L5-6: Renal Flashcards
Physiological functions of the kidneys
Endocrine functions
Control of solutes and fluids
BP control
Acid/Base balance
ADME
Metabolic waste excretion
When something goes wrong with the kidney - BIG problem - not easy to manage
Main function of the kidney
Filtration
Continuously working - if damaged - management difficult
Avg kidney has how many nephrons
1 million - decreases with age
Bowman’s Capsule
Osmatic pressure filtering (BP makes a big deal)
How much pressure is present DIRECTLY AFFECTS how much filtering happens in Bowman’s capsule
All parts are surrounding the _ and therefore do heavy function around it
Glomerulus
Glomerular Filtration depends on
GFR
Size of drug
Extent of plasma protein binding: only unbound is filtered
Renal excretion of unchanged drug is a major route of elimination for 25-30% of drugs
Main site of drug secretion and drug reabsorption
Secretion: Proximal tubule
Reabsorption: Distal Tubule
ONLY two places drug can go in and out
Review of Renal Anatomy and Reabsorption
Bowman’s Capsule: 100% filtrate produced
Proximal Tubule: 80% filtrate reabsorbed Active and Passive absorption
Loop of Henle 6% filtrate reabsorbed H2O and salt conservation
Distal Tubule 9% Filtrate reabsorbed Variable reabsorption active secretion
Collecting Tubule 4% Filtrate reabsorbed Variable salt and H2O reabsorption
What % of filtrate (including water) is reabsorbed in proximal tubule
80% most H2O and solutes reabsorbed
Concentrate waste
What is the percent of filtrate produced volume?
1%
Filtrate is VERY strong
Water ALWAYS follows sodium
Cardiac output
6,000mL/min
Renal blood flow rate (18%CO)
1,100mL/min
Renal Plasma flow rate (60% RBF)
660mL/min
Effective renal plasma Flow rate (90% RPF)
600ml/min
Filtration fraction (18% ERPF)
110mL/min
Urine output
1mL/min
Reabsorbed Filtrate (FF-UO)
109mL/min
Cardiac output cont
6,000mL/min
10% (600) is plasma
-Very small
Less than half is our urine output
Normal urine frequency: 2-4 hours
More frequent if diuretics used = less patient adherence
Anatomical Solute and water flux in nephron
ALL organic things are reabsorbed from proximal
Blood in urine = something wrong with proximal = reabsorption impaired
Bicarbonate role
Goes with proton (acid/base)
All water transportation is controlled
Potassium goes (with/against) sodium
Against
Collecting duct
Urea and Water excreted
K, H, NH3 reuptake
Glomerulus
Function: Formation of glomerular filtrate
Water permeability: Extremely high
Primary Transporters and drug targets at apical membrane: None
Diuretic with major action: None
Proximal convoluted tubule (PCT)
Function: Reabsorption of 65% of filtered Na+/K+/Ca+ and Mg2+; 85% of NaHCO3, and nearly 100% of glucose and amino acids, isosmotic reabsorption of water
Water permeability: very high
Primary Transporters and drug targets at apical membrane: Na/H1, carbonic anhydrase, Na/glucose cotransporter 2(SGLT2)
Diuretic with major action:
Carbonic anhydrase inhibitors; adenosine antagonists (under investigation)
Proximal Tubule, straight segments
Function: secretion and reabsorption of organic acids and bases, including uric acid and most diuretics
Water permeability: very high
Primary Transporters and drug targets at apical membrane: Acid (eg. uric acid) and base transporters)
Diuretic with major action:
None
Thin descending limb of Henle’s loop
Function: Passive reabsorption of water
Water permeability: high
Primary Transporters and drug targets at apical membrane: Aquaporins
Diuretic with major action:
None
Thick ascending limb of Henle’s loop (TAL)
Function:
Active reabsorption of 15-25% of filtered Na+/K+/Cl-; secondary reabsorption of Ca2+ and Mg2+
Water permeability: Very low
Primary Transporters and drug targets at apical membrane: Na/K/2Cl (NKCC2)
Diuretic with major action:
Loop diuretics
Distal Convoluted tubule (DCT)
Function: Active reabsorption of 4-8% of filtered Na+ and Cl-; Ca2+ reabsorption under PTH control
Water permeability: Very low
Primary Transporters and drug targets at apical membrane:
Na/Cl (NCC)
Diuretic with major action:
