Week 7 (Exam 3) Flashcards
Pathogenesis of Primary Membranous Glomerulo-Nephropathy
In-situ immune complex formations involving Phospholipase A2 Receptor on Podocytes
Involves in MAC and IgG4
Usually presents as Nephrotic Syndrome
Acute Proliferative Glomerulonephritis presentation in children
Malaise, fever, nausea, oliguria and hematuria 1-2 weeks after recovery from sore throat
Dysmorphic red cells or abc casts, mild proteinuria, periorbital edema and mild-moderate HTN
Whats the etiological difference between Cystitis Cystic and Cystitis Glandulars (CC and CG)?
Utothelium metaplasia into buds (nests of von Brunn), then invades the lamina propria. In CC it then differentiates into cystic deposits. In GC, it differentiates into intestinal columnar mucin-secreting glands
Clinical presentation of Renal Cell Carcinoma
Classic Triad: Hematuria, Costovertebral pain, palpable flank mass
Clear cells are from Glycolgen and Lipid accumulation
Main Renal Loss mechanisms of hypokalemia
Diuretics Increased Mineralocorticoid (aldosterone, ENaC) Hypomagnesemia Increased Distal Delivery of Na and H2O RTA type 1 or 2 Intrinsic renal defect
Clinical presentation of WAGR
Genitourinary malformation: males have undescended testes and females have streak gonads or uterine malformations
Sx of Hypokalemia
Cardiac Arrhythmias Skeletal Muscle (esp Diaphragm) weakness Rhabdomyolysis Metabolic Alkalosis Nephrogenic Diabetes Insipidus
Pathophysiology of Gitelman Syndrome
AR mutations of NaCl co-Transporter (NCCT)
NaCl wasting, Hypovolemia, RAAS (increased collecting duct Na reabsorption, H and K secretion)
Increased Ca reabsorption
Hypomagnesemia from down regulating TRPM6 in DCT
Calcium and cardiac AP
Increased Ca raises the threshold (makes it harder)
Lowered Ca lowers the threshold (makes it easier)
glomerular pathology of chronic glomerulonephritis
normal, lipid in tubules
loss of foot processes, no deposits
Glomerular Pathology of Membranous Glomerulo-Nephropathy
Diffuse Capillary Wall Thickening without increased cells
Spikes of Silver Staining Matrix from BM to urinary space
Supepithelial deposits of dense IgG and G3 with overlying obliterated foot processes
How to replace a potassium deficit
Potassium Chloride: K increases by 0.1 for every 10 given
Most common benign renal neoplasia
Renal papillary adenoma (benign), less than 1cm
Rapidly Progressive Glomerulonephritis Type I
Anti-GBM Ab
Renal Limited, Goodpasture syndrome
Patterns of tubular damage in Toxic injury
Continuous necrosis in PCT and PST
Patchy necrosis in Ascending LOH
Criteria of Malignant HTN
180/120 BP
Papilledema, Retinal hemorrhages, encephalopathy, CV abnormalities, renal failure
Early sx are from increased intracranial pressure
Pathophysiology of Minimal change disease
Unknown, loss of glomerular polyanion, podocyte injury
Its a nephrotic syndrome
Proteinuria and effacement of glomerular foot processes without Ab deposits. Responds well to steroids
Prensents as Edema and FPF on Bx
Pathophysiology of Liddle Syndrome
Mutated ENaC channel in collecting duct
Prevents degradation of them from luminal surface of principle cells via ubiquitin (too many!)
Increases Na reabsorption and urine K and H hypokalemia and metabolic alkalosis)
Clinical manifestations of Liddle Syndrome
Resistant Hypertension
Hypokalemia
Metabolic Acidosis (saline non-responsive)
Glomerular Pathology of Post-infectious Glomerulonephritis
Endocapillary Proliferation, leukocyte infiltration
Granular IgG and C3 in GMB, maybe IgA
Supepithelial humps, sub endothelial deposits
Amiloride
Blocks luminal Na Channels in collecting duct
Spironolactone blocks aldosterone receptor in collecting duct
First line treatment for stage 2/moderate hyponatremia
Vaptan or Hypertonic NaCl
Clinical Applications of Spironolactone
counteracts K loss induced by other diuretics in the treatment of HTN
off-label for reducing fibrosis post-MI heart failure
Toxicities of HCTZ
Sulfonamide etc
Clinical manifestations of Chronic Kidney Disease
Starts silent, develops uremia
Persistently diminished GFR (below 60 3+ months)
Persistent albuminuria
Generally Irreversible
What happens with ethylene glycol damage to the kidney?
