Renal Flashcards
[Renal anatomy and embryology]
- Describe potter syndrome, causes, and the clinical signs
- Describe Horseshoe kidney
- Biggest concern for OBs during surgery
1A. Potter sequence: oligohydramnios (too little amniotic fluid) --> compresses fetus --> limb deformities and flat face, chest compression --> pulmonary hypoplasia --> death B. caused by ARPKD, bilateral renal agenesis (urine contributes to amniotic fluid), posterior urethral valves C. POTTER syndrome Pulmonary hypoplasia Oligohydramnios Twisted face Twisted skin Extremity defects Renal failure
- Horseshoe kidney - kidneys fuse and trapped under inferior mesenteric artery
- function normally but increased risk for obstruction, renal stones, hydronephrosis (swelling due to build up of urine and obstruction to urine outflow)
- associated with Turner (XO), Trisomy 13, 18, 21 - accidentally ligating the ureter, since the ovarian vessels (uterine artery; vas deferens in men) are anterior to the ureter
“water under the bridge”
[Renal physiology] Differences between renal tubular acidosis 1. Type 1 2. Type 4 3. Type 2
RTA - disorder of tubules –> normal AG metabolic acidosis
- Type 1 - defect in ability of alpha intercalated cells in collecting duct to secrete H+ –> metabolic acidosis
- urine pH > 5.5 bc cells cannot acidify
- hypokalemia bc cells cannot reclaim K+, ↑ risk for CaP04 kidney stones due to ↑ urine pH
- causes - amphotericin B antifungal and analgesic toxicity, obstruction (kidney stone, congenital) - Type 4 - hypoaldosteronism –> hyperkalemia –> ↓ NH3 synthesis in PCT –> ↓ NH4+ excretion –> ↓ HC03- regeneration
- urine pH <5.5 bc lack of ammonia NH4+ as a buffer
- causes - ↓ aldosterone production –> RAS system (ACEI, ARB), impaired aldosterone metabolism (heparin, ketoconazole), diabetic hyporeninism, cyclosporine, adrenal insufficiency
- aldosterone resistance (eg K+ sparing diuretics - amiloride, triamterene, eplerenone, spironolactone) - Type 2 - defect in PCT HC03- reabsorption –> serum HC03- drops –> metabolic acidosis
- urine pH < 5.5
- associated with hypophosphatemia and hypokalemia
- causes - Fanconi syndrome and carbonic anhydrase inhibitors, acetazolamide (Diamox diuretic)
[Renal physiology] Describe how the following are processed and the parameters they approximate: 1. Glucose 2. Inulin 3. p-aminohippurate (PAH)
Clearance = (Urine flow rate * urine concentration) / plasma concentration
- Glucose and AA - filtered out then 100% reabsorbed
- Inulin - filtered, neither reabsorbed nor secreted
- approximates glomerular filtration rate (GFR), also approximated by creatinine (muscle breakdown product; little less accurate bc a little is secreted)
- clearance = GFR for inulin, creatinine
- normal GFR = 100 mL/min - p-aminohippurate (PAH) - filtered, then completely secreted
- approximates renal plasma flow (RPF)
- clearance > GFR –> net tubular secretion of PAH
FF = GFR/RPF
[Secondary HTN]
1. Describe mechanisms of blood pressure up-regulation
- Describe renal causes of secondary HTN
A. Renal disease
B. Renovascular
1A. Kidneys - blunted pressure natriuresis –> renal salt volume retention
B. RAAS activation
C. SNS - alpha1 receptors –> vasoconstriction
- beta1 receptors on JGA cells –> ↑ cardiac contractility/HR, increased renin secretion
D. vascular wall remodeling (chronic, irreversible) - onion skinning appearance
2A. Renal disease - usually bilateral eg diabetic nephropathy, polycystic kidney disease
- pathogenesis: kidneys not working properly –> Na/fluid retention – increased CO and BP –> increased perfusion to kidney –> decreased renin release
B. Renovascular - can hear bruits
- microvascular eg vasculitis
- renal artery stenosis due to atherosclerosis (older pop), fibromuscular dysplasia (younger pop), trauma
- unilateral (renin dependent)
- bilateral (not renin dependent)
[Secondary HTN]
1. Differentiate what happens with bilateral vs unilateral kidney stenosis
1 Bilateral (one kidney, one clip) - decreased perfusion –> RAS –> BP increases, Na+ increases –> become edematous as circulating volume increases
