Exam 3: Renal Pathophysiology Flashcards
Top two causes of renal failure:
Diabetes
HTN
Endocrine functions of kidneys:
EPO secretion
Vitamin D activation
Role of Vitamin D:
Cofactor for intestinal calcium absorption
Severe renal impairment occurs at this % of nephrone damage:
75-90%
Substances not reabsorbed from the tubules:
Urea
Creatinine
Substances partially secreted into the tubules according to body’s needs:
K+
Cl-
Na+
Substances completely reabsorbed in the proximal tubule:
Glucose
Proteins
Amino acids
HCO3- concentration in the filtrate drops at the ______ due to:
Distal tubule; switch to phosphate/ammonia buffers
Three aspects of tubuloglomerular feedback:
- Baroreceptors in the afferent arteriole inhibits renin when pressure is ↑
- Stimulation of β1 receptors causes renin release
- Macula densa sensing ↑ NaCl inhibits renin release
Glucose transporter on apical side of renal epithelium:
SGLT2
The point at which the tubule cannot reabsorb any further glucose is called:
Renal threshold
HCO3- is reabsorbed via this process:
Combines with H+ in the tubule to form H2CO3, which dissociates to CO2 and water, which can cross the membrane
Renal compensation for acidosis:
More H+ excretion
Forming HCO3- via glutamine metabolism
Renal compensation for alkalosis:
Excretion of filtered HCO3-
Electrolyte sequelae of renal compensation for acidosis and mechanism:
Hyperkalemia due to inhibition of the K+ out/H+ in pump on the apical membrane
Effects of ADH on the nephron:
Binds to V2 receptor on basolateral membrane; ↑cAMP activates aquaporin 2 which allows 3 H2O across the apical membrane
Diabetes insipidus is caused by:
Insufficient ADH
S/s of DI:
Large volumes of dilute fluid excreted into urine; severe fluid imbalanes
Nephrogenic diabetes insipidus is:
When collecting tubules are unresponsive to ADH
Three conditions that cause renin release:
↓ renal blood flow
↓ serum sodium
Activation of β1-adrenergic nerves
Condition for aldosterone and angiotensin II release:
Renin release
Condition for natriuretic peptide release:
Overstretch of atrial cells due to excess blood volume
Actions of natriuretic peptides:
Inhibits actions of angiotensin II
Loss of Na+ and water in urine
Condition for urodilatin release:
Distal/collecting tubule identify increased circulating volume
Actions of urodilatin:
Similar to natriuretic peptides; inhibit Na+/H2O reabsorption
How do ACE inhibitors act as diuretics?
Inhibit formation of angiotensin II and aldosterone, which work to retain water
How do loop diuretics work?
Block the Na+/K+/2Cl- pumps in the aloH
How do thiazide diuretics work?
Block Na+ reabsorption
Types of potassium-wasting diuretics:
Osmotic
Loop
Thiazide
Types of potassium-sparing diuretics:
Aldosterone-blocking agents
Most useful lab studies to evaluate kidney function:
Urinalysis
Serum creatinine
BUN
GFR tests
24-hour urine sample good for:
Evaluating substances that are secreted in varying amounts throughout day
Abnormal urine odor:
Ammonia smell (due to bacteria)
Normal color in urine is due to:
Urochrome pigments
Brown or bright red urine is due to:
RBCs (hematuria)
Cloudy urine is due to:
WBCs (infection)
Dark yellow or orange urine is due to:
Concentration
Excess epithelial cells in the urine indicate:
Inflammation/injury in the nephron (cells sloughing off lining of tubule)
WBC casts in the urine are associated with:
Renal infections (pyelonephritis)
RBC casts in the urine are associated with:
Inflammation of the glomerulus (glomerulonephritis)
Epithelial casts in the urine are associated with:
Sloughing of tubular cells (acute tubular necrosis)
Normal creatinine level:
0.7 to 1.5 mg/dl
Elevated creatinine indicates:
Increased rate of muscle breakdown or decrease in renal function
Urea is:
An end product of protein metabolism that’s excreted primarily by the kidney
Normal urea level:
10-20 mg/dl
Elevated urea level indicates:
Decrease in renal function or fluid volume
Increased catabolism/dietary protein intake
Most accurate way to measure GFR:
Inulin clearance test
Define azotemia:
Elevation of BUN/Cr levels, related to decrease in GFR
Define uremia:
Elevation of urea in blood
Define pyuria:
Presence of leukocytes in urine
Five categories of intra-renal disorders:
Congenital Neoplastic Infectious Obstructive Glomerular
Describe pain caused by intrarenal d/o:
Felt at CVA
Dull, constant character
May be felt through out T10-L1 dermatomes
Agenesis is:
Lack of kidney development in fetus
Bilateral vs. unilateral agenesis:
Bilateral: not compatible with life
Unilateral: functional kidney hypertrophies to compensate
Hypoplasia can lead to:
Pediatric ESRD if severe enough
Two types of cystic kidney disease and the population they present in:
Autosomal recessive: kids
Autosomal dominant: adults
ADults
Genes involved in autosomal dominant cystic kidney diseases:
Chromosome 16 –> PKD1 (85%!)