Virtually all PCT epithelial cells show swelling and vacuolization
Pathophysiology of IgA nephropathy
Unknown, recurrent hematuria or proteinuria
Isolated (or can be nephritic)
Clinical manifestations of AKI
Rapid decline in GFR
Severe can have oliguria or anuria
Maybe from Glomerular, interstitial, vascular, or ATN
Can be reversible or become CDK
Triamterene
Similar to amiloride for edema and off-label for HTN, rapidly absorbed, 6-9 hours, eliminated as drug metabolized
Criteria for End Stage Renal Disease
GFR blow 5% normal
End stage of uremia
Insulin and K
Drives K into the cell (decreases serum k)
Alkalemia, ICF donates H+ to the ECF
Benign Nephrosclerosis
Pattern of hyaline sclerosis of renal arterioles, small a
multi-focal ischemia of kidney parenchyma supplied by sclerotic vessels
Characterizations of Acute Proliferative Glomerulonephritis
Marked Hypercellularity
Leukocyte infiltration: exudative within glomerular tuft
Granular deposits of IgG, IgM, C3
Where do renal oncocytoma arise from?
Type A intercalated cells of cortical collecting ducts
(acid-base homeostasis)
Mahogany-brown and well-circumscribed with central stellate scar. Packed with Mitochondria
Goodpasture Ag
Peptide within noncollagenous regions of collagen IV
Acute pyelonephritis
Acute bacterial infection of the kidney 95% from the bladder with pre-existing defect Vesicoureteral Reflux (back-flow up ureter)
Pathophysiology of Postinfectious Glomerulonephritis
Immune complex mediated, circulating or planted Ag
Usually Nephritic Syndrome
Clinical Applications of Conivaptan
Treats euvolemic and hypervolemic hyponatremia
For Hospitalized, symptomatic pts unresponsive to fluid restriction
Watch out for too rapid of serum sodium correction
Cardiac Arrhythmias associated with Hypokalemia
Premature Atrial Contractions
Premature Ventricular Contractions
Tachycardia, Bradycardia, V Fib
Renal Angiomyolipoma
AD, Lesions of brain, skin, kidney, heart, lungs, eyes
Strong association with Tuberous Sclerosis/TSC
Chlorothiazide
Similar to HCTZ but poor oral absorption
Uremia
Azotemia + constellation of findings of renal damage
3 main reasons for hypokalemia
Transcellular Shift (Insulin, b2 agonist, m. alkalosis) Extrarenal Loss (GI: vomiting, diarrhea, Sweating) Renal Loss
Toxicities of Desmopressin
Black Box Hyponatremia
Differentiate Central vs Nephrogenic Diabetes Insipidus
Central: lack of ADH (tx with ADH agonist / dDAVP)
Nephrogenic: Unresponsive to ADH (tx with water and thiazide unless its from lithium: give amiloride instead)
Vaptan MOA
block ADH receptors at the collecting duct
Etiology of RTA 2
Most common in children is Cystinosis
Most common in adults with Fanconi is MM
Clinical applications of HCTZ
HTN, Not effective in patients with low GFR
Calcium nephrolithiasis
Negative Urine Anion Gap
Appropriate distal nephron urinary acidification
Symptoms of Uremia
CV: HTN, Atherosclerosis, Stenosis, CGF
GI: Occult bleeding, N/v, Uremic Fetor
Neuro: Uremic Encephalopathy, Amyloidosis
Skin: Fluid retention, CaP deposits, Nail Atrophy
Respiratory acidosis and K
Increaes serum K
RTA type 1 most common secondary causes
Auto-immune disorders
RTA type 2 most common secondary causes
Fanconi’s syndrome, MM, drugs
Medullary Sponge Kidney
Non-Hertiable, Benign
Medullary Cysts on Excretory Urography
Hematuria, UTI, Recurrent Renal Stones
3 groups of predisposing to Wilms Tumors patients
WAGR (wilms-aniridia-genital-retardation)
Denys-Drash Syndrome (gonadal and renal tumors)
Beckwith-Wiedemann syndrome (non-WT1, IGF 2)
Chronic Hypernatremia
Greater than 48 hours or unknown duration
Pathophysiology of Goodpasture
Anti-GBM COL4-A3 Ag
Rapidly Progressive Glomerulonephritis
Diagnosis of RTA 2
Urine pH can be high or low
Urine Anion gap is Negative
a-Intercalated cells transporters
H-ATPase
H/K-ATPase
Nephritic Syndrome
Glomerular Disease dominated by acute onset hematuria, proteinuria, HTN, Oliguria with Azotemia
Usually immune mediated glomerular injury
What bladder cancer staging is optimistic vs very bad?
