RENAL DISEASES 2rename
zwinthrop's version from 2015-05-21 21:19
Renal Tubular Acidosis (RTA)
|Distal Renal Tubular Acidosis||TYPE: 1|
(1) Dec Luminal H+ ATPase number/activity → Hypokalemia. Causes = Sjogren’s (absent intercalated cell H+ ATPase pumps), Mutations in H+ ATPase pump subunit
(2) Inc Luminal Permeability → Hypokalemia. Causes = Ampho B (intercalates in distal nephron, punches holes)→ increase permeability; Less H+ secretion, lesa K+ reabsorbed.
(3) Dec Na+ Reabsorption in Principal Cells → Hyperkalemia. Principal cells indirectly influence intercalated cells H+ secretion.
PATHO: Defect in ability of α-intercalated cells to secrete H+ →no new HCO3 generated→ metabolic acidosis. Associated w/: hypokalemia, risk for Ca2+/PO4 kidney stones (due to inc urine pH/bone turnover). Nephrolithiasis: Hypercalciuria, Hypocitraturia. Acidemia → dec proximal reabsorption of filtered citrate→ hypocitraturia. Acidemia also → Ca2+ mobilization from bone → inc urinary Ca2+ excretion. High urine pH favors Ca x PO4 precipitation
CLINICAL: Urine pH > 5.5 ; Defect in α-intercalated cells; Hypokalemia; Kidney Stones (nephrolithiasis); Serum bicarb very low
TX: Bicarb (helps w/ K+ reabsorption); K+ citrate (prevents kidney stones).
|Proximal Renal Tubular Acidosis||TYPE: II|
RISKS/EPI: Multiple factors stop PCT from reabsorbing HCO3-: (1) Carbonic anhydrase Inhibitor , (2) Luminal Na-H exchanger, (3) Basolateral Na-K-ATPase, (4) Basolateral Na-HCO3 cotransporter.
ASSOC: Fanconi Syndrome; Glycogen Storage (Fabry’s); Carbonic Anhydrase Inhib; Multiple Myeloma; Amyloidosis
PATHO: Defect in PCT HCO3− reabsorption→ inc excretion of HCO3- in urine and subsequent metabolic acidosis. K+ wasting b/c increased HCO3- delivery to distal tubule (flow dependent mechanism
CLINICAL: Urine pH <5.5; Hypokalemia; Hypophosphatemic Rickets (take Ca2+ out of bones); Inc FE HCO3 – (>15%); Lower HCO3 absorption threshold (from 24--> 16).
|Distal Hyperkalemic Renal Tubular Acidosis||TYPE: IV|
RISKS/EPI: Decreased ALDO responsiveness: Diabetes (chronic Diabetic Nephropathy), Adrenal Insufficiency (dec Aldo), Congenital Tubulointerstitial Nephritis, K+ Sparing Diuretics (Spironolactone)
EPI: Causes: aldosterone production (e.g., diabetic hyporeninism, ACE inhibitors, ARBs, NSAIDs, heparin, cyclosporine, adrenal insufficiency) or aldosterone resistance (e.g., K+-sparing diuretics, nephropathy due to obstruction, TMP/SMX)
PATHO: Hypoaldosteronism→ hyperkalemia→ Dec NH3 synthesis in PCT→ Dec NH4+ excretion.
CLINICAL: pH < 5.5; Hypoaldosteronism; Hyperkalemia; DIABETICS.
|What is your Mneumonic?||HALV = Hyperaldosteronism, Antacid Use, Loop/Thiazide Diuretics, Vomiting.|
|What is contraction Alkalosis?||Generation: hypovolemia →↑HCO3- reabsorption; Decreased GFR → ↓ filtered HCO3- load; Hypovolemia/↓ GFR→ ↑RAAS→ ↑ renin → ↑ efferent resistance → ↑ filtration fraction → ↑ Peritubular osmotic pressure → ↑ proximal reabsorption of NaHCO3- (NaCl and H2O); ↑renin → ↑ AII and aldosterone → ↑ proximal Na+/H+ exchange → ↑ HCO3- reabsorption; ↑ distal Na+/K+ exchange →↓ intracellular K+ →↑ K+/H+ exchange → ↑ HCO3 reabsorption.|
Maintenance: Those mechanisms don’t turn off until stimuli for aldo and AII are turned off; Must fix effective circulating volume to down regulate aldo and AII→ then machinery goes back to normal, start reabsoribng bicarb.
|What is Persistent Hypokalemia?||Hypokalemia stimulates renal H+ secretion, and increases the H+/K+-ATPase in collecting duct → alkolosis/further K+ loss. Must fix low circulating K+ to turn off this metabolic alkalosis.|
|Describe the correlation between Cl- Depletion and Distal HCO3- Absorption||Can get Cl- depleted from: Posthypercapnic alkalosis, increased aldo, increased Na reabsorption, Hypokalemia. |
Cl- depletion →Increased H+ secretion via intercalated type A cells (H+ ATPase associated w/ passive cosecretion of Cl- w/ H+).
Cl- depletion→Reduced HCO3- secretion via intercalated Type B cells (Cl-/HCO3 exchanger in apical memrane, H+ ATPase in basolateral membrane).
|What is posthypercapnic Alkalosis?||After hypercapnia induced acidosis, body responds by secreting H+/Cl- →Cl- depletion→can lead to alkalosis. Must fix Cl- depletion to fix alkalosis.|
|What makes an alkalosis Cl-responsive or resistant?||Volume Depletion (Cl- responsive), Mineralocorticoid Excess (Cl- resistant).|
Responsive: GI losses (vomit), Renal Losses (Diuretics, post hypercapnia, recovery from lactic/ketoacidosis (overshoot), K+ def)
Resistant: Primary aldosteronism, Liddle/Bartter/Gitelman Syndromes, Cushing Syndrome, Renal Artery Stenosis, Chronic Kidney Disease, Adrenal Enzyme Defect, mineralocorticoid excess ( licorice, carbenoxolone, chewing tobacco).