Thiazides
Medullary Collecting duct
Function: Water reabsorption under vasopressin control
Water permeability: variable
Primary Transporters and drug targets at apical membrane:
Aquaporins
Diuretic with major action:
Vasopressin antagonists
Cortical Collecting Tubule (CCT)
Function:
Na+ reabsorption (2-5%) coupled to K+ and H+ secretion
Water permeability: variable
Primary Transporters and drug targets at apical membrane: Na channels (ENaC), K channels, H+ transporter, aquaporins
Diuretic with major action:
K+ sparing diuretics: Adenosine antagonists
Measures of Function
Serum Creatinine
-Predominantly removed by filtration
-Increase = bad
BUN
-Measure of waste from liver breakdown of AAs
-Increase = BAD
CrCl
-Useful for predicting secretion and drug clearance
GFR
-measure of nephron function
Markers of damage
Urine abnormalities
(Protein, RBC suggestive of membrane malfunctions)
Imaging abnormalities (MRI/CT scans)
Kidney function declines with age due to
Decline in nephrons
Decreased by HALF
Higher pressure - ones that are there will not last as long
Compensatory Response to Renal Injury
Renal injury
Decrease in number of nephrons
Compensatory increase in size and function of remaining nephrons
Glomerular and tubular lesions
Loss of nephrons greater than compensatory capacity
Progressive decrease in GFR
Azotemia
Uremic Syndrome
DEATH
Sources of Kidney Injury/Failure
HTN and Diabetes account for >60% of renal failure cases in the US!!
Pts often realize too late
Glomerulonephritis
-Kidney injury/disease
Cystic Kidney
AKI Death rate
300,00 people US annually
-Death rate more than breast cancer, prostate cancer, heart failure AND diabetes combined
Pathophysiology of Acute Kidney Failure
An increase in Scr >0.3mg/dL *26.5mmol/L) within 48 hr
OR
Increase in SCr >50% (>1.5 times baseline) which is known or presumed to have occurred in last 7 days
OR
A reduction in urine output (oliguria of <0.5 mL/kg/h for 6 hours)
Major causes of AKI: Prerenal
Hypovolemia
Decreased Cardiac Output
Decreased effective circulating volume
-Congestive Heart failure
-Liver failure
Impaired renal autoregulation
-NSAIDs
-ACE-I/ARB
-Cyclosporine
Major causes of AKI: Intrinsic (Intrarenal)
Glomerular
-Acute glomerulonephritis
Tubules and interstitium
-Ischemia
-Sepsis/infection
Nephrotoxins
Vascular
-Vasculitis
-Malignant HTN
-TTP-HUS
Major causes of AKI: Postrenal
Bladder outlet obstruction
-Bilateral pelvoureteral obstruction (uinlateral obstruction of a solitary functioning kidney)
Intrarenal mechanisms for autoregulation of GFR under decreased perfusion pressure and reduction of GFR by drugs
Normal Glomerular capillary pressure is maintained by afferent vasodilation, and efferent vasoconstriction
Reduced perfusion pressure with an NSAID - Loss of vasodilatory = prostaglandins increases afferent resistance
Drops pressure, causes GFR to decrease
**reduced perfusion pressure with an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin receptor blocker (ARB)
Loss of Angiotensin II action reduces efferent resistance, this causes the glomerular capillary pressure to drop below normal values and the GFR to decrease
Primary causes of AKI
Sepsis
Ischemia
Nephrotoxins
Obstruction sites causing AKI
Kidney
-Stones, blood clots, external compression, tumor, retroperitoneal fibrosis
Bladder
-Prostatic enlargement, blood clots, cancer
Urethra
-Strictures
-Obstructed Foley Catheter
Pathophysiology of CHRONIC kidney disease
THREE MAIN CAUSES
-Increased glomerular capillary pressure
-Causes damage
Proteinuria
-Filtration damage = kidney damage
Glomerulosclerosis
Key abnormalities that give rise to CKD-Mineral Bone disorder
Potassium (Impaired phosphate excretion)
Vitamin D conversion
(1,25-Dihydroxyvitamin D3)
Vitamin D metabolism
Production of active Vitamin D requires conversion of 7-dehydrocholesterol to cholecalciferol (Vitamin D3) by sunlight, followed by the first hydroxylation step in the liver to form 25-hydroxyvitamin D3, or 25(OH)D3, and the final conversion step in the kidney to form 1,25-dihydroxyvitamin D3 or Calcitriol.