- high blood volume
- renin activity normal, decreases as you retain fluid volume
- Unilateral (two kidney, one clip)- decreased perfusion –> RAS –> BP increases
- Na+ decreases because good kidney is hyperperfused (due to renin-induced HTN) –> diureses –> net effect is loss of fluid and salt in the body
- decreased blood/plasma volume
- renin activity high
[Secondary HTN]
Describe adrenal cortex causes of secondary HTN incl cause, diagnosis, and clinical signs/tx
A. Cushings
B. Primary hyperaldosteronism
- Cushings
A. Causes - pituitary adenoma (makes ACTH), ectopic ACTH, adrenal hyperplasia (makes cortisol)
B. Diagnosis - high 24 hr urine free cortisol, ACTH levels
C. Clinical signs - excess glucocorticoid (cortisol) levels –> activate mineralocorticoid receptors –> ↑ Na+ retention
–> ↑ BP, ↑ blood glucose, obesity, body habitus (moon facies, buffalo hump), abdominal stria, depression, immune deficiency - Primary hyperaldosteronism
A. Causes - bilateral adrenal hyperplasia (most common), unilateral adenoma, neoplasm, familial
B. Diagnosis - ↑ BP, hypokalemia and higher-normal Na
- low plasma renin activity PRA (bc of volume expansion)
- ↑ serum aldosterone SA; SA:PRA >25
C. Clinical signs
- aldosterone acts at DCT to ↑ Na+ reabsorption and K+ secretion
- low serum K –> inhibits ADH –> mild nephrogenic DI –> slight increase in serum Na+
D. Treatment - K+ sparing diuretic eg spironolactone, surgery
[Secondary HTN]
Describe causes of secondary HTN incl cause, diagnosis, and clinical signs/tx
1. Pheochromocytoma
2. Drug-induced
- Pheochromocytoma - rare
- neuroectodermal chromaffin cell tumor of the adrenal medulla
A. Causes - sporadic (90%), unilateral (90%), adrenal only (90%), benign (90%)
B. Diagnosis - plasma metanephrines (epi/norepi metabolites), 24hr urine catecholamine secretion
- localize via CT, MRI
C. Clinical signs - usually norepi secreting –> alpha adrenergic receptor activation –> intermittent diffuse vasoconstriction –> episodic HTN and sweating
- pallor, headache (90%), palpitations, postural hypotension - Drug-induced
- sympathomimetics (decongestants, bronchodilators, cocaine, meth)
- steroids (glucocorticoids, mineralocorticoids, estrogens, androgens)
- NSAIDs, EPO, heavy metals eg lead, thalium
[Secondary HTN]
Describe causes of secondary HTN incl cause, diagnosis, and clinical signs/tx
3. Pregnancy associated
4. Others
- Clinical clues of secondary HTN
- Pregnancy associated
- 3rd trimester –> increased BP and proteinuria –> HELLP
(HTN Elevated Liver function tests - Low Platelets)
- need to induce delivery immediately - Other causes - thyroid (hyper or hypo), hyperparathyroidism, coarctation of the aorta (Systolic murmur front and back, check leg BP)
- Clinical clues
A. Hx - new onset, young age, tx resistant, hx of renal disease or smoking
- family hx of renal/thyroid/adrenal
B. Physical - cushingoid habitus, tremor, thyromegaly
- PVD - abdominal/carotid bruits, poor peripheral pulses
- postural hypotension
C. Labs - serum creatinine, electrolytes, glucose, Ca2+, urinalysis
[Childhood Renal Disorders]
Describe normal nephrogenesis
Normal nephrogenesis - derived from intermediate mesoderm
Three stages:
i. pronephros - until week 4, then degenerates
ii. mesonephros - interim kidney until week 12, then contributes to male genitals
iii. metanephros - permanent, appears in week 5
- Metanephric kidney has ureteric bud and metanephric mesenchyme (interacts with ureteric bud to induce differentiation of nephron from glomerulus to DCT)
- Kidneys start low and rotate/ ascend into their position
- Vascularization by angiogenesis
- Nephrogenesis begins - complete by 35 weeks (~1M nephrons/kidney)
- renal pelvis/calyces (also ureter and collecting duct) form from ureteric bud
[Childhood Renal Disorders] Describe CAKUT (congenitalabnormalities of kidney and urinary tract) 1. Cystic dysplastic 2. Vesicoureteral reflux (VUR) 3. Cross fused ectopy
CAKUT - MCC of chronic kidney disease and ESRD (end stage renal disease)
