Renal 1 Flashcards
1
Q
What are the functions of the kidneys? Examples?
A
Excretory
Filtration, secretion, (reabsorption), excretion
Endocrine
Renin, prostaglandins, kinins, erythropoeitin
Metabolic
Vitamin D activation, gluconeogenesis, insulin metabolism
2
Q
What is renal functionsummarized as? (Roles of the kidney)
A
excretion + endocrine + metabolic functions
3
Q
What are the excretory functions of the kidney?
A
Regulate fluid, electrolyte, and acid-base balance
Remove metabolic waste products & foreign chemicals from blood for urinary excretion
4
Q
How are the excretory functions of the kidney accomplished?
A
Filtration
Reabsorption
Secretion
5
Q
Describe glomerular filtration
A
Blood enters the glomerulus through the afferent arteriole
Glomerular filtration: Blood is filtered by hydrostatic pressure through the capillaries that form the glomerulus into the Bowman capsule (Non-selective process)
Blood leaves the kidney through the efferent arteriole
6
Q
How much of filtrate is composed of the plasma? Composition of Filtrate (Basic)
A
The filtrate is composed of ~20% of the plasma entering the glomerulus
Composed mainly of fluids, electrolytes, small molecules
Excludes proteins and large molecules (e.g., blood cells, albumin)
7
Q
Composition of Filtrate (Specific). Exceptions?
A
Glucose
Amino acids
(Undergo re-absorption; should see minimal amounts in urine under normal circumstances)
Electrolytes
Water
Urea
Uric acid
Creatinine
Protein (no large proteins; under normal circumstances there will be some proteins)
8
Q
Describe the process of reabsorption
A
The movement of substances OUT of the renal tubules back INTO the blood capillaries
FILTRATE → BLOOD
9
Q
Purpose of Reabsorption
A
Prevents substances needed by the body from being lost in the urine
10
Q
What molecules are reabsorbed by the kidney?
A
Reabsorption of water and solutes including:
NaCl, K+, HCO3-, urea, amino acids, glucose
100% of glucose and amino caids should be reabsorbed
11
Q
Describe glucose reabsorption in diabetics
A
Under normal physiological conditions 100% of glucose should be reabsorped
In diabetics, the amount of glucose in the blood and ultimately filtrate exceeds the capacity to be reabsorped
12
Q
Describe the process of Na+ and H20 reabsorption
A
Water reabsorption occurs through an osmotic gradient
Where Na+ goes, H2O will go with it
13
Q
How much of the filtrate is excreted in the urine?
A
Less than 1% of the filtrate is excreted
14
Q
Describe the process of secretion
A
Substances move OUT of the blood and INTO the tubules where they mix with the water and other wastes and are converted into urine
BLOOD → FILTRATE
15
Q
What substances undergo secretion?
A
Substances secreted include: H+, K+, uric acid, certain drugs
16
Q
How are substances secreted?
A
Active transport mechanism (e.g., P-glycoprotein)
Diffusion across the membranes
17
Q
Where in the kidney does reabsorption occur?
A
Bulk reabsorption, which is not under hormonal control, occurs largely in the proximal tubule.
Regulated reabsorption occurs in the collecting duct
18
Q
Where does secretion occur in the kidney?
A
Proximal Tubule
Regulated Secretion Collecting Duct
19
Q
Describe acid base balance in the body?How is this accomplished by the kidneys?
A
Body maintains pH within a narrow range (7.35-7.45) by regulating H+ concentration
Accomplished through filtration, reabsorption, secretion in kidney
20
Q
What are some mechanisms of H+ concentration regulation in the body?
A
Mechanisms of H+ concentration regulation:
Lungs: alveolar ventilation of carbon dioxide
Kidney: hydrogen ion excretion, bicarbonate reabsorption, phosphate and ammonia buffer systems
21
Q
Kidneys Regulation of acid base balance
A
Kidney is responsible for secreting acids (H+)
Kidney is responsible for reabsorbing bicarbonate (HCO3-)
22
Q
How does the kidney respond to acidosis?
A
In response to excess acid, kidneys reabsorb all filtered bicarbonate and produces new bicarbonate
23
Q
How does the kidney respond to alkalosis?