Managing CDK patients requires dealing with Ca homeostasis
ONLY the liver and Kidney carry calcitriol - without proper function = cannot have Vitamin D
Uremia
Uremic illness is due largely to the accumulation of organic waste products, not all identified as yet, that are normally cleared by the kidneys
Uremic solutes
-Signs and symptoms
-Can be termina l
-Neuro, muscular, endocrine, metabolic
Specific Nephropathies
Nephritic Syndromes
Nephrotic Syndrome
Cystic Disease of the Kidney
Nephrolithiasis
Contrast-induced Nephropathy
Nephritic vs Nephrotic
Nephritic
I = inflammation
Blood in urea
Nephrotic
o = pOdOcyte damage
Once structure/barrier damaged - protein can easily get through
Typical Features of Nephrotic syndrome
Insidious Onset
LARGE edema - proteins LEAKING
Normal BP
Normal jugular venous pressure
**LARGE proteinuria **
Hematuria may/may not occur
RBC casts - absent
Serum Albumin - LOW
Typical features of nephritic syndrome
Abrupt onset
Some Edema
BP raised
Jugular venous pressure raised
Proteinuria - present
Hematuria - SIGNIFICANT
RBC casts - PRESENT
Serum albumin - normal/slightly reduced (wasted)
Glomerulonephritis
Inflammation of Glomeruli
acute and chronic forms
Presents with proteinuria and or hematuria
Primary causes include inheritable trait (Alport Syndrome)
Secondary causes: infections DRUGS, and autoimmune disorders (vasculitis, Lupus
Pathogenesis of Glomerular Diseases (Pathogenesis = Immune reaction)
- Antibody associated injury
- Cell mediated immune
- Other mechanisms of Glomerular Injury
Pyelonephritis
Inflammation of kidney tissue
-Usually bacterial infection
-ANNA
Acute and chronic forms
Presents flank pain with painful urination
Causes are bacteria from blood or urinary tract
White cells in urine
May lead to sepsis
Interstitial Nephritis
Primary injury to renal tubules and interstitium
Undetected until causes significant decrease in renal function
Causes:
DRUGS 70-75% - mostly antibiotics
Infection 4-10%
Autoimmune (10-20%) SLE, sarcoidosis
Drugs associated with interstitial nephritis
Antibiotics
Penicillin
Cephalosporins
Sulfonamides
Diuretics
-Thiazides
-Furosemide
Anticonvulsants
-Phenytoin
-Carbamazepine
-Phenobarbital
Analgesics
-NSAIDs
Other
-Allopurinol
-Cimetidine
Cystic Diseases of the Kidney: Simple Cysts
Simple cysts
-Most common form of cystic renal disease
-Should be distinguished from kidney tumors
Cystic Diseases of the Kidney - Autosomal Dominant (Polycystic Kidney Disease (Adult) (APKD)
Definition: multiple expanding cyts of both kidneys that ultimately destroy the intervening parenchyma
Pathogenesis of Autosomal adult PKD
-Inherited mutation of PKD1 or pKD2
Abnormal cysts formation in both kidneys
Ultimately destroy the intervening parenchyma
HTN and UTI - ultimately fatal - renal transplant necessary
Cystic Diseases of the Kidney Autosomal Recessive (childhood) