BACTERIURIA

Answer 5

asymptomatic bacteriuria (ABU) occurs in 2-7% of pregnancies

ABU is diagnosed in a patient who has a positive urine culture / positive for nitrites + leukocyte esterase, but lacks symptoms of a urinary tract infection (UTI), such as dysuria, urgency, frequency, or hesitancy.

Criteria for asymptomatic bacteriuria include urine culture showing a single bacterial species with >100,000 colonies from a voided urine specimen, or >100 colonies from a catheter specimen, or Group B Streptococcus bacteria at any count.

Pyelonephritis is the most common complication and occurs in 20-40% of cases of untreated bacteriuria.

It is important to remember that ABU is always treated during pregnancy because it is more likely to lead to cystitis and pyelonephritis in pregnant women.

This phenomenon is due to physiological changes that occur in the renal and urinary collecting system during pregnancy that promote urinary stasis (progesterone-induced decrease in urethral tone and motility).

This patient should be treated with a 10-day course of antibiotics.

Urine culture should be repeated one month after treatment.

Common first line antibiotics in pregnancy include nitrofurantoin, cephalexin, cefuroxime, ampicillin

Question 6

WILM’S TUMOR = NEPHROBLASTOMA

Answer 6

WILM’S TUMOR = NEPHROBLASTOMA = malignant kidney tumor that involves metanephric blastemal cells (cells involved in kidney development)

** MC MALIGNANT KIDNEY TUMOR IN CHILDREN **

MC diagnosed by age 5, MC seen in kids age 2-3

MC abdominal malignancy in children

MC UNILATERAL

MC occurs in left kidney, but can occur in right kidney / both kidneys

• rare in adults

** MAY BE ASSOCIATED WITH ** other GU abnormalities
⦁ cryptorchidism (failure of 1 or both testes to descend)
⦁ hypospadias (urethra on underside of penis)
⦁ horseshoe kidney (kidneys fuse together)

** also associated with NEUROFIBROMATOSIS **

CAUSE
- mutations in the genes responsible for normal genitourinary development (kidneys + gonads)

Wilms Tumor 1 (WT1) = tumor suppressor gene
Mutations in the WT1 gene (such as deletion) seem to lead to the development of tumor cells seen with Wilm’s Tumor, on ** CHROMOSOME 11 **

WT1 mutations are sometimes part of a developmental syndrome that leads to other abnormalities as well as Wilm’s tumor - likely due to other mutations apart from WT1 gene mutation.

WAGR SYNDROME
⦁ Wilm’s Tumor (WT1 mutation)
⦁ Aniridia (absence of iris) (PAX6 mutation)
⦁ Genitourinary malformation (WT1 mutation) = (tumor or testes/ovaries, cryptorchidism, hypospadias)
⦁ Intellectual disability - mental Retardation (PAX6 mutation)

WAGR syndrome = Wilm’s tumor + Aniridia + Genitourinary malformations (cryptorchidism / hypospadias / tumor of testes or ovaries) + Retardation

DENYS-DRASH SYNDROME
⦁ Wilm’s Tumor
⦁ early onset Nephrotic Syndrome
⦁ Male Pseudohermaphroditism

BECKWITH-WIEDEMANN SYNDROME (WT2 gene)
⦁ Wilm’s Tumor
⦁ Macroglossia (large tongue)
⦁ Organomegaly
⦁ Hemihypertrophy (half body > other half)
(WIIIIDE = large tongue, large organs, large half body)

But Wilm’s Tumor, in majority of cases, occurs in otherwise healthy kids, and is not part of a syndrome
- Is usually not part of WT1 or WT2 mutations, or any developmental syndromes, therefore cause = unknown

Metanephric Blastemal Cells give rise to Stromal cells and Epithelial cells- all of which normally give rise to structures in the kidneys

Wilm’s Tumor is characterized by blastemal, stromal, and epithelial cells (triphasic tumor).

In Wilm’s Tumor mass = usually partly developed structures (glomeruli and tubules) = abortive structures

CLINICAL MANIFESTATIONS
⦁ flank or upper abdominal quadrant mass - large, palpable, unilateral, painless!
⦁ may have hematuria
⦁ Hypertension (due to renin secretion)
⦁ anemia (due to hematuria)
⦁ nausea / vomiting / anorexia
⦁ may have fever (may have been diagnosed with FUO initially)

Often noticed by parents when bathing or dressing child

• ** PAINLESS PALPABLE ABDOMINAL MASS = MC
• ** mass does NOT cross midline
• MC UNILATERAL ** - can be bilateral
• hypertension (tumor secretes renin)
• hematuria –> anemia
• may have abdominal pain, but usually PAINLESS
• nausea
• vomiting
• anorexia
• fever

Most likely site of metastasis of Wilms tumor is the
** LUNG **

EXAM = do NOT palpate abdomen if you suspect Wilm’s Tumor - could cause tumor to rupture, leading to spread of cancer cells to other parts of body (lung!)

DIAGNOSIS
⦁ ** abdominal ULTRASOUND ** = best initial test
⦁ CT with contrast or MRI = more accurate test

CXR to rule out Mets (lungs)

• Biopsy = contraindicated for diagnosis of Wilms tumor until complete / partial nephrectomy is done - can confirm wilm’s tumor then

TREATMENT

• depends on the extend of spreading
• overall prognosis = very good

⦁ Nephrectomy + Chemotherapy

The management of unilateral Wilms tumor is surgery followed by chemotherapy.

The management of bilateral Wilms tumor is chemotherapy followed by surgery.

Chemo can be used before kidney(s) removal to shrink size or after to destroy any remaining cancer cells

Can also do radiation after surgery - often used in children who had large sized wilm’s tumors or when tumor metastasized

Patient will present as → a 15-month-old male who is brought in to your office for his routine exam. On exam, you notice that he has no irises, consistent with aniridia. He is also found with a palpable, non-tender mass on the left side of his abdomen. On further questioning, his mother reveals that her cousin had a similar abdominal mass at a young age. An abdominal CT scan is obtained = WAGR SYNDROME!