Kidney Patho Flashcards
Definition
Acute Kidney Injury (AKI)
Acute onset (hours to days)
3 types
1. pre-renal
2. intra-renal
3. post-renal
Increase in serum creatinine
Decrease urinary output
OR
BOTH
Definition
Oligouria
urinary output < / = 30cc/hour
Definition
Azotemia
Increased serum creatinine
Increase serum blood urea nitrogen (BUN)
BUN:Cr ratio > 20:1
*inability kidney to filter waste products (nitrogenous waste)
Definition
Uremia
Systemic signs and symptoms resulting from loss of kidney function (inability filter waste)
3 categories of acute kidney injury
- pre-renal
- before the kidney
- blood volume
- cardiac output
- obstruction blood flow - intra-renal
- inside the kidney - post-renal
- after the kidney
- obstruction of urine flow
Pre-renal AKI
Definition
Trigger –> decrease renal blood flow –> decrease glomerular perfusion, filtration
Triggers include
1. obstruction
2. decrease blood volume - hemorrhage, dehydration, third spacing
3. decrease cardiac output
4. decrease renal blood flow
Urinalysis and serum indicators
Pre-renal AKI
Decrease renal blood flow sensed by juxtaglomerular cells
Release renin and activation RAAS compensation
Reabsorption sodium, water, urea
- BUN:Cr > 20:1
Oliguria (< 30ml/hour)
High urine osmolality > 500mOsm/kg
- aldosterone promotes water reabsorption
Decreased excreted sodium
- FEna = Na excreted / Na filtered < 1%
Decrease glomerular filtration
increase creatinine, increase BUN
Most common cause of pre-renal AKI
sepsis
Compensatory systems
Decreased renal blood flow
- SNS
- NE and E released
- vasoconstriction - HPA axis
- Cortisol release
- vasoconstriction - ADH
- anti-diuretic hormone release
- reabsorption water - RAAS pathway
- vasoconstriction
- retention sodium and water
- reabsorption urea
Drugs that potentiate pre-renal AKI
Vasoactive medications
- dopamine
- ACE inhibitors
- ARBs
NSAIDS & Radioactive contrast dyes
- decrease blood flow to kidney
Definition
Intra-renal AKI
INtra-renal AKI
- intrinsic
- direct damage to the renal parenchyma
- results in nephron dysfunction
Causes of Intra-renal AKI
- Glomerulus: Glomerulonephritis
- Tubules: acute tubular necrosis
- Vasculature: infarct, thrombosis (pre-renal progresses to intra-renal)
- interstitial disease: infection, tumors (acute nephritis)
Most common cause of intra-renal AKI
Acute tubular necrosis (ATN)
Glomerulonephritis
Definition
Injury to the glomerulus
Leads to inflammation of the glomerular capillaries and destruction of the glomerular membrane
Acute or chronic
Nephrotic Syndrome
Definition
Results from injury to the glomerulus
Unable to prevent filtration of proteins
Results in >/= 3.5g / day of protein in urine
Pathophysiology
Acute Tubular Necrosis
- Injury: nephrotoxins
- Ischemia
Nephrotoxins
- direct damage to tubular epithelial cells
Ischemia
- Lack of blood supply
Tubular epithelial cell dysfunction
- Cannot reabsorb
- High urine sodium (> 30mmol/L)
- High FEna (Na excreted / Na filtered) > 1 %
- Low urine osmolality (<400mOsM/L)
- Low urine specific gravity (1.010-1.012)
- Low BUN:Cr ratio < 15:1 - Cannot secrete
- hyperkalemia
- metabolic acidosis (cannot secrete H+ ions) - Increase Tubular pressure = decrease GFR
- necrotic cells slough off
- plug the tubule
- formation brown casts in urine
- tubule opposes filtration pressure in artery
- decrease GFR
- increase serum creatinine, increase serum urea (azotemia)
- decrease urinary output (oliguria)
Factors required for reversible intra-renal AKI
- ischemia is not prolonged
- basement membrane is present
- tubular epithelial cells regenerate
Definition
Post-Renal AKI
Obstruction of urinary flow
Backs up into the renal pelvis
increase intra-tubular pressure
Decreases filtration
Causes of Post-Renal AKI
tumour
stones
trauma
strictures
prostate