Renal Tubular Defects
|Fanconi Syndrome||LOCATION: PCT|
PATHO: Secrete: AA, Gluc, HCO3-, PO4-
Result: Proximal RTA
Causes: Glycogen storage disease, Multiple Myeloma, Lead poisoning, Nephrotoxins.
|Bartter Syndrome||LOCATION: Thick Ascending LOH|
Autsomal Dominant defect in NKCC2
Result: Hypokalemia, Metabolic acidosis with Hypercalciuria
CLUE: Mimics chronic loop diuretic use.
|Gitelman Syndrome||LOCATION: DCT.|
PATHO: Auto recessive defect in NaCl in DCT
Result: Hypokalemia, Hypomagnesemia, Met Alkalosis, Hypocalciuria.
|Liddle Syndrome||LOCATION: Collecting Tubule|
Autosomal dominant gain of function in ENac
Result: HTN, hypokalemia, met alkalosis, hypoaldo
CLUE: Mimics chronic thiazide diuretic use
|Syndrome of Apparent Mineralocorticoid Excess||LOCATION: Collecting Tubule|
PATHO: Deficiency in 11B-hydroxysteroid dehydrogenase
Result: inc cortisol →inc mineralocorticoid receptor activity → HTN, hypokalemia, met alkalosis, hypoaldosterone
CLUE: Licorice (glycyrrhetic acid) can block activity of 11B-hydroxysteroid dehydrogenase
Lower Urinary Tract Patho
|Urge Incontinence||DEF: After urge to urinate, patient cannot get to bathroom in time to avoid leaking. Bladder pressure spikes due to uninhibited contractions:|
CAUSES: Bladder irritation (e.g. stone, infection, tumor); Cerebral cortex lesion; Spinal cord lesion above sacral cord level; Obstruction; Idiopathic.
OUTCOMES: Certain causes of urge incontinence (e.g. stone, infection, tumor, neurologic lesion) may harm the patient if not recognized and treated; If emptying is normal, no risk to kidneys; Skin breakdown, hygiene problems; Social isolation, decreased career options; Decreased exercise and activities.
|Stress Incontinence||DEF: Leaking urine during activities that increase intra-abdominal pressure (coughing, sneezing, jumping, lifting heavy objects)|
CAUSES: Most common: females→ childbirth (urethral mobility); males→ Prostatectomy; Scarring or fibrosis of urethra; Decreased estrogen in post-menopausal women; Pelvic radiation; Neurologic lesions at sacral cord level (impaired innervation to bladder neck or external sphincter).
OUTCOMES: Unlike urge incontinence, stress incontinence is almost never the initial presentation of a serious underlying pathology.If no other pathology, no risk to kidneys.
|Outline Normal Bladder Emptying||(1) Detrusor (bladder muscle) contracts--Innervation: Parasympathetic pelvic nerves→originate from spinal cord level S2-S4.Neurotransmitter is acetylcholine (muscarinic).|
(2) Proximal urethra opens (innervation controversial).
(3) External sphincter opens. Innervation: Pudendal nerve from S2-S4. Neurotransmitter is acetylcholine (nicotinic).
If all coordinated, no reflux backwards pressure and empty bladder
|Failure to Empty Bladder Symptoms||Types of Symptoms: Incontinence (“overflow incontinence”); Difficulty voiding; Urinary retention.|
|Outflow Incontinence Symptoms||Stress incontinence, Urge incontinence, or both types.|
|Failure to Empty Basic Mechanisms||A>>Weak or absent detrusor muscle contraction: (1) Neurogenic(2) Myogenic.|
(1) Neurologic lesions (innervation impaired)--Sacral spinal cord or cauda equina; Pelvic nerves going from sacral cord to bladder--Diabetes mellitus
(2) Myogenic (detrusor muscle too weak). Diabetes mellitus; Chronic overdistention (long term HTN); B>>Bladder outlet obstruction: (1)Functional ; (2) Anatomic.
(1) Functional→the sphincter does not open when the patient is trying to urinate. Pons coordinates voiding, so the external sphincter opens when the detrusor muscle contracts. Detrusor-sphincter dyssynergia: detrusor muscle contracts, but… sphincter also contracts, creating obstruction. Dyssynergia occurs when: sacral cord connection to bladder is intact and sacral cord connection to pons is disrupted.
(2) Anatomic →structure narrows the urethral lumen. Benign prostatic hyperplasia. Prostate cancer. Urethral stricture (almost always male patients). Urethral valves (male infants and boys). Large ureterocele (babies and children). Bladder stone or tumor. Anti-incontinence surgery (usually female patients).
|Outcomes of Failure to Empty||Bladder or kidney infections, Bladder or kidney stones, Hydronephrosis, Renal failure.|
|Detrusor-Sphincter Dyssynergia||DEF: Functional bladder outlet obstruction→ detrusor muscle contracts, but… sphincter also contracts, creating obstruction. Dyssynergia occurs when: sacral cord connection to bladder is intact and sacral cord connection to pons is disrupted. |
CAUSES: Spinal cord injury above level of sacral cord; Multiple sclerosis.
OUTCOMES: High-pressure voiding; Incomplete bladder emptying; Recurrent urinary tract infections; Hydronephrosis; Renal failure.