- Cystic dysplastic - Ureteric bud fails to induce differentiation of metanephric mesenchyme –> nonfunctional kidney consisting of cysts and connective tissue (esp cartilage)
- noninherited, usually unilateral
- type of renal dysplasia (improper growth) - Vesicoureteral reflux (VUR) - backward flow of urine from the bladder into the kidneys due to valve defect
- most common urologic anomaly in children
- associated with short intravesicular ureter –> UTIs and hydronephrosis (dilation of renal calyces and pelvis due to obstruction of urine outflow) - Cross fused ectopy - due to abnormal renal ascent, kidneys can fuse, be on the same side, or have crossed ureters; usually asymptomatic, just have to monitor
[Childhood Renal Disorders]
Describe genetic disorders of the kidney incl cause, clinical signs
1. Autosomal recessive polycystic kidney disease (ARPKD)
2. Autosomal dominant polycystic kidney disease (ADPKD)
PKD - inherited, bilateral renal enlargement secondary to multiple cysts
- Autosomal recessive (ARPKD) - cysts in collecting ducts
A. Cause - AR mutations in PKHD1 gene (fibrocystin protein)
B. Clinical - presents in infants with HTN, renal liver and cardiac failure, and Potter sequence
- associated with congenital hepatic fibrosis and liver cysts –> portal HTN - Autosomal dominant (ADPKD) - cysts in tubules (PCT, LOH, DCT)
A. Cause - AD mutations in PKD1 (85%) or PKD2 (15%) which encode polycystin 1 and 2 (cilia proteins) on chromosome 16
B. Clinical - bilateral renal cysts develop over time, usually symptomatic in early adulthood (huge kidneys)
- HTN (due to increased renin)
- hematuria, bleeding into cysts –> infection or stones
- flank pain, acute and chronic pain, UTIs
- proteinuria
- associated with berry aneurysms (cause of death) and mitral valve prolapse
[Childhood Renal Disorders]
Describe genetic disorders of the kidney incl cause, clinical signs
3. Alport’s syndrome
4. Thin basement membrane syndrome
- Alport’s syndrome i.e. hereditary nephritis - basement membrane disorder
A. Cause - mutations in genes encoding alpha chain of type IV collagen proteins; X-Linked Dominant
- usually family hx of deafness and renal failure
B. Histology
LM - glomerulosclerosis
EM - thin BM with basket weave appearance
C. Clinical - “can’t pee, can’t see, can’t hear a bee”
- ocular abnormalities (anterior lenticonus)
- sensorineural hearing loss –> deafness
- BM thickened, frayed, split –> microscopic hematuria, progressive proteinuria
- ESRD by mid-30s
- start on ACEI (to decrease proteinuria and renal scarring) - Thin basement membrane syndrome i.e. familial benign microscopic hematuria
A. Cause - mutation in genes encoding alpha chain of type IV collagen proteins
B. Histology
EM - thin BM
C. Clinical - asymptomatic microscopic hematuria
- excellent prognosis - no renal failure, follow over time but no biopsy needed if no proteinuria
[Childhood Renal Disorders]
Describe acquired disorders of the kidney incl cause, clinical signs
1. Hemolytic Uremic syndrome (HUS)
2. Idiopathic nephrotic syndrome
- Hemolytic Uremic syndrome (HUS) - thrombotic microangiopathy
A. Cause - verotoxin –> vascular endothelium damage –> platelet microthrombi –> RBC shearing
i. Typical HUS - bloody diarrhea (+) - secondary to E. Coli 0157:H7 (undercooked meat), shigella, salmonella
ii. Atypical HUS - no diarrhea - secondary to strep pneumo
B. Clinical - endothelial cell swelling
i. fever
ii. microangiopathic hemolytic anemia - with schistocytes
iii. thrombocytopenia
iv. renal insufficiency *more HUS
v. CNS problems (e.g. seizures) *more TTP - Idiopathic nephrotic syndrome - losing protein in kidney
A. Cause - idiopathic; clinical diagnosis
B. Clinical - need all 4 things to be consistent
i. proteinuria
ii. edema
iii. hypoalbuminemia (<2.5)
iv. hyperlipidemia (>240)
- 2 types: minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS)
- steroids, low salt diet
[Acute Kidney Injury]
1. Define AKI
- Classes of AKI
A. Risk
B. Injury
C. Failure - Describe how the following vascular regulators affect GFR –>
RAS
- AKI, prev known as acute renal failure (ARF) - acute, severe decrease in renal function; can be reversible