A
In response to too little acid, kidneys excrete bicarbonate to restore H+ concentration to normal
24
Q
Examples of of specific substance excretion by the kidney
A
Responsible for the excretion of waste products produced from protein metabolism (uric acid) and from muscle contraction (creatinine)
Renal elimination of certain drugs
Removed by filtration and/or secretion
25
Briefly describe the endocrine functions of the kidney
Produces hormones involved in:
Blood pressure control
RBC production
26
What are some key mechanisms of renal blood pressure mechanisms?
Renin-Angiotensin-Aldosterone System (RAAS)
Antidiuretic hormone (ADH)
Atrial natriuretic peptide (ANP)
27
What is the main mechanims by which kidneys control blood pressure?
RAAS System
28
Describe the RAAS system?
Main mechanism by which the kidneys control blood pressure
For filtration to occur, hydrostatic blood pressure must be at a certain value
Renin is released from renal juxtaglomerular cells in response to decreased blood pressure
Indirectly, renin leads to:
Vasoconstriction
Sodium and water retention
29
Draw out the RAAS system?
30
What is the role angiotensin II?
Angiotensin II evokes vasoconstriction of the efferent arteriole, to increase glomerular hydrostatic pressure
31
What other important endogenous compounds maintain blood pressure? How?What do they also promote?
Prostaglandin E2 and I2
Produced by the kidney in response to decreased blood flow
Cause vasodilation, specifically of the afferent arteriole, to increase renal perfusion
Also promote the secretion of renin
32
Describe the relationship between renal function and NSAIDs?
Prostaglandin E2 and I2
Cause vasodilation, specifically of the afferent arteriole, to increase renal perfusion
--> Why NSAIDs decrease kidney function
--> NSAIDS limit the vasodilation leading to less blood flow
33
What is aldosterone? What is its mechanism?What are some other functions?
Secreted by the adrenal cortex in response to Angiotensin II
Primary role is to stimulate tubule reabsorption of sodium
This means sodium (salt) moves OUT of the kidney/renal tubule and INTO the blood/body
Wherever salt goes, water follows --> BP goes up
Indirectly:
Increases potassium excretion
Increases H+ excretion
34
What is antidiuretic hormone (ADH)? Mechanism?
Secreted by the posterior pituitary in response to increased blood sodium levels / low blood volume
Increases water permeability of the collecting ducts, promoting water reabsorption
Means water is going BACK into the BLOOD instead of being peed out
Thus, the kidney excretes a more concentrated urine (antidiuresis)
35
What is atrial naturietic peptide (ANP)?
Stored in the right atrium of the heart
Released in response to increased stretch of the heart muscle
Indicative of fluid overload
Elevated in heart failure
Opposes the actions of RAAS by causing vasodilation and increased renal excretion of sodium (opposite effect of aldosterone)
36
How do the kidneys regulate RBC production?
ERYTHROPOIETIN
Stimulates production of red blood cells (increase oxygen-carrying capacity of the blood)
90% produced in the kidneys by peritubular interstitial cells
Produced by the kidneys in response to decreased blood oxygen levels (anemia, hypoxia, etc.)
Deficient/lack of erythropoeitin production in chronic kidney disease (CKD) leads to anemia
37
What are the metabolic functions of the kidney?
Metabolism of endogenous compounds (e.g., insulin)
Vitamin D activation
Gluconeogenesis
38
Describe the process of vitamin D synthesis in the kidneys?
39
Describe vitamin D activation by the kidneys?
Vitamin D has to be activated by the liver and then the kidney before it can exert its effect
Cholecalciferol → calcidiol → calcitriol
In CKD, vitamin D activation is impaired
Leads to disruption of the calcium-phosphorus-parathyroid hormone balance and renal bone disease
40
Describe the process of gluconeogenesis in the kidney?
To make glucose from amino acids
Most of gluconeogenesis occurs in the liver, but some also occurs in the cortex of the kidney
41
Why do pharmacists check renal function?
Monitoring and early recognition of CKD
--> Monitoring the effect of drugs on slowing progression
--> Predict the time to onset of ESRD
--> Evaluating risk of complications
To adjust doses of medications excreted by the kidneys (renal dose adjustments)
Monitoring nephrotoxic medications
42
What is creatinine?
a by-product of muscle metabolism that is primarily eliminated by glomerular filtration
43
What is serum creatinine?
Concentration of creatinine in the blood
Endogenous substance
A way to measure the filtration rate
When GFR is low, SCr is increased
44
What does MDRD measure?
measures the GFR
45
What does CKD-EPI measure?What is it used for?
Glomerular filtration rate, new improved version of MDRD, more accurate estimates especially when GFR is >60 ml/min
Used for classifying the severity of kidney dx
46
What does the cockcroft-gault equation measure?
Creatinine Clearance; not GFR
47
What does the salazar corcoran measure?
Creatinine Clerance for Obese patients
48
What equation is used for making renal dose adjustments for medications?
Cockcroft-Gault most common measure for renal dose adjustments; increasing popularity to use eGFR for renal dose adjustments (more accurate estimate of someone's true ability to eliminate drugs through the kidneys)
Need to be manually calculating when using Cockcroft-gault
49
T/F: The CKD-EPI equation is used to estimate kidney function in a patient receiving dialysis
False
50
What are some sources of error in GFR estimating using creatinine?
51
What equations are used to calculate stable renal function?
Most patients with stable renal function = CKD-EPI and Cockcroft-Gault equation
--> To calculate CrCl for the purpose of DRUG/DOSE ADJUSTMENT, use COCKROFT-GAULT
--> To calculate eGFR to STAGE CKD, use CKD-EPI
In practice, check the drug monograph to see what equation to use for dose adjustments
52
Are all kidney measurements 100% accurate?
NO KIDNEY MEASUREMENTS are 100% accurate --> all are estimates
53
What is a new major update to the CKD-EPI equation?
Have removed ‘race’ from the equation
Impact: lower eGFR in patients who self-identify as Black race and higher eGFR in patients who self-identify as non-Black race
54
In a new update to the CKD-EPI equation, what is the difference between indexed and non-indexed?
Indexed or Normalized
- Standardized to a BSA of 1.73m2
- Units: mL/min/1.73m2
- Recommended for CKD staging/progression
Non-indexed or Without Normalization
- Adjusted (calculated) according to the patient’s BSA
- Units: mL/min
- Consider for drug dosing (caution in morbidly obese patients, as can lead to overdosing)
55
What is the Bedise Schwartz equation?
Pediatrics GFR
56
An alternative to creatinine for calculation GFR is....
Cystatin C
57
Urea as a test of kidney function
- AKA Blood Urea Nitrogen (BUN) - produced as a break down product of protein
- Filtered by the kidney but is also reabsorbed, therefore measurement underestimates GFR
- Not strictly regarded as a renal function test, but increases in renal impairment
58
What can elevate BUN?
dietary protein (falsely elevated BUN that has nothing to due with kidney function)
GI bleeding(Increased BUN due to ingestion of blood; protein)
hydration status (HIGH urea means LOW water; dehydration) – independent of kidney function
59
Whatis BUN dependent on? BUN and GFR relationship
The production of urea depends on good liver function (liver for conversion piece) and the availability of protein
When GFR decreases, BUN goes up. However a high BUN may be indicative of something else
60
Is protein often lost in the urine?
Normally, no/minimal protein is lost in the urine
61
Anothermarker of kidney damage is.... What is this particularily indicative of?
Persistent ↑ in urine protein is a marker of kidney damage (“proteinuria” = bad) --> More specificially glomerular damage (filter)
62
What does the type of protein lost in the urine depend on?
Type of protein lost in the urine depends on type of kidney damage:
↑ albumin excretion sensitive to kidney damage from diabetes, hypertension, glomerular diseases
↑ excretion of low molecular weight globulins in tubulointerstitial kidney diseases (kidney injury from toxins)
63
What is proteinuria?What proteins does oit measure?
General term for presence of increased amounts of protein in the urine
Nonspecific: Albumin +/or other proteins
64
What is albuminuria?What does it predict?
A small amount of albumin in the urine is normal
↑ levels are an early predictor of glomerular dysfunction (especially diabetic kidney disease)
65
What test can be used to evaluate albuminuria?
Screening test is the urine albumin : creatinine ratio (ACR)
Mostly evaluating for albumin (the standard) rather than measuring proteinuria as a whole
WILL SEE INCREASE HERE (ESPECIALLY IN DIABETES) WITHOUT Decreases IN GFR
66
Albumin Categoreiesin CKD and Values
67
Are increases in proteinuria always associated with kidney dx?What is required here?
Transient increases not associated with kidney dx
NEED A REPEATED TEST IN 3 MONTHS TO SHOW THAT THESE ELEVATIONS ARE CONSISTENT SINCE ONE MEASURE CAN BE HIGH DUE TO A TRANSIENT CAUSE
68
What are some potential causes for transient albuminuria?
Recent Major Exercise
Urinary Tract Infection
Febrile Illness
Decompensated Congestive Heart Failure
Menstruation
Acute Severe Elevation in Blood Glucose
Acute Severe Elevation in Blood Pressure
69
What is urinanalysis?
Urinalysis – ”routine & microscopic” (R&M)
--> Provides info about the physical and chemical composition of urine
70
What does urinalysis measure?
Colour, turbidity
Presence of cells, micro-organisms, “casts,” crystals
--> Granular casts, RBC casts, WBC casts
Urinary eosinophils → interstitial nephritis
pH analysis, specific gravity
Glucose, ketones → indicative of diabetes/DKA
Leukocyte esterase and nitrite → positive in UTIs
71
What is urinanalysisused for?Example?
Narrow down the cause of kidney dx and detect things that may not have been found as they are asymptomatic
RBC’s that are dysmorphic --> As pass through structure of kidneys become disformed
--> If not dismorphic, mor elikely to be in later urinary tract (e.g. bladder)
72
What urinary electrolytes used for?
Used to differentiate causes of AKI
73
Urinanalysis criteria for CKD
74
what are CASTS?
Cylindrical protein structure, assume this shape as formed in the tubules of the kidneys, found in the urine under a microscope
DO not always indicate kidney diseases (e.g. hytaline cast, granular cast in dehydrated healthy people)
WBC, RBC --> ANY CELLS --> pathological condition Should not see cells being filtered
75
Define acute kidney injury (AKI)
A sudden decline in renal function (hours or days) as evidenced by changes in laboratory values (SCr, BUN, and urine)
76
Can the CKD-EPI equation be used to estimate kidney function in someone experiencing an acute kidney injury?How is an AKI diagnosed?
NO
Developped in individuals with stable kidney function, not acutely changing
--> A lag time before serum creatinine rise in AKI
AKI diagnosed based off of urine output and serum creatinine
Urine production decreases with AKI
77
How ca an acute kidney injury be classified?Can urine production always be used to diagnose AKI?
Anuric
less than 50 mL/day urine output
Oliguric
less than 500 mL/day urine output
Non-Oliguric
greater than 500 mL/day urine output
Urine Production decrease ---> Dehydration
Urine Production Increase --> Diuretics
Urine volume can be misleading and not indicative of AKI in all cases
78
What is the RIFLE criteria of an AKI?
79
What is the AKIN criteria of an AKI?
80
In regards to the classification of an AKI, what takes precedence?
Urine output takes precedence in RIFLE and AKIN criteria
81
What do all staging systems depend on?
All staging systems depend on SCr and urine output as the main diagnostic criteria
Associated with the same inherent weaknesses
82
Describe the changes noted in AKI regarding SCr and urine output. Why is this critical? How can we detect changes in SCr?
After development of AKI, may take up to 4 days before an ↑ in SCr is observed
The lag time may significantly delay the diagnosis of AKI and impact outcomes
↓ in urine output emerges earlier in AKI but is a non-specific marker
All criteria based on detecting CHANGE in SCr
Therefore, need to know the patient’s baseline!
83
How does an AKI present sx wise?
Most patients with AKI are asymptomatic
Diagnosed based on laboratory data (↑SCr, BUN)
~50% are oliguric
Patients may present with:
Signs and symptoms of dehydration (pre-renal)
Malaise, anorexia, nausea, vomiting, pruritis (uremia)
Severe abdominal or flank pain (kidney stone?)
Decreased force of urine stream (obstruction)
Cola-coloured urine (blood?)
Excessive foaming of urine (protein in urine)
Sudden weight gain, edema
84
What are some risk factors for an AKI?