Ta, Tis, T1 are low stage. Isn’t cured, but not deadly
T2 - T4, highly muscle invasive, is very bad
Visceral Epithelial Cell (podocyte) Injury
Abs causing foot process effacement (fusion).
Associated with Detachment of epithelial cells and protein leakage through defective GBM and filtration slits
Diagnosis of RTA 1
Unable to acidify urine pH below 5.5
Hypokalemia (urinary k wasting)
UAG is Positive
Advanced Renal Hyaline Arteriolosclerosis
Often found in diabetes
Thickened, tortuous afferent arteriole
Amorphous (thickened) vascular wall
Pathophysiology of Chronic Glomerulonephritis
Variable, usually presents as chronic renal failure
Metolazone
Long acting thiazide diuretic like HCTZ
Clinical manifestations of Gitelman Syndrome
Hypokalemia
Metabolic acidosis (non-saline responsive)
Low to normal blood pressure
HYPOCALCIURIA (opposite bartter), like w/ Thiazides
Hypomagnesemia
Normal Osmolality Gap
10
Where does urothelial carcinoma of the kidney originate
Urothelium of the Renal Pelvis
Presents with Hematuria, may block urinary outflow and lead to palpable hydronephrosis and flank pain
Clinical Applications of Conivaptan
Treats euvolemic and hypervolemic hyponatremia
For Hospitalized, symptomatic pts unresponsive to fluid restriction
Watch out for too rapid of serum sodium correction
Black box warnings of amiloride
hyperkalemia
Vaptan MOA
Prevents ADH-mediated insertion of the aquaporin water channels into luminal membrane of principal cells in collecting duct (prevents water reabsorption)
Rapidly Progressive Glomerulonephritis Type III
Pauci-Immune. NO anti-GBM Abs!
ANCA-Associated, Idiopathic
Granulomatosis with Polyangiitis, Microscopic Polyangiitis
Toxicities of Furosemide
Sulfonamide
Ototoxicity
Hyper-Glycemia, -uremia
Hypo-kalemia, -natremia, -calcemia, -magnesemia, etc
Papillary necrosis pattern of analgesic nephropathy
Red-brown necrotic papillae sloughed into calyces
Adult Polycystic Kidney Disease
AD PKD (polycystin) 1 / 2, always bilateral
Large multi cystic kidney, liver cysts, berry aneurysms
Hematuria, flank pain, UTI, renal stones, HTN
Where do sodium channel blockers work?
Cortical Collecting Duct
Glomerular Pathology of Goodpasture
Extracapillary Proliferation with crescents, necrosis
Linear IgG and C3, Fibrin in crescents
No Deposits, GBM disruptions, fibrin
How to Identify Acute Kidney Injury
Rapid Decline in GFR
Severe forms can have oliguria and Anuria
Maybe from glomerular, interstitial, vascular, tubular injury
Can be reversible or progress to CKD
Where do loop diuretics work?
Thin Ascending Loop
PKD 1 vs PKD 2
PKD1: 16p13.3, Polycstin-1, Cell-Cell/Cell-Matrix interaction
PKD2: 4q13-p23, Polycsytin-2, Ca2+ channel
RTA Type 4
Hyperkalemic RTA
Decreased Aldosterone Secretion or Aldosterone Resistance
Leads to decreased net H and K secretion in collecting duct
Crescentic Glomerulonephritis
Collapsed, compacted, glomerular tufts
Crescent shaped mass of proliferating visceral and parietal epithelial. Wrinkling of GBM, fragmenting and disruption
Rapid Obliteration of urinary space
Infiltrates of Macrophages and Leukocytes
Major pathological finding of Papillary urothelial neoplasms of low malignant potential
Thickened epithelium covering papillary projections
minimal cellular atypia
Exchange Resins
Sodium Polystyrene Sulfonate / Kayexalate (exchanges Na_ ions for K mostly in the colon) Zirconium Cycloslicate (exchanges Na and H ions for K throughout intestines) Patiromer (exchanges Ca+ for K primarily in colon)
How to treat Hyperkalemia via K removal
Loop Diuretics or Thiazide
Exchange Resins
Hemodialysis
Etiology of malacoplakia
Defective phagosome function and related to chronic infection (E coli, usually)
Where does Renal Cell Carcinoma arise from?
Renal Tubular Epithelium (adenocarcinoma)
Happens a lot with smoking
Multicystic renal dysplasia
non-heritable absence of ureter, cauasing obstruction
Irregular kidneys with cysts of various size
Bilateral= renal failure, surgically cured if unilateral
Rapidly Progressive Glomerulonephritis
Nephritic syndrome with rapid decline in GFR
Implies Glomerular Injury
Chlorthalidone
Similar to HCTZ but half life of 40-60 hours
Prolonged/stable response with proven benefits
Why are urinary diverticulae commonly acquired?
Persistent urethral obstruction (like prostatic enlargement)
1 neoplastic SIADH cause
Oat cell carcinoma
Classic phases of AKI/ARF
Initiation: 36 hours, oliguria
Maintenance: HyperKalemia
Recovery: HypoKalemia from urine loss, infection
Loop Diuretics MOA
Blocks NaK2Cl cotransporter in TAL
Glomerular pathology of chronic glomerulonephritis
Hyalinized glomeruli, replacement of virtually all
Granular or negative on fluorescence microscopy
Glomerular pathology of Dense-Deposit Disease aka MPGN II
Mesangial proliferative or membranoproliferazive patterns of proliferation, GBM thickening, splitting
C3, no C1q or C4
Dense deposits
Bartter Syndrome Type 3 Mutation
All are AR
CLC-Kb
Most common tumor of men
Testicular Germ Cell Tumors
IV K replacement
K Chloride, K Acetate (usually just for severe)
10 - 20 mEq/hour
Simple (renal) cysts
Non-heritable, benign
Single or several cysts, normal-sized kidneys
Microscopic hematuria
Clear cell carcinoma
Most common renal cell carcinoma
Non-papillary, sporadic 95%
When familial, chromosome 3 short arm deletions/translocations (VHL ts gene)
Treatment of Liddle Syndrome
Amiloride or Triamterene (blocks sodium channel)
Low salt diet
Clinical Manifestations of Bartter syndrome
Hypokalemia
Metabolic Alkalosis (saline non-responsive)
Low to normal BP
Hypercalciuria and Nephrocalcinosis
RTA Type 2
Proximal RTA
Decreased HCO3- reabsorption in PCT. Lost in urine, low in serum. Eventually stabilizes
K Homeostasis cells in the distal nephron
Principle cells for secretion
a-intercalated cells for reabsorption
Basement membrane is moth-eaten, or frayed
Alport Syndrome
Vaptan MOA
Prevents ADH-mediated insertion of the aquaporin water channels into luminal membrane of principal cells in collecting duct (prevents water reabsorption)
Primary vs Secondary Nephrotic Syndrome
Primary: Renal Only, primary kidney disease is most common in children
Secondary: Systemic, more common in adults (DM, SLE)
Amiloride
Blocks luminal Na Channels in collecting duct (ENaC)
Spironolactone blocks aldosterone receptor in collecting duct
Normal HCO3-
24
Adult-onset Nephronophthisis
AD
Corticomedullary cysts, shrunken kidneys
Salt wasting, polyuria
Tolvaptan
Selective AVP V2 receptor antagonist administered Orally
Hotta use it less than 30 days for hyponatremia (hepatotoxic)
It can also slow progression of adult PKD
Osmotic Demyelination Syndrome
Happens in Pontine and Extrapontine Neurons
Delayed 2 - 6 days
Can develop Locked in syndrome
Three major causes of decreased renal K secretion Hyperkalemia
Low Aldosterone Secretion Aldosterone Resistance (K sparing Diuretics) AKI or CKD (low GFR)
Best method for assessing renal K+ excretion
24 hour urine potassium
Licorice
Has glycyrrhizic acid, potentiates aldosterone effects in kidney and dose-dependently increases systolic BP
Bartter Syndrome Type 4 Mutation
All are AR
Barttin Mutation
3 circulating Auto-Abs in DMI
Anti-Insulin, -GAD, -ICA512
Xanthogranulomatous Pyelonephritis association
Proteus sp.