Chromosome 4 –> PKD2
Role of PKD1:
Supports Ca2+ channel in renal epithelium
Role of PKD2:
Codes for the Ca2+ channel involved
Pathogenesis of cystic kidney disease:
↓ Ca2+ in cell and ↑ cAMP leads to cysts and reduction of kidney function
Extra-renal impacts of cystic kidney disease:
Other organs (esp. liver) can have cysts
S/s of cystic kidney disease:
↓ GFR
Inability to concentrate urine
HTN
Pain (most common)
Dx of cystic kidney disease:
Genetic hx and ultrasonography
Tx of cystic kidney disease:
Supportive; BP control and managing renal failure
Parts of the kidney affected by renal cell carcinoma:
Cortex
PCT
Risk factors for renal cell carcinoma:
Smoking
Obesity
HTN
Family hx
S/s of renal cell carcinoma:
Asymptomatic until advanced
CVA tenderness
Hematuria
Palpable mass
Tx of renal cell carcinoma:
Nephrectomy
Metastases of renal cell carcinoma are:
Resistant to radiation, immunotherapy, chemotherapy
Physiological protective measures against renal infection:
Acidic pH
Urea present in urine
Secretions (men: prostatic, women: urethral)
Unidirectional urine flow
Most common cause of acute pyelonephritis:
Ascending infection from lower urinary tract
Dx of acute pyelonephritis:
WBC casts in urine
Tx of acute pyelonephritis:
Prompt abx
Pathogenesis of chronic pyelonephritis:
Reflux or obstructive process –> urine stasis
Chronic inflammation causing scarring/nephron damage
S/s of chronic pyelonephritis:
Abdominal/flank pain
Fever
Malaise
Anorexia
Dx of chronic pyelonephritis:
Renal imaging
Tx of chronic pyelonephritis:
Correct the underlying process
Extended abx tx
Common causes of obstructive renal disease:
Stones (most common)
Tumors
Prostatic hypertrophy
Strictures of ureters/urethra
Sequelae of complete obstruction:
Hydronephrosis ↓ GFR Ischemic kidney damage d/t ↑ intraluminal pressure Acute tubular necrosis Chronic kidney disease
Most renal calculi are composed of:
Calcium crystals
Non-calcium stones made of:
Uric acid
Struvite
Cystine
S/s of renal calculi:
Intense, abrupt, radiating renal colic pain
N/V
Diaphoresis
Hematuria
Dx of renal calculi:
CT scan
Tx of renal calculi:
Fluids (> 2L/day) Lithotripsy/endoscopy Ureteral stenting Ureteroscopy Pain medication!! Dietary changes depending on type of stone
Three types of glomerular cells:
Endothelial
Mesangial
Podocytes
Primary vs. secondary glomerular disorders:
Primary: only the kidney involved
Secondary: results from other diseases, conditions, meds
Secondary glomerular disorders:
Goodpasture syndrome
Systemic lupus erythematosus
Diabetic nephropathy
Goodpasture syndrome in the kidney:
Antibodies vs. the glomerular basement membrane (also affects lungs)
Systemic lupus erythematosus in the kidney:
Antibody complexes settle into the mesangial region of the glomerulus
Diabetic nephropathy pathogenesis:
Glucose binds to protein and complex sticks to endothelial cells, causes damage
Three ways to classify glomerular disorders:
Diffuse vs. focal (all vs. some glomeruli)
Global vs. segmental (all vs. some parts of glomeruli)
Membranous vs. sclerotic (thickening of capillaries vs. scarring)
Three sites of deposition in glomerular disorders:
Mesangial (SLE)
Subendothelial
Subepithlial (Goodpasture)
S/s of glomerular disorders:
Hematuria Proteinuria** (classical) Abnormal casts ↓ GFR Edema HTN
Nephrotic syndrome characterized by:
Protein loss in urine: 3 - 3.5gm in 24 hrs
Nephritic syndrome characterized by:
Mild to moderate proteinuria, hematuria, RBC casts (nephrotic syndrome + inflammation)
Glomerulonephritis is:
An immune response to a variety of triggers that produces inflammation in the glomeruli
Glomerulonephritis is more common in:
Men
Pathogenesis of acute glomerulonephritis:
Immune cells are attracted to inflammation in glomeruli, resulting in lysosomal degradation of the basement membrane
GFR falls in acute glomerulonephritis due to:
Contraction of the mesangial cells –> decreased area for filtration
S/s of acute glomerulonephritis:
Proteinuria Oliguria Azotemia Edema HTN
Tx for acute glomerulonephritis:
Steroids
Plasmapheresis
Dietary, fluid mgmt
HTN mgmt
Pathogenesis of postinfectious acute glomerulonephritis:
Infectious agent causes antibody-antigen deposition (IgG) in the glomerulus –> proliferation of mesangial cells –> lesions
Infections that lead to postinfectious acute glomerulonephritis:
Impetigo and throat infections with group A β-hemolytic strep
Group in which postinfectious acute glomerulonephritis typically is found:
Children in developing countries
S/s of postinfectious acute glomerulonephritis:
Smoky or coffee-colored urine
Pathogenesis of IgA nephropathy (Berger disease):
Post-URI or GI viral infection, IgA complex deposition in mesangial cells –> mesangial injury
S/s of IgA nephropathy (Berger disease):
Proteinuria
Hematuria in 1-2 days
Typically IgA nephropathy (Berger disease) is seen in:
Adults
Difference between post-infectious and IgA nephropathy (Berger disease) glomerulonephritis:
Post-infectious: IgG, will see edema and HTN
Berger: IgA, NO edema/HTN
Pathogenesis of chronic glomerulonephritis:
Progressive course of proliferative, membranous lesions (glomeruli replaced with collagen)
Sclerosis/fibrosis of kidney
S/s of chronic glomerulonephritis:
Proteinuria
-/+ hematuria
Slowly declining renal fxn
Tx of chronic glomerulonephritis:
Supportive interventions (fluid mgmt, etc) until dialysis/transplant necessary
Pathogenesis of nephrotic syndrome:
Increased glomerular permeability to proteins; proteinuria leads to hypoalbuminemia; edema occurs d/t ↓ osmotic pressure in blood
Causes of nephrotic syndrome:
Minimal change disease
SLE
DM
S/s of nephrotic syndrome:
Proteinuria
Edema** (most common)
HLD, hypercoag d/t ↑ liver fxn (due to ↓ albumin)
Tx of nephrotic syndrome:
Diuretics
Lipid-lowering agents
AntiHTNs
Immunosuppression/modulation
Pathogenesis of minimal change disease:
Triggered by allergic or immune condition
Foot processes of glomerular podocytes fuse together; decreased production of basement membrane anions
S/s of minimal change disease:
Edema
Nephrotic levels of proteinuria
Hypoalbuminemia
Tx of minimal change disease:
Corticosteroids
Acute renal failure is:
Sudden reduction in kidney function
ARF causes:
Fluid/lyte/acid-base imbalances
Retention of waste products
↑ serum Cr
↓ GFR
Causes of pre- vs. intra- vs. post-renal:
Pre: ↓ renal perfusion
Intra: parenchymal renal disease
Post: obstruction
How can BUN/Cr be used to dx cause of ARF?