neurogenic bladder
*< 5% of AKI
4 stages to the clinical course of AKI
- Initiation (onset)
- oligouria
- increase Cr
- increase BUN
-*reversible before damage at this stage - Extension
- ischemia
- inflammation - maintenance phase (oliguric phase)
- initiation event resolved
- injury established by extension phase (ischemia, inflammation)
- 10-14 days (healing inflammation)
- longer duration is poor prognosis - recovery phase (polyuria)
- most recovery within 3 weeks, can take up to 1 year for full recovery of function
Clinical Signs and Symptoms
Oliguric phase (maintenance phase) AKI
Oligouria
- decrease U/O
- normal SG (cannot reabsorb water)
- high urine sodium (cannot reabsorb sodium)
- low urine osmolality (cannot reabsorb water)
- BUN:Cr < 15:1
- FEna > 1%
Urinalysis
- RBC, protein (damage glomerular membrane)
- brown casts (tubular necrosis)
- WBC (inflammation)
FVO
- decrease GF = fluid retention
- edema, hypertension, heart failure
- pulmonary edema, crackles
- bounding pulses, jugular venous distention
metabolic acidosis
- tubules cannot excrete H+
- tubules cannot reabsorb HCO3-
- decrease pH
hyponatremia
- tubules cannot reabsorb sodium
- sodium excrete in urine
- hyponatremia serum
hyperkalemia
- tubules cannot excrete potassium
- hyperkalemia in serum
- cardiac dyrhythmias
hypocalcemia, hyperphosphatemia
- kidney cannot activate vitamin D
- cannot absorb calcium in GI
- PTH released increase bone reabsorption - increase phosphate in blood
Azotemia and neurological symptoms
- increase waste, creatinine, BUN
- fatigue, stupor, coma, confusion
Clinical Signs and Symptoms
Recovery (polyuric) phase
Kidney able to excrete waste (unable to concentrate urine)
result is polyuria > / = 3-5 L / day urine
Recovery function 1-3 weeks , up to 1 year
Risk in Recovery phase
dehydration
hypovolemia
electrolyte imbalances
Management of AKI
Hospital admission
- electrolytes
- monitor and manage sodium, potassium, calcium, phosphate - fluid
- monitor fluid volume overload / dehydration
- replacement / diuretics / dialysis - blood pressure and cardiac output = kidney perfusion
- dietary changes
- fluid volume restrictions
- sodium or potassium restrictions or supplements
- increase protein - dialysis
- acidosis, FVO, hyperkalemia - medication renal dose adjustments
Prevention of AKI
Renal dose adjustments for medications and age
Fluid to wash out nephrotoxic medications
Maintaining renal perfusion
- treating infections (sepsis)
- hydration and prevention dehydration
- monitoring fluids post operatively, trauma, burns
- maintaining healthy blood pressure and cardiac output
- maintaining normoglycemia
- maintaining healthy liver
Immediate treatment of urinary obstructions
- BPH, tumours, stones
Definition
Chronic Kidney Disease
Also known as
- renal insufficiency
- chronic renal failure
chronic, irreversible loss of kidney function
- nephron destruction
change in structure or function present for > 3 months
Classification
Chronic Kidney disease
- GFR
- Albuminuria
GFR
Stage 1, normal, > 90ml/min
stage 2, mild, 60-89ml/min
stage 3, moderate, 30-59ml/min
stage 4, severe, 15-29ml/min
stage 5, end stage renal disease < 15ml/min
albuminuria
stage 1, mild, < 3mg/mmol
stage 2, moderate, 3-30mg/mmol
stage 3, severe, > 30mg/mmol
Definition
Glomerular filtration rate
Amount of blood filtered in mL per minute by the glomerular membrane = number functioning nephrons = kidney function
Factors that affect GFR
Age
sex
height
weight
*serum creatinine
Over-estimation GFR
kidney actively secretes creatinine in addition to creatinine that is filtered at the glomerulus
Clinical ways to assess albuminuria
Urinalysis
- albumin
- creatinine
24 hour urinalysis
- albumin
- creatinine
POCT
- albumin dipstick
Who should be screened for CKD?