What would you order to assess the volume status of a hypotonic hyponatremic patient?
Random Urine Sodium Level
Urine Osmolarity
(serum Uric Acid if considering SIADH: high in urine)
Thiazide MOA
Block NaCl cotransporter in DCT
Mg is reabsorbed in primarily in TALH/distal nephron
Immune complexes in Subepithelial Humps
Acute Glomerulonephritis
How to treat Transcellular Shift Hyperkalemia
Insulin and Dextrose
B2 Agonist (albuterol)
Bicarb (likely not effective)
Risk of too rapid of sodium correction in chronic hyponatremia case
Osmotic Demyelination Syndrome (ODS) from brain swelling and rapid shrinking
Actue vs Chronic Hyponatremia criteria
Acute: Less than 48 hours
Chronic: Longer than 48 hours or unknown
Beckwith Widemann Syndrome clinical presentation
Hemihypertrophy, macroglossia
Major pathogenesis of Transcellular Shift Hyperkalemia
Pseudohyperkalemia Metabolic Acidosis Insulin deficiency, hyperglycemia, hyperolsmolarity Increased Tissue Catabolism Meds, Exercise, Blood Transfusion
Microscopy findings in Diffulse Proliferative Lupus Nephritis
Glomerulus really biggened, looks stuffed into Bowmans
Resultant decrease in urinary space
Anion Gap above 20
Suspect Alcohol ingestion
Sarcoma botryoides
Embryonal Rhabdomyosarcoma, Cambium layer of tumor cells right below the epithelium results in nevoid appearance
Most common malignancy associated with ectopic ADH production
Small Cell Lung Cancer
Focal Segmental Glomerulosclerosis Collapsing Variant
in HIV and mores in Black patients
Where do thiazide diuretics work?
DCT
Pediatric Polycystic Kidney Disease
AR
Enlarged, cystic kidneys at birth
Hepatic Fibrosis
Hereditary Segmental Glomerulosclerosis
Mutations in cell adhesion coding genes NPHS1 and 2
Those coding for Nephrin, Podocin, a-actinin 4 (AD)
TRPC6 (transient receptor potential calcium channel 6)
APOL-1 on Chr 22 in Black patients (related to resistance to trypanosomal infection)
Ethacrynic acid
Non-sulfonamide loop diuretic reserved for those with sulfa allergy
Bence-Jones proteins and the kidney
Causes or is indicative of a tubulointerstitial nephritis
Thin basement membrane lesion
Benign clinical course, like Alport syndrome involves mutations in genes coding for GBM type IV collagen
In spectrum of diseases that includes hereditary nephritis
Asymptomatic Hematuria, most are heterozygous
Eplerenone
More selective aldosterone antagonist than spironolactone
Approved for post-MI heart failure and alone for HTN
Toxicities of Desmopressin
Black Box Hyponatremia
Most common causes of End Stage Renal Disease
DM (primarily glomerular)
HTN (primarily vascular / arteriolar / tubulointerstitial)
Ddx of NAGMA
DURHAAM: DIARRHEA Ureteral Diversion RENAL TUBULAR ACIDOSIS Hyperalimentation Acetazolamide Addison's disease Misc
Mutations of invasive and bad bladder cancer vs superficial and non-invasive
TP53 (chr 17p) and RB is invasive
Chr 9 monosomy or deletions are usually fine
Oral K
K chloride, K phosphate, K bicarb (precursors citrate, gluconate)
Common Etiologies of RTA 1
Glue Sniffing and Sjogrens
Can manifest with nephrolithiasis or nephrocalcinosis
Malignant arteriolosclerosis
Injury associated with malignant / accelerated HTN
Ischemic kidneys, elevated renin
“flea-Bitten” appearance of renal hemorrhages
Polar Scarring of the kidney
Often from VUR with Chronic Pyelonephritis
Painless Hematuria
Think Urothelial (transitional cell) Carcinoma! Theres usually multiple tumors at initial diagnosis
glomerular pathology of focal segmental glomerulosclerosis
focal and segmental sclerosis and hyalinosis
“increasingly, a category of disease”
Mesangial Immune Deposits
IgA nephropathy
Normal Anion Gap
12
How would you identify a tubulointerstitial nephritis?