- hallmark is azotemia (↑ in nitrogenous waste products in the blood) and oliguria (decreased urine production) - Classes
A. Risk - >1.5x SCr, ↓ urine output for >6hrs
B. Injury - >2x SCr, ↓ urine output for >12hrs
C. Failure - >3x SCr, ↓ urine output for >12hrs
- ↑ serum creatinine implies kidney damage has already occurred
* small increases when SCr is in lower range (1-4 mg/dL) –> big decreases in GFR/kidney function (because of the L shape of the curve) - RAS - releases renin in response to
- decrease in afferent arteriole pressure
- decrease in tubular flow rate
- decrease in Na+ or Cl- concentration at macula densa
- stimulation of beta1 adrenergic receptors in JG cells
- leads to AI –> AII –> binds to receptors on afferent and efferent arterioles (more on efferent) –> more vasoconstriction on efferent arteriole –> ↑ GFR
[Acute Kidney Injury]
Describe how the following vascular regulators affect GFR
1. Prostaglandins
- Autoregulation
A. Myogenic reflex
B. Tubuloglomerular feedback
- Prostaglandins
A. Vasodilators - PGE2, PGI2 –> dilate afferent arteriole –> ↑ GFR ↑ RPF, - FF
B. Vasoconstrictors - PGH, thromboxane
- vasoconstrictors (AII, endothelin, norepi) –> stimulate production of PGE2 and PGI2
- when vasoconstrictor levels increase (volume depletion, CHF, ascites, nephrotic syndrome) –> GFR becomes dependent on PGE2/PGEI2
- NSAIDs inhibit PGE2–> lose prostaglandin vasodilation –> cause AKI
- ACEIs inhibit AII (constricts efferent arteriole –> ↑GFR ↓RPF) –> contraindicated in renal artery stenosis - Autoregulation - ensure that kidneys can maintain GFR with normal changes in BP
A. Myogenic reflex - ↑ BP in lumen of arterioles –> stretches wall –> reflex constriction of smooth muscle cells in endothelium –> reduces blood flow and pressure requires intact endothelium
B. Tubuloglomerular feedback - ↑ glomerular capillary BP –> ↑ GFR –> ↑ tubular fluid flow rate –> ↑ NaCl delivery to macula densa (junction between TAL and DCT) –> macula densa cells release adenosine –> constriction of afferent arteriole –> reduces GFR towards normal
[Acute Kidney Injury]
1. Describe Prerenal azotemia
A. Causes
B. Lab results
- Describe postrenal azotemia
A. Causes
B. Lab results
- Prerenal azotemia - due to decreased blood flow to kidney –> poor perfusion –> ↓ GFR, azotemia, oliguria
* most common form of kidney failure seen in hospitalized patients
A. Causes:
- low ECV / volume depletion (hemorrhage, heart/liver failure, sepsis)
- renal artery stenosis/thrombosis
- drugs - secondary injuries to low volume (IV contrast - vasoconstrictor, indinavir - crystallizes)
B. Labs:
- serum BUN:creatinine >15 (indicates dehydration)
- urine osmolality > 500 mOsm/kg
- FENa < 1% (tubular function intact - kidneys reabsorbing Na+ bc patient is volume depleted)
*Creatinine and kidney function will improve within 24 hrs if you give fluids - Postrenal azotemia - obstruction of urinary tract downstream of kidney (eg ureter) –> decreased outflow –> ↓ GFR, azotemia, oliguria
A. Causes: tumors, kidney stones, BPH
*do ultrasound to rule out postrenal causes
B. Labs:
i. early stage - same as prerenal bc tubular pressure forces BUN reabsorption
ii. late stage –> tubular damage
- serum BUN:Cr < 15
- urine osm < 500 mOsm/kg
- FENa > 2%
[Acute Kidney Injury] List the following that would be in the DD for AKI - Renal (Intrinsic) 1. Acute tubular necrosis ATN A. Pathogenesis B. Causes C. Phases D. Findings
- Acute tubular necrosis most common cause of intrarenal AKI
A. Pathogenesis: injury and necrosis of tubular epithelial cells –> detach from basement membrane –> slough into lumen and block tubules –> obstruction decreases GFR
- pathologic diagnosis (need to do biopsy)
B. Causes
i. ischemic injury- ↓ blood supply due to sepsis, shock, hemorrhage, post-op
- PCT particularly susceptible to ischemia
- preceded by prerenal azotemia
ii. nephrotoxic injury - drugs (vancomycin, aminoglycosides eg streptomycin and gentamicin, lead, cisplatin, amphotericin antifungal), crush injury (myoglobinuria), hemoglobinuria (hemolysis)