Anything that ↓ blood flow to the kidneys
Pre-existing renal dysfunction (acute-on-chronic)
85
Drugs account for what percentage of AKI's?
DRUGS account for ~ 20% AKI cases!
86
How are the causes of an AKI classfied?
Most commonly the cause is classified based on the location of the problem:
1) Pre-renal:
blood supply (including renal artery)
2) Intra-renal or Intrinsic:
tubules, glomerulus, interstitium, vasculature
3) Post-renal:
collecting tubule, ureter, bladder, urethra
87
What is the most common cause of an AKI (classfication wise)?
Pre-renal - Most common cause of AKI (~60% cases)
88
What is another name for pre-renal AKI's?
prerenal azotemia
89
What is the reason for the development of a pre-renal AKI?
Kidney not getting adequate blood supply to filter the blood (“hypo-perfusion”)
Kidneys themselves are healthy
Kidneys can modify the rate of filtration based of vasoconstriction or dilation of efferent/afferent
90
In a pre-renal AKI, decreased kidney perfusion may be from:
Intravascular volume depletion (e.g., hemorrhage, dehydration, burns, diuretic therapy)
Decreased effective circulating volume (e.g., HF, cirrhosis)
Hypotension (e.g., vasodilating medications, septic shock)
Decreased glomerular filtration pressure (ACEi/ARBs + NSAIDs)
91
How much of AKI's are Intrinsic AKI's?
25-35% AKI cases
92
An intrinsic AKI is a result of.....due to....
Results from direct damage to the kidney
Due to ischemia, toxins, or disease
93
What are the main types of an intrinsic AKI?
Acute tubular necrosis (tubule damage) – damage tubular endothelial cells – e.g., endogenous (myoglobin - Rhabomyolysis) or exogenous (aminoglycosides) toxins, ischemia
Acute interstitial nephritis- injury to interstitium around the tubules e.g., idiopathic hypersensitivity immune reaction to drugs (NSAIDs, penicillin), infection
Acute glomerulonephritis – glomerulus injury e.g., post-strep antigen-antibody complexes
Vascular kidney injury – e.g., renal artery stenosis, HTN
94
Post-renal AKI's account for how many AKI cases?
< 5% of all cases
Least common AKI
95
What is a post-renal AKI? Where?
Obstruction to urinary flow anywhere in the urinary tract:
Urethral obstruction
Ureter obstruction (Would need both ureters)
Bladder neck obstruction
96
What are some causes of a post-renal AKI?
Nephrolithiasis (kidney stones)
Prostate enlargement
Cervical cancer tumors
Drugs that crystallize (sulfonamides, acyclovir, MTX)
97
Whatis the process for diagnosing an AKI?
History
Laboratory Data
Serum Creatinine
Urinary Sodium Concentration
Fractional Excretion of Na+ (FeNa)
Urinanalysis
Renal Ultrasound
Kidney Biopsy
98
In a history for the diagnosis of an AKI, considerations are....
(so many potential causes, what drugs, sick, how long drugs, dehydrated, etc.)
99
In the laboratory data for the diagnosis of an AKI, one would expect.....
↑SCr,↑BUN, acidosis, hyperkalemia
100
Serum Creatinine consideration for the diagnosis of an AKI
Changes in SCr will lag behind the decrease in kidney function due to slow accumulation, increased tubular secretion, and increased extra-renal clearance
101
What is the difference between urinary sodium concentration and FENa?
The fractional excretion of sodium (FENa) is the percentage of the sodium filtered by the kidney which is excreted in the urine. It is measured in terms of plasma and urine sodium, rather than by the interpretation of urinary sodium concentration alone, as urinary sodium concentrations can vary with water reabsorption.
102
What is FENa? Consequences?
FENa (Fractional Excretion of Sodium) = % sodium filtered by the kidneys that is excreted in urine
↓ with pre-renal AKI
↑ with tubular damage- intrinsic
Decrease in pre-renal AKI because RAAS system activated, the reabsorption of Na+ to increase H2O reabsorption to increase blood pressure to maintain perfusion --> LESS NA+ excreted
Tubular damage because reabsorption process impaired
103
Is FENa a specific measure for kidney damage? Why or why not? Example?