Inability to concentrate urine: polyuria (acute or chronic)
Metabolic alkalosis and K
Decreases serum K
Diagnosis and treatment of Pyroglutamic (5-oxoproline) acidosis
Urinary Organic Acid Screen
Tx: discontinue acetaminophen, IVF, N-Acetylcysteine
Eosiniphilic Cystitis
Infiltration of submucosal eosinophils, can also represent nonspecific subacute inflammation etc
Pathophysiology of focal segmental glomeruloscerosis
Primary: Podocyte injury by unknown mechanisms
Secondary: ex. by prior glomerulonephtriytis, HTN, HIV…
Usually presents as nephrotic syndrome
Most common causes of Hypokalemic Transcelluar Shift
Insulin
b2 Agonist
Metabolic Alkalosis
Nephritic vs nephrotic presentations
Nephritic has greater hematuria
Nephrotic has greater Proteinuria
Etiology of RTA 4
Deficiency of circulating Aldosterone (DM, drugs)
Aldosterone Resistance in collecting ducts
Both cause impaired Na reabsorption by principle cells
Hyperkalemia
Worsens Acidosis by preventing ammoniagenesis
Clinical applications for desmopressin
Central Diabetes Insipidus
Primary Nocturnal Enuresis
Glomerular pathology of IgA nephropathy
Focal mesangial proliferative glomerulonephritis, mesangial widening
IgA +/- IgG, IgM, and C3 in mesangium
Mesangial and paramesangial dense deposits
Bartter Syndrome Type 2 Mutation
All are AR
ROMK
How to treat Hyperkalemia with Peaked T waves
Calcium glutinate (stabilizes cardiac membrane)
Microscopy of malacoplakia
Foamy macrophages, multinuclear giant cells, some granulomas
Laminated mineralized concretions, Michaelis-Gutmann bodies, in the macrophages
Licorice
Has glycyrrhizic acid, potentiates aldosterone effects in kidney and dose-dependently increases systolic BP
Patterns of tubular damage in Ischemic injury
Patchy necrosis of PCT, PST, Ascending LOH
Nephrotic Syndrome (there’s 5 of them)
Glomerular Disease w/ severe proteinuria, hypoalbuminemia, edema, hyperlipidemia
Includes Membranous Nephropathy + Minimal Change Disease + Focal Segmental Glomerulosclerosis + Membranoproliferative Glomerulonephritis + Dense Deposit Disease (MPGN II)
Basically Leaky GBM (esp to albumin), RBCs don’t enter urine
Clinical presentation of malacoplakia
Bladder inflammation with 3-4 cm soft yellow, plaques
K sparing diuretics
Na channel blockers (triamterene, amiloride) Aldosterone Antagonists (spironolactone)
Metabolic Alkalosis ddx
Hypokalemia Vomiting or NG tube Diuretics Volume Depletion Mineralocorticoid Excess
Normal Arterial pH
Normal: 7.35 - 7.45
Prominent U wave
Hypokalemia
PAS Type IV Collagen Stain findings in Diabetic Glomerulosclerosis
Diffuse Capillary Basement Membrane Thickening
Diffuse Mesangial matrix increase
Acellular PAS+ nodules
Barium Toxicity
Blocks K+ channel and prevents efflux from cells
Causes hypokalemia
5% albumin
Expands the plasma volume compartment
Labs of Azotemia
Elevated BUN, Decreased GFR
Sx of GC and CC
Chronic irritation, frequency, dysuria, urgency, hematuria
Anatomical sites of kidney stone lodging
UPJ and UVJ (not thought to be at the ureteral crossing of the iliac vessels as much)
Subendothelial Immune Deposits
Lupus Nephritis
Membranoproliferative Glomerulonephritis
Bartter Syndrome Type 1 Mutation
All are AR
NKCC2
Hypokalemia Criteria
Serum K below 3.5
Histology of Papillary Renal Cell Carcinoma
Papillae and foamy macrophages in stalk
How does metabolic acidosis work in hyperkalemia
K enters the cells so H exits them
Decreased ammoniagenesis and ammonium chloride excretion in the kidneys
Acute Hypernatremia
Less than 48 hours
RTA Type 1
Distal RTA: unable to acidify urine
Decreased net H+ ion secretion in DCT, collecting duct
Glomerular pathology of Membranoproliferazive glomerulonephritis Type 1
Mesangial proliferative or membranoproliferazive patterns of proliferation, GBM thickening, splitting
IgG++ C3, C1q++ C4
Subendothelial Deposits
Loop Diuretics MOA
Blocks NaK2Cl cotransporter in TAL
Clinical presentation of interstitial cystitis (Hunner ulcer)
Chronic, persistent, painful, 30-40 yo women
Intermittent suprapubic pain, urinar frequency, urgency, hematuria, dysuria, Culture Negative
Most common defect associated with acute pyelonephritis
Defective Vesicoureteral Junction (children with UTIs)
Bladder Outlet Obstruction (prostatic hypertrophy)
3% and 5% NaCl
Expands the ECF while shrinking the ICF
ADAMTS13
Protease regulating vWF
Mutations founding TTP (prominent neuro sx)
Acute Post-Infectious Glomerulonephritis
Nephritic syndrome
Usually after Strep infection in children and young adults
Deposition of immune complexes, mainly sub epithelial
Neutrophils and glomerular cell proliferation. Good Px
Criterion for Hypernatremia
Serum Sodium above 145
Acute proliferative glomerulonephritis
Immune complex injury from exogenous Ag
Presents in adults with edema, elevated BUN, etc
Historical antecedent infection by b-hemolytic strep-specific nephritogenic strains of Lancefield Group A
Pathophysiology of membranoproliferazive glomerulonephritis (MPGN) type 1
Nephrotic when primary, nephritic when secondary
Immune complex mediated
What is usually the cause of bacterial urethritis
Gonorrhea, Chlamydia, HPV
Cardiac changes in hyperkalemia
V Fib
Bradycardia form AV block
Asystole
Bumetanide
Sulfonamide like furosemide but more predictable oral absorption
Spironolactone MOA
Competitive antagonist aldosterone receptors
Partial agonist at androgen receptors
K+ sparing diuretic
K losing diuretics
Thiazides (NaCl cotransporter blockers)
Loop Diuretics (Na K 2Cl Cotransporter blockers)
Carbonic Anhydrase inhibitors
Osmotic diuretics (nonreabsorbable solutes)
Why does Metabolic Alkalosis happen with Hypokalemia
K moves from inside to outside cell to maintain [K+]
Leads to H+ going inside from outside cell for electric reasons
Presentation of Alport Syndrome
Hematuria progressing to chronic renal failure
Nerve deafness and eye disorder (cataracts, etc)
X-Linked 85% of the time
Papillary necrosis pattern of DM
Pale Grayish necrosis
Limited to papillae
Alport Syndrome
Form of Hereditary Nephritis (homozygous)
Mutated genes encoding GBM type IV collagen
Manifests as Hematuria and slow progressing proteinuria and declining renal function
Glomeruli are normal until late in disease course
HAGMA ddx
GOLD MARK
Glycols, Oxoproline (acetaminophen), L- and D- Lactic Acidosis, Methanol, Aspirin, Renal Failure, Ketoacidosis
Renal Tubular Defects that can lead to RTA
Impaired H ion Secretion
Impaired HCO3- Reabsorption
HCTZ MOA
Blockade of NaCl cotransporter
K-Losing
Pathophysiology of Heymann Glomerulonephritis
Immune complex deposition on foot processes
Rapidly progressive Glomerulonephritis Type II
Immune Complex
Idiopathic, Post-Infectious Glomerulonephritis
Lupus nephritis, Henoch-Schonlein, IgA Nephropathy
Clinical presentation of Denys Drash
Gonadal Tumors
Pathophysiology of Bartter Syndrome
Transporter mutations at Thick Ascending Loop
NaCl loss, volume depletion, 2nd hyperaldosteronism
Cl- loss in macula dense causes PGE2 increase: renin (more aldosterone, hypokalemia, met alkalosis)
“Net result is like Loop Diuretics”
Frequent misdiagnosis of Polypoid cystitis
Papillary carcinoma. Look for this in in-dwelling catheters as this irritates the bladder mucosa
Diagnostics of Liddle Syndrome
Genetic testing, Low Aldosterone levels and renin levels
Two eponymic diseases associated with IgA Nephropathy
Berger Disease (renal, not systemic) Henoch-Schönlein Purpura
Normal PCO2
40
Acquired Renal Cystic Disease
Non-heritable, dialysis-dependent
Cystic degeneration in end-stage kidney disease
Hemorrhage, erythrocytosis, neoplasia
Clinical applications of Furosemide
Management of edema
Decreases preload, EC volume, Rapid dyspnea
Treatment of HTN (works with low GFR, unlike thiazides)
Where is NH4 produced?