- ethylene glycol, urate (tumor lysis), radiocontrast dye
C. 3 phases, reversible cause of AKI!
i. inciting event
ii. maintenance - low urine output (oliguria) for 2-3 weeks as tubular cells regenerate
iii. recovery - polyuria, might need supportive dialysis
D. Findings
i. clinical: granular “muddy brown” casts in urine (of dead epithelial cells); elevated BUN and Cr, hyperkalemia with metabolic acidosis
ii. lab: BUN:Cr <15, FENa > 2%, urine osm < 500, decreased GFR
[Acute Kidney Injury]
List the following that would be in the DD for AKI - Renal (Intrinsic)
2. Acute interstitial nephritis AIN A. Causes B. Histology C. Clinical signs D. 5 P's
- Acute interstitial nephritis AIN
A. Causes - Drug-induced allergic hypersensitivity reaction not dose dependent –> Drugs act as haptens and induce HSN
- less commonly, secondary to systemic infections (eg EBV, CMV, TB, mycoplasma) or autoimmune (SLE, Sjogrens, sarcoidosis)
B. Histology - acute interstitial inflammation - infiltrate forms circular band around vessel, more edema than infiltrate
- interstitial edema with infiltration of lymphocytes/macrophages, eosinophils
- glomeruli OK except for with NSAIDs
C. Clinical -
- allergic response –> fever, RASH, hematuria, CVA tenderness, oliguria
- acute rise in Cr temporally related to the drug or infection
- pyuria (pus/WBCs in urine, esp eosinophils)
- azotemia (↑ BUN, SCr), but minimal proteinuria
- urine sediment with WBC casts
D. 5 P's Pee (diuretics) Pain-free (NSAIDs) Pencillins (amoxicillin, ampicillin) and cephalosporins (ceftriaxone) PPIs (omeprazole) rifamPin
[Acute Kidney Injury]
List the following that would be in the DD for AKI - Renal (Intrinsic)
4. Renal papillary necrosis
5. Vascular
Indications for dialysis
4. Renal papillary necrosis A. Causes - SAAD Sickle cell Acute pyelonephritis Analgesic - NSAID - abuse (chronic) Diabetes mellitus B. Clinical - sloughing of necrotic renal papillae --> gross hematuria, proteinuria, and flank pain
- Vascular causes
A. Causes -
- ANCA associated small vessel vasculitis e.g. Wegener’s, Churg-Strauss
- TMA (thrombotic microangiopathy) i.e. TTP, HUS, DIC
B. Clinical - extra-renal findings eg fever, rash, diarrhea, hemoptysis –> systemic signs
Indications for Dialysis - AEIOU
Acidosis (pH <7.1)
Electrolyte abnormalities (hyperkalemia)
Ingestions i.e. SLIME –> Salicylates (aspirin), Lithium, Isopropanol, Methanol, Ethylene glycol (treat with ethanol or fomepizole)
Overload (fluid overload refractory to diuresis) eg CHF
Uremia (BUN>100 mg/dl)
[Chronic Kidney Disease] 1. Define the following measures of renal function + normal values A. GFR B. Clearance - inulin vs creatinine C. BUN
- Define CKD
1A. GFR (100 ml/min) - amount of plasma filtered across glomerular capillaries; index of function of kidneys
B. Clearance - estimate since GFR cannot be measured directly
i. inulin (125 ml/min) is gold standard
ii. creatinine (0.7-1.2 mg/dL) is used but less reliable (doesnt decrease with age, as GFR does)
C. BUN (10-20 mg/dL) - normally 10:1 BUN:Cr; blood urea nitrogen
- disproportionately increased in volume depletion, GI bleeding, high protein diet, catabolic state, corticosteroid use
- disproportionately decreased in low protein diet, liver disease, malnutrition, SIADH
- CKD - sustained and irreversible decrease in GFR
- progressive once creatinine (normally 0.8-1) is 3+ or GFR is <25 ml/min
A. Markers of kidney damage (1+) - albuminuria, abnormalities in urine sediment (eg casts), abnormal electrolytes, kidney transplant
B. Decreased GFR < 60 (stage 3 CKD); (<15 is kidney failure)
[Chronic Kidney Disease]
1. Describe steps in the progression of CKD
A. Major causes
2. Describe how to slow or prevent progression
- CKD Progression
A. Initiation - Major causes (similar to AKI)
- chronic glomerulopathies
- diabetic nephropathy