Anyone who has risk factors for CKD
- smoking
- diabetes
- hypertension
- hyperglycaemia
- physically inactive
Screen
1. GFR
2. albuminuria
earlier diagnosis = slow progression
Nephropathy secondary to Diabetes Mellitus
Pathophysiology
Clinical signs
- Hyperglycemia
- Inflammation -> scaring -> dysfunction glomerular filtration membrane/tubular dysfunction
hyperglycaemia –> oxidative radicals –> microvascular damage, glomerular filtration membrane damage, epithelial cell damage
glucose -> free radicals -> inflammation -> scaring/fibrosis -> decreased filtration, decreased tubular reabsorption, proteinuria, waste/FVO
Nephropathy secondary to hypertension
- HTN
- renal artery stenosis
- ischemia -> inflammation -> scarring/dysfunction (glomerular filtration membrane, tubular epithelium)
Hypertension –> microvascular damage –> renal artery stenosis –> decreased renal blood flow –> ischemia –> inflammation –> scarring/fibrosis –> damage and reduce glomerular filtration –> ischemia tubular epithelium –> dysfunction
What percentage of kidney function do you see clinical signs and symptoms of CKD manifest?
25% kidney function
Clinical manifestations all body systems
Chronic Kidney Disease (CKD)
Neuro
- confusion, fatigue, HA, sleep disturbances, encephalopathy
Eyes
- retinopathy
Cardiac
- dysrhythmias (hiperkalemia)
- HF
- HTN
- uremic pericarditis
- CAD (dyslipidemia)
Pumonary
- edema (FVO)
- uremic pleurites
GI
- uremic gastritis
- ulcers, hemorrhages
- N/V/anorexia
Integumentary
- urochromes (yellow skin, brown/white nails)
- pruitis uremia
- ecchymosis (loss of clotting factors)
- pale (loss of EPO, RBC, anemia)
MSK
- weakness, numbness, tingling
- fractures
- electrolyte disturbances (hyponatremia, hyperkalemia, hypocalcemia, hyperphsophatemia)
Metabolic
- hyperglycemia
- dyslipidemia
Haematological
- bleeding (loss of platelets, clotting factors)
- infection (loss of blood cells, immunoglobulins)
- decreased response to vaccination
- anemia
Endocrine
- dysmenorrhea, infertility
- loss of libido
Diagnosis
CKD
- history
- clinical signs and symptoms
- GFR and albuminuria (stage of kidney disease)
- urinalysis (casts, RBC, WBC, protein)
- imaging (US, CT, etc.)
Pharmacological Management
Supportive management CKD
Management: HTN
- ACEi (IPRIL) and ARBs (SARTAN)
- renal protective
- slow eGFR decline, slow microalbuminuria
*not effective for end stage
Management: Dyslipidemia
Management: Glucose
Dietary modifications
- plant based proteins
- weight loss (not end stage)
- protein restriction ( not old people )
Vaccinations
- infection risk
Blood products
- anemia
Dialysis
- acidosis
- hyperkalemia
- FVO
- waste products
3 functions of the kidney
- water and electrolyte balance
- acid-base balance
- remove waste
- hormones (EPO, activation vitamin D)
pre-renal AKI
Absolute loss of fluid examples
blood loss
trauma
surgery
diarrhea
vomiting
diabetes mellitus uncontrolled
burns
diuretics
pre-renal AKI
relative fluid loss examples
Hypotension
decreased cardiac output
heart failure
DIstributive shock
sepsis
ascites
pre-renal AKI
renal artery hypo perfusion examples
Emboli
tumour
stenosis
Vasoactive medications
- dopamine
- epinephrine
- NSAIDS
- ARBs
- ACE inhibitors
Pre-Renal AKI
BUN:Cr Ratio
Normal BUN: Cr ratio 20:1
pre-renal AKI
> 20:1
- decrease waste filtration
- urea follows sodium
Example nephrotoxins that cause
intra-renal AKI
aminoglycosides
NSAIDS
heavy metals - lead
ethylene glycol - antifreeze
radiocontrast dyes
myoglobulin
uric acid waste (tumour lysis syndrome)
Glomerular filtration membrane anatomy
3 layers of cells
- endothelial layer (fenestrations)
- basement membrane (selectively permeable, negative charge, pores)