From Glutamine metabolism in PCT
Ddx of increased Serum Osmolality Gap
Methanol Ethanol Diethylene glycol (diuretic mannitol) Isopropyl alcohol (rubbing alcohol) Ethylene Glycol
Insulin and K
Drives K into the cell
Alkalemia, ICF donates H+ to the ECF
Principle Cell Transporters
Na channel: creates net luminal negative charge
Indirectly favors tubular H secretion
Wire loops on light microscopy
Renal Glomerular capillary basement membrane with sub endothelial dense deposits (also in mesangium)
Found in SLE
Metabolic acidosis and K
Increases serum K
0.45% NaCl
Expands ICF and ECF, but mostly the ECF
Hyperkalemia criteria
Serum K over 5.0 or 5.5
Pathophysiology of Dense Deposit Disease (MPGN type II)
Auto-Ab, alternative complement pathway via C3NeF (nephritic factor) binding C3 convertase
“unique permeation of glomerular basement membranes by electron dense material”
Usually presents as Hematuria and chronic renal failure
RTA type 2 most common secondary causes
Fanconi’s syndrome, MM, drugs
Histology of Interstitial cystitis (Hunner ulcer)
Mast cells, lymphocytes
Inflammation and fibrosis of the bladder wall, fissures
Oral K
K chloride, K phosphate, K bicarb (precursors citrate, gluconate)
Three sources of Pseudohyperkalemia
Transcellular shift:
RBC hemolysis (during venipuncture)
Serum Blood samples (clotted blood samples)
Leukocytosis
K losing diuretics
Thiazides (NaCl cotransporter blockers)
Loop Diuretics (Na K 2Cl Cotransporter blockers)
Carbonic Anhydrase inhibitors
Osmotic diuretics (nonreabsorbable solutes)
Emergency management of hyperkalemia
IV calcium (antagonize cardiac effects) Redistribute K into cells (insulin, glucose, bicarb, b2) K elimination (K-losing diuretic, mineralocorticoid, etc) Monitor Intake
Sickle Cell Nephropathy
generally hematuria and hyposthenuria
Patchy papillary necrosis
Sometimes proteinuria, rarely nephrotic
Post-renal azotemia
Seen when urine flow is obstructed distal to calyces and renal pelvis
Eplerenone
More selective aldosterone antagonist than spironolactone
Approved for post-MI heart failure and alone for HTN
Familial Juvenile Nephronophthisis
AR MCKD1 and 2 mutations
Corticomedullary Cysts, Shrunken Kidney
Salt Wasting, Polyuria, Polydipsia, Growth Retardation
Epimembranous Immune Deposits
Membranous Nephropathy
Heymann Glomerulonephritis
Osmotic pressure of glucose (or any non-dissociating solute) at 1mmol/L
19.3 mmHg
Positive Urine Anion Gap
Inappropriate Distal Nephron Urinary Acidification
Differentiate Central vs Nephrogenic Diabetes Insipidus
Central: lack of ADH (tx with ADH agonist / dDAVP)
Nephrogenic: Unresponsive to ADH (tx with water and thiazide unless its from lithium: give amiloride instead)
Wilms tumor Histopathology
Often have precursor Nephrogenic Rests
triphasic (favorable): Blastemal, epithelial, stroll
anaplastic (unfavorable): Diffuse (always bad) or Focal
Follicular Cystitis
Aggregation of lymphocytes in lymphoid follicles in the mucosa and underlying wall. Usually associated with Chronic Infection
Triamterene
Similar to amiloride for edema and off-label for HTN, rapidly absorbed, 6-9 hours, eliminated as drug metabolites
Pre-renal azotemia
From Hypoperfusion of the kidneys in the absence of primary renal parenchymal damage
Ex. Hemorrhage, shock, CHF, volume depletion
Thiazide MOA
Block NaCl cotransporter in DCT
Mg is reabsorbed in primarily in TALH/distal nephron
Delta Delta Gap
Used in patients with HAGMA to determine if there is a coexistent NAGMA or Metabolic Alkalosis
Typical vs Atypical HUS
Typical: from E Coli O157:H7 or Shigella
Atypical: Inherited complement mut, endothelial injury (chemo / immunosuppression), other
Black box warnings of amiloride
hyperkalemia