Only if BUN is elevated - ratio will determine location of cause
Normal BUN/Cr ratio:
10-20
Normal BUN:
8-10 mg/dl
Normal Cr:
0.6 - 1.2 mg/dl
BUN/Cr ratio > 20 indicates:
Pre-renal ARF; urea has more time to be reabsorbed
Bun/Cr ratio < 10 indicates:
Intra-renal ARF; tubules failing, reabsorbing less urea
Bun/Cr ratio 10-20 indicates:
Post-renal ARF
BUN and creatinine are each handled in the nephron in this fashion:
BUN: filtered in glomerulus, reabsorbed by tubule
Cr: filtered in glomerulus, secreted in filtrate
Causes of prerenal ARF:
Any sudden/severe drop in BP or interruption of blood flow
Hypovolemia, HoTN, heart failure Renal artery obstruction Fever/vomiting/diarrhea Burns Diuretics, edema, ascites
Drugs that can cause prerenal ARF:
ACE inhibitors, angiotensin II blockers, NSAIDs
Low GFR in prerenal ARF leads to:
Oliguria
High urine SG/osmolarity
Low urine Na+
Azotemia
Prolonged prerenal ARF leads to:
Acute tubular necrosis
Tx of prerenal ARF:
Improve renal perfusion via fluid replacement or dialysis
Pathogenesis of post-renal ARF:
Obstruction distal to the kidney causes elevated pressure all the way back to the Bowman capsule which impairs glomerular filtration
Prolonged post-renal ARF leads to:
Acute tubular necrosis and irreversible kidney damage
Early phase of post-renal ARF:
Reflex adaptation to maintain GFR: afferent arteriole dilation
Lasts 12-24 hours
Late phase of post-renal ARF:
Afferent arteriole dilation ceases after 12-24 hours
Renal perfusion, glomerular blood flow, and GFR drop
Oliguria/anuria
Ischemia/nephron loss
Recovery phase of post-renal ARF:
Pre-renal vessels relax
Perfusion restored
GFR increases in surviving nephrons
Dilation may be permanent!
Causes of acute tubular necrosis:
Nephrotoxic insults (contrast media) Ischemic insults (sepsis)
Vascular pathogenesis of intrarenal ARF:
Renal blood flow decreases –> hypoxia, vasoconstriction
Tubular pathogenesis of intrarenal ARF:
Inflammation/reperfusion injury –> casts, obstruction of flow, tubular backleak
Three phases of ATN:
Prodromal phase
Oliguric phase
Post-oliguric phase
Prodromal phase of ATN:
Insult to the kidney has occured
Oliguric phase of ATN:
~1-2 weeks (up to 8 weeks)
UOP 50-400 ml/day
Progressive uremia
Decreased GFR/hypervolemia
Post-oliguric phase of ATN:
Diuresis Impaired tubular function Azotemia Fluid volume deficit until recovery 2-10 days, up to 1 year
Prognosis for acute renal failure:
Good in otherwise healthy patients if underlying issue is corrected
Predictors of mortality from ARF:
Oliguria, severe illness, MI, stroke, seizure, immunosuppression, mechanical ventilation
Progression of chronic renal failure:
Chronic kidney disease –> chronic renal failure –> end-stage renal disease
CRF stage which requires dialysis:
ESRD
Comorbidities linked to CRF:
HTN, DM
Definition of CRF:
Kidney damage/impairment of 3 months or more
GFR < 60 for 3+ months
Kidneys compensate until this % of damage:
75-80%
Stage 1/2 CRF:
Minimizing risk factors
Stage 3 CRF:
Symptoms appear, tx may be needed
Stage 4 CRF:
Plan for dialysis/transplant
Stage 5 CRF:
Renal replacement tx needed for survival
Role of angiotensin II in renal injury:
Vasoconstriction increases GFR
Pathogenesis of CRF:
Renal injury –> loss of nephrons, vasoconstriction from angiotensin II
Glomerular capillary hypertension, over time, leads to increased permeability/filtration
Proteinuria, increased protein reabsorption
Tubular/interstitial inflammation, fibrosis, scarring
Creates systemic HTN which worsens glomerular capillary HTN
Risk factors for CRF:
DM HTN Pyelonephritis (recurrent) Glomerulonephritis Polycystic kidney disease Family hx Toxin exposure Age > 65
Management of CRF:
BG control
ACEIs or ARBs to reduce proteinuria
Management of HTN
Management of metabolic acidosis:
Mild (7.3 to 7.35) no tx
< 7.3 may take NaHCO3
CV effects of CRF:
Hypervolemia/HTN
Atherosclerosis
Heightened RAAS/SNS activity
Metabolic effects of CRF:
Uremic syndrome/impaired healing
Hyperkalemia
Metabolic acidosis
Electrolyte imbalances in CRF:
Hyperkalemia
Hypermagnesemia
Hyperphosphatemia
Bone/mineral disorders from CRF:
Elevated phos/PTH causes altered bone metabolism
Kidneys unable to reabsorb calcium
Hematological effects of CRF:
Lack of EPO –> anemia
Uremia shortens RBC lifespan
Blunted immune response
Primary reason to initiate dialysis in CRF:
Uremia or hyperkalemia unresponsive to other txs
Pathogenesis of renal-related HTN:
Renin release by injured kidney -or- hypervolemia due to renal mishandling of sodium
Pulmonary impacts of CRF:
Chronic pulmonary edema
Micturition mediated by:
Pons
Gravity/pressure
Peristalsis
CNS
Pons’ role in micturition:
Relaxation of internal sphincter
Contraction of bladder
Cerebral cortex’s role in micturition:
Inhibition via conscious control of external sphincter
ANS role in micturition:
SNS: L1-2 allow relaxation and filling
PSNS: S2-4 cause bladder contraction, relaxation of internal sphincter
Incontinence is normal when:
Never!
Urge incontinence is:
Involuntary leakage along with/after feeling the need to void
Causes of urge incontinence:
Bladder infection Radiation tx Tumors Stones CNS dmg Idiopathic
Causes of stress incontinence:
Weakening of pelvic muscles or urethral sphincter deficiency
Causes of overflow incontinence:
Obstruction of urethra
Under/inactive detrusor
Types of enuresis:
Primary nocturnal enuresis
Secondary enuresis: after 6 mo dry
Monosymptomatic nocturnal enuresis: no other signs of lower UTI malfunction
Nonmonosymptomatic nocturnal enuresis: urgency/frequency/daytime incontinence as well
Pathogenesis of enuresis:
ADH deficiency
Overactivity of destrusor
Immature arousal mechanisms
Manifestations of vesicoureteral reflux:
Recurrent UTI
Voiding dysfunction
Renal insufficiency
Hypertension in children
Ureterocele is:
Cystic dilation at distal end of ureter
Manifestations of ureteroceles:
Hydronephrosis UTIs Voiding dysfunction Hematuria Urosepsis Failure to thrive
Tx of ureterocele:
Surgical intervention
Most cases of cystitis are from:
Infection originating in urethra
Common minerals that make urinary tract stones:
Calcium
Oxalate
Phosphate
Uric acid
Effect of dietary calcium on kidney stones:
Prevents them via binding of oxalate
Endocrine dysfunction associated with kidney stones:
Hyperparathyroidism
Effect of hydronephrosis on kidney structure:
Dilation of pelvis/calyces
Thinning of renal parenchyma