- epithelial layer (podocytes, filtration slits)
Clinical Signs and Symptoms
Early post-renal AKI
Intra tubular pressure decreases glomerular filtration
- increase serum creatinine, BUN
- oligouria
- increase absorption sodium, water, urea
- FEna < 1%
- urine osmolality > 500mOsM/L
Clinical Signs and sympotms
Late post-renal AKI
Back pressure destroys the tubular epithelial cells
mimics intra-renal AKI
- high urine sodium
- low urine osmolality
- FENa > 1%
- BUN:Cr < 15:1
- high urine sodium concentration > 30mmol/L
End of recovery phase
AKI
marked by normalization acid-base balance, electrolytes, fluids
Goal of treatment
AKI
- Remove mechanism of injury
Supportive care to keep patient alive during recovery and correct imbalances
- correct fluid volume
- correct electrolyte imbalances
- correct acid-base imbalances
- monitor and correct HTN, dyslipidemia, hyperglycaemia
- monitor and correct infection, immunosuppression, anemia
- diet changes and supplementation
- renal replacement therapy / dialysis
Goal Treatment
CKI
Correct fluid volume, acid-base, electrolyte imbalances
Correct HTN, dyslipidemia, hyperglycemia
Correct anemia, infection, immunocompromised
protein restriction (exception old, end stage)
weight loss (exception old, end stage)
Dialysis (end stage)
Avoid nephrotoxins
Nephrotic syndrome
Clinical manifestations
- Proteinuria > 3.5 g per day
- loss of albumin (hypoalbuminuria), edema; loss of immunoglobulins (infection); loss of WBC (infection); loss of clotting factors (bleeding) and anti-thrombin (clots) - lipiduria
- fat floating on urine “foamy” - hematuria
- RBC found in urine
- dark brown, tea coloured - Edema
- third spacing, decreased oncotic pressure
- increase RAAS and ADH - Dyslipidemia
- increase TG, LDL, cholesterol
Nephritic syndrome
Clinical manifestations
Proteinuria < 3.5g per day
*most common cause is post-infectious glomerulonephritis
Types of Glomerulonephritis
- acute vs. chronic
- immune vs. non immune
- primary vs. secondary
primary
- direct injury to the glomerulus
- trauma, infection, type II-IV hypersensitivity reactions, clots
secondary
- diabetes mellitus, hypertension etc.
Pathophysiology
Glomerulonephritis
- Immune mediated OR 2. non-immune mediated –> injury to the glomerulus –> inflammation
- deposition inflammatory mediators, auto-immune complexes, complement
- proliferation mesangial cells and endothelial cells –> decrease renal blood flow –> decrease GFR
- inflammation damages epithelial cells (filtration slits) and basement membrane (negative charge) –> loss of selective filtration –> proteinuria, hematuria
- inflammation –> fibrosis –> scaring –> decrease GFR
Result:
oligouria
azotemia (increase creatinine, increase urea)
Post-infectious glomerulonephritis
Clinical symptoms
Prior infection that has since cleared
- staphylococcus
- streptococcus
- HBV/HCV
- varicella virus
Type III hypersensivity reaction (IgM/IgG) deposit in the glomerular membrane –> mesangial proliferation –> decrease RBF –> decrease GFR
Most common cause of nephritic syndrome
proteinuria < 3.5g per day
Explain how creatinine and eGFR are related
estimated GFR = 24 urine creatinine clearance (calculation compared to plasma creatinine)
Creatinine
- filtered = excreted in urine (not reabsorbed)
- slightly overestimated (some secreted)
- reflect kidney function (functional nephrons)
- muscles produce at stable rate (false rhabdomyolysis, malnutrition)
- calculation affected by (age, height, weight, gender)
Intact nephron hypothesis
What is it
What stage of CKD
Stage 2 CKD
Mild
GFR 60-89mL/min
surviving nephrons compensate for loss of nephrons - hyperfunction, hypertrophy - maintain normal fluid balance, electrolytes, acid-base balance
Uremic Syndrome
What is it
What stage of CKD or % kidney function
Systemic signs occur at 25% kidney function
Normal eGFR 90mL/min
Moderate eGFR 30mL/min (stage 3) clinical signs and symptoms appear
Uremic syndrome (stage 5)
Anatomy
Nephron
Renal corpuscle
- bowman’s capsule
- glomerulus
- mesangial cells (macrophages, vasoconstriction afferent arteriole)
Renal tubules
- proximal convoluted tubule
- loop of henle
- distal tubule
Renal tubules
Cells and Function
Proximal tubule
- brush boarder cells
- microvilli increase SA for reabsorption
- high mitochondria for active transport
Distal tubule
- Intercalated cells - H+ excretion, HCO3- absorption (acid base balance)
- Principle cells - sodium and potassium balance, (influenced by macula densa - sodium sensing cells, and aldosterone)
Glomerulus
Cells and function
Mesangial cells
- vasoconstriction of glomerulus capillaries (smooth muscle cell function)
- phagocytosis and release of inflammatory cytokines (monocyte function)
Juxtaglomerular cells
- located around afferent arteriole
- sense decrease in renal blood flow
- release renin in response to beta 1 adrenergic stimulation
Macula densa cells
- located between the afferent and efferent arteriole
- sodium sensing cells of the distal convoluted tubule
Natriuretic peptides
Function
ANP - atrial natiuretic peptide
BNP
release from overstretch of cardiomyocytes
prevention sodium/water reabsorption by kidney
increase diuresis
CNP
released by vascular endothelium from stretch
increase vasodilation afferent arteriole
icnrease GFR
increase diuresis
Renal natriuretic peptide
released by collecting duct stretch
increase vasodilation afferent arteriole
increase diuresis
Hormones produced by the kidney
EPO
- erythropoetin
- juxtaglomerular complex
- sensation hypoxia –> stimulation RBC production
RNP
- renal natriuretic peptide
- released by collecting duct
- increase diuresis
Vitamin D3 activation
- 1,25 dihydroxyvitamin D
- allows for calcium reabsorption
Renin
- release day juxtaglomerular cells in response to low blood flow
- angiotensinogen -> angiotensin I
- angiotensin I –> angiotensin II (ACE)
- Aldosterone
- vasoconstriction
- vascular/cardiac remodeling
- sodium and water reabsorption
5 functions of the kidneys
- Fluid balance, blood pressure
- acid-base balance
- hormones, aldosterone, renin (RAAS), vitamin D (active), urodilantin (diuretic)
- excretion waste (urine)
Anatomy:
Location of the Kidney
T12-L3
retroperitoneal cavity
R kidney lower than L kidney (liver displaces)
Definition Nephron
Measurement of nephron function
Nephron - functional unit of the kidney
Glomerular filtration rate = number of functioning nephrons
- Creatinine (muscle waste product)
- Cystatin C (early kidney damage marker)
- BUN (blood urea nitrogen)
Components of the
Renal Corpuscle
Bowman’s Capsule
Glomerular capillaries
Mesangial Cells (release cytokines, vasoconstriction to maintain RBF, phagocytosis)
3 Layers of the glomerular filtration membrane
- Endothelial cells
- Basement membrane (anionic charge, repels protein)
- Epithelial cells (filtration slits)
Selectively permeable
1. size
2. charge
3. hydrostatic pressure, oncotic pressure
Components of the
Juxtaglomerular apparatus
- Juxtaglomerular cells (produce renin, afferent arteriole)
- Macula densa (sodium sensing cells, between afferent/efferent arteriole)
Components of the
Nephron
- Proximal convoluted tubule
- Descending loop of henle (thick, thin)
- Ascending loop of henle (thin, thick)
- distal convoluted tubule
- collecting duct
Function and cells
Proximal convoluted tubule
Function
- production of primary urine
- reabsorption of solutes
Brush boarder cells
- microvilli, increase SA, reabsorption
- Active reabsorption sodium, secretion hydrogen (Na/H pump)
- water and urea passively reabsorbed (follow sodium)
- cuboidal epithelial cells
FUnction and cells
Descending loop of henle
Function
- concentration and dilution of urine
Cuboidal epithelial cells (THICK)
- active reabsorption sodium
- water passively follows
Squamous epithelial cells (THIN)
- no transport
Function and cells
Ascending loop of henle
Impermeable to water
Active transport sodium reabsorption
Function and cells
Distal convoluted tubule
Function
- Acid base balance
- blood pressure
Principle cells
- production aldosterone
- Na/K pump
- reabsorption sodium, excretion potassium
Intercalated cells
- excretion hydrogen
- reabsorption potassium (H/K pump)
- reabsorption bicarbonate
Function
Collecting duct
Function
- reabsorption / excretion water
- Aquaporins insert via ADH signal
Ureter
Anatomy, cell type
Function
Referred pain location
Cell: smooth muscle, involuntary
Function: connection renal pelvis to bladder, drain urine ; peristaltic contractions
Referred pain: umbilicus (upper ureter), vulva/penis (lower ureter)
Bladder
Anatomy
Function
Anatomy
- detrusor
- trigone
- internal spincter (all smooth muscle, involuntary)
and external spincters (voluntary, SNS, skeletal muscle)
Function
- Micturition reflex (involuntary, PNS, mechanoreceptors stretch 300cc)
Regulation of renal blood flow (RBF)
- Autoregulation
- Hormones
- Nervous system
Autoregulation
- mesangial cells
- maintain GFR regardless of fluctuation blood pressure (normal range)
Hormones
1. RAAS
2. natriuretic peptides
3. sympathetic nervous system (SNS)
RAAS
- renin released by juxtaglomerular cells (low BP, SNS)
- angiotensin II (vasoconstriction systemic, vasoconstriction efferent arteriole, release ADH posterior pituitary)
- aldosterone (reabsorption sodium, water)
Natriuretic peptides
1. urodilantin
- collecting ducts, release in response to stretch
2. ANP (aortic/carotid), BNP (ventricles), CNP (vascular endothelium)
- released in response to stretch
- vasodilation afferent arteriole
- increase GFR and urination
SNS
- Release NE and E
- bind to beta adrenergic receptors on juxtaglomerular cells, release renin
- activation of the RAAS pathway
Stimuli that increases renin release
- hypovolemia (detected at afferent arteriole, low RBF)
- activation SNS and release of NE / E binding beta adrenergic receptors
- prostaglandins (decrease renal blood flow)
- low sodium at collecting duct
Define Net filtration pressure
- hydrostatic pressure
- oncotic pressure
inside and outside the bowman capsule
determines direction of filtrate
Diseases which decrease GFR
Increased Bowman capsule hydrostatic pressure
- tumours
- strictures
- stones
Increased plasma oncotic pressure
- dehydration
- vomitting
- diarrhea
- loss of water, blood becomes high concentration
Loss of glomerular membrane
- diabetes
- sepsis
Renal hormones
- Vitamin D
- activates vitamin D (1, 25 dihydroxyvitamin D)
- absorption calcium, excertion phsophate (GI and kidney)
- bone health
- CKD osteoporosis - erythropoetin (EPO)
- bone marrow formation RBC
- CKD anemia
Function plasma creatinine concentration
serial measurments
differentiate chronic vs. acute kidney injury
Cystatin C function
early detection of decreased GFR
Urine chemistry
Bilirubin = dark orange
urobilinogen = RBC hemolysis
ketones = fat metabolism
glucose = hyperglycemia
sodium - increase or decrease with disease
potassium - increase or decrease with disease
protein - glomerular dysfunction, should be negative
Microscopic urine
- bacteria
- RBC
- WBC
- crystals (stones)
- Fat (nephrosis)
- casts