- obstruction
- hypertension
- polycystic kidney disease
- systemic vascular disease
B. Progression - functional, structural, metabolic adaptations independent of initial injury lead to continued decline in function
- secondary glomerular injury e.g focal and segmental glomerulosclerosis (FSGS), proteinuria, HTN, decreased GFR
C. hypertrophy and hyperfunctioning of the remaining nephrons –> ultimately they stop working –> decreased GFR, scarring
D. fewer nephrons until you progress to ESRD - Prevent progression:
- treat HTN - esp ACEI or ARB (if DMII)
- dietary protein restriction
- glucose control in DM
- prevent AKI (risk factor for loss of kidney function)
- treat metabolic acidosis (correct HC03- back to normal) - slows decline in GFR
- treat hyperphosphatemia, hyperlipidemia, smoking cessation
[Chronic Kidney Disease]
Symptoms and Clinical signs of CKD and reasoning behind
MAD HUNGER
Metabolic Acidosis - ↓ HC03- regeneration
Dyslipidemia (↑ triglycerides) - compensation for proteinuria
Hyperkalemia - associated with acidosis
Uremia - nausea/vomiting, pericarditis, asterixis, encephalopathy, platelet dysfunction
Na/H20 retention –> edema, CHF, HTN
Growth retardation and developmental delay –> failure to thrive
EPO failure –> anemia (fatigue)
Renal osteodystrophy
+
- uremic pruritus - phosphate deposits in skin
- Restless leg syndrome - due to malnutrition, hyperPTH, Vitamin D deficiency
- peripheral neuropathy
[Chronic Kidney Disease]
Describe complications of and adaptations to nephron loss in CKD
1. Na+
2. Dilution and concentrating ability
Adaptations
- Sodium - normal FENa < 1%; with ↓ GFR, FENa increases (due to ANP) –> maintains sodium and water balance
- have to restrict sodium intake, but bc conservation of Na+ impaired –> can get volume depletion if you restrict too much - Dilution and concentrating ability - lower free water clearance (don’t filter as much) –> can develop hypervolemic hyponatremia with increased water intake
- or develop hypovolemic hypernatremia with decreased water intake
- reduced ability to concentrate urine, but fixed concentrating defect (bc of urea diuresis per nephron) –> osmolality ~300
- increased nocturia bc of loss of concentrating ability
[Chronic Kidney Disease]
Describe complications of and adaptations to nephron loss in CKD
3. K+
4. Acid base
- Potassium K+
- hyperkalemia develops late in course of CKD, more likely when mediators of excretion are impaired eg urine flow, aldosterone (Type 4 RTA)
- ↑ likelihood hyperkalemia with: constipation (interferes with gut K+ excretion), ↑ catabolism (eg rhabdo), drugs (K+ sparing diuretics, ACEI, ARB, NSAIDs,TMP, tacrolimus, heparin) - Acid base
- metabolic acidosis common when GFR <25
- ↓ nephron mass –> ↓ ammonium secretion in PCT –> ↓ HC03- retention in PCT (bc for each NH4+ excreted in urine, 1 HC03- is regenerated and returned to blood)
- ↓ excretion of titratable acids (phosphates, sulfates, urates) –> leads to high Anion Gap, acids buffered by HC03- and bone
- maintain HC03- in normal range with sodium bicarbonate (baking soda)
[Chronic Kidney Disease] Describe complications of and adaptations to nephron loss in CKD 5. Bone and mineral metabolism A. Osteitis fibrosa cystica B. Osteomalacia
- Bone and mineral metabolism
- mineral and bone disorder (MBD) - systemic disorder; frequently asymptomatic but can cause joint pain and stiffness, fractures, muscle weakness
- secondary hyperparathyroidism: ↓ GFR –> ↓ PO43- excretion (PCT) and ↓ Ca2+ reabsorption (DCT) –> stimulate PTH release from chief cells –> compensates until enough renal mass is loss –> hyperphosphatemia and hypocalcemia
A. Osteitis fibrosa cystica - most common, due to secondary hyperparathyroidism –> osteoclast stimulation –> bone resorption to release Ca2+ –> loss of bone mass + subperiosteal lesions
B. Osteomalacia - ↓ osteoid mineralization due to ↓ calcitriol (activated in the kidney) –> ↓ Ca2+ absorption in gut –> worsens hypocalcemia
- treat hyperPTH by correcting hypocalcemia, dietary P04 control, phosphate binders
[Chronic Kidney Disease] Describe complications of and adaptations to nephron loss in CKD 6. Anemia 7. Cardiovascular 8. Uremia
- Anemia (low Hb, Hct) - universal, develop normochromic, normocytic anemia when Cr>2 mg/dl
- due to ↓ EPO production by kidney peritubular interstitial cells
- folate and B12 deficiencies
- treat with EPO stimulating agent, maintain iron stores - Cardiovascular - major cause of mortality
- HTN, LVH, CHF (edema due to salt and water retention)
- asymptomatic pericarditis - must start dialysis - Uremia - abnormally high levels of waste products in the blood
- manifestation of severe kidney failure
- accumulation of organic waste products normally cleared by kidney
- hundreds of toxins can accumulate –> affect every system in body –> nausea/vomiting, anorexia and protein calorie malnutrition, growth retardation, encephalopathy and peripheral neuropathy, pericarditis, pallor/bruising, anemia, insulin resistance, muscle weakness/restless leg syndrome, infertility/amenorrhea
↑ BUN, Cr, ↑ P04, ↓ Ca2+
[Nephrolithiasis]
- Risk factors for kidney stones
- Symptoms
- Formation of kidney stone
- Risk factors - personal history, family history, white, diabetes, obesity, metabolic syndrome, vasectomy
- grapefruit juice and soda increase risk; coffee, tea, beer, wine decrease risk (diet plays a big role)
- decreased dietary calcium and urine volume increase risk
- most effective way to prevent is to drink water - Symptoms - unilateral flank tenderness, colicky pain (starts/stops abruptly) radiating to groin, gross hematuria
- Formation - supersaturatable state of chemicals in urine –> nucleation (chemicals come out of urine and form a nidus) –> crystals grow and aggregate to form a stone –> gets dislodged and gets into urine
- Randall’s plaques - deposits of calcium phosphate in interstitium of kidney –> serve as anchor for formation of stones –> breaking free from renal papillae leads to symptomatic stones
[Nephrolithiasis] Describe types of kidney stones incl risk factors, treatment 1. Calcium oxalate A. Risk factors i. hypercalciuria ii. hypocitraturia iii. hyperoxaluria iv. hyperuricosuria B. Treatment
- Calcium oxalate - monohydrate or dihydrate forms
- most common type of kidney stone
- monohydrate form is dumbell-shaped –> associated with ethylene glycol poisoning
- dihydrate form is envelope shaped
A. Risk factors:
i. hypercalciuria - idiopathic, treat with thiazides (inhibit Na/Cl NCC cotransporter –> promote Ca2+ reabsorption –> lower urine Ca2+ levels
ii. hypocitraturia - citrate complexes with Ca2+ and decreases likelihood of it precipitating out
- due to metabolic acidosis (RTA, diarrhea), increased dietary protein
iii. hyperoxaluria - oxalate binds Ca2+ and prevents its absorption; hyperoxaluria due to ↑ intestinal absorption –> small bowel disease (IBD, resection), decreased degradation of oxalate by Oxalobacter formigenes
- or increased oxalate production (Rare)
iv. hyperuricosuria - high levels of uric acid –> creates nidus upon which calcium salts can accumulate
- due to high purine diet (red meat)
v. systemic disease (hyperPTH, Type 1 distal RTA)
B. Treatment - hydration! DASH diet
i. hypercalciuria - thiazides, low sodium diet, reduce non-dairy animal protein intake, do NOT restrict dietary calcium
ii. hypocitraturia - treat with potassium citrate, OJ»lemonade
iii. hyperoxaluria - treat with reducing dietary oxalate (spinach, chocolate), pyrodoxine, Ca2+ supplements
iv. hyperuricosuria - reduce purine intake, treat with hydration, alkalization via potassium citrate, allopurinol