Not specific to kidney damage – can be affected by other factors (e.g. furosemide, blocks Na+ in loop of henle, may increase NA+ levels requiring interpretation)
104
Urinanalysis Findings for the Diagnosis of an AKI
Cellular debris (“casts”) → seen with acute tubular necrosis
Hematuria, proteinuria → indicate glomerular injury
↑ WBC → UTI/pyelonephritis
Pyuria, urinary eosinophils → acute interstitial nephritis
Crystals → post-renal AKI (can also see hematuria with kidney stones)
Pre-renal AKI --> generally few WBCs, casts, etc., but ↓ FENa (All due with hemodynamic as kidney itself is healthy)
105
Are kidney biopsies common?
Invasive, only used if necessary
106
What are the goals of therapy for an AKI?
Prevent further renal injury (detect and remove the cause)
Minimize extra-renal complications
Facilitate recovery of renal function back to baseline
107
Describe the treatment of an AKI?
Treatment is largely supportive
108
Treatment of pre-renal failure
Hydration with IV fluids (e.g., isotonic sodium chloride) if hypovolemic - stop diuretics
BP support with vasopressors (dopamine, norepinephrine, vasopressin as applicable)
Sepsis, septic shock, vasomotor shock
Fluid removal in volume overload states (e.g., heart failure) with diuretics
Stop (or “hold”) drugs that impair kidney function/urine flow (e.g., NSAIDs)
109
Treatment of intrinsic renal failure
Discontinue offending agent
Manage underlying autoimmune disease
110
Treatment of post-renal failure
Catheter to restore urine flow
Identify and remove obstruction
Adequate hydration when giving drugs with potential to crystallize
111
What is hyperkalemia?How is K+ managed? Kidneys role?
Serum K+ levels maintained in a narrow range (3.5-5mmol/L) by several mechanisms (e.g., insulin, aldosterone, epinephrine)
The kidney is the primary route of K+ elimination
↑ serum K+ seen with AKI and CKD
112
Mild-moderate hyperkalmeia is defined as..... SX?
Mild-Moderate (K+ 5.1-7mmol/L)
weakness, confusion, muscle twitches, ECG changes (peaked T-waves)
113
Severe hyperkalemia is defined as.... Sx?
Severe (K+ > 7mmol/L)
ECG changes like widened QRS complex, small amplitude P waves, sine waves → heart block, ventricular tachycardia, death CAN HAPPEN FAST
114
What is considered a high K+ level? Why is this bad?
Can cause sudden arrythmias and death to occur
- Over 5 mmol/L is considered high
115
Treatment of Mild Hyperkalemia
May not require therapy or can use Kayexalate® (sodium polystyrene sulfonate); delayed onset of effect (~1 hour)
--> 15-60g po BID-QID until K+ concentration normalizes
Furosemide (IV) administration to increase urinary excretion
116
MOA of Kayexalate
Cation exchange resin passe through he GI tract and exchanges K+ for Na+ ions Passes out into the stool (K+)
117
Monitoring of Furosemide
Furosemide Monitor for hypokalameia, loop diuretics
Eliminate potassium through the kidney
need functional kidneys for furosemide to have an effect
118
Tx of Severe Hyperkalemia
If severe: (K+ >7 mmol/L or ECG changes) → Medical emergency!
1. Calcium gluconate to stabilize myocardium
To drive K+ into cells (combo of these may be used):
- Rapid-acting/Regular insulin +/- glucose (depending on BG levels)
- Sodium bicarbonate IV infusion (if metabolic acidosis present)
- Salbutamol via nebulizer (if pulmonary congestion)
3. Kayexalate → eliminate excess K+ from the body (slower onset)
If refractory → dialysis
119
Tx of Severe Hyperkalemia Mechanims Simple
Move from the bloodstream into the tissues; not necessarily trying to get out of the body
120
Tx of Fluid overload in an AKI
Leads to pulmonary congestion and edema
Diuretics (furosemide +/- metolazone)
121
Tx of metabolic acidosis in an AKI
Treat with sodium bicarbonate IV
122
Uremia AKI Consequences
May cause nausea, vomiting, anorexia
If severe can progress to mental status changes, coma
123
When to dialyze in an AKI?
More likely to start dialysis in AKI with hyperkalemia and metabolic acidosis
CKD is mainly uremia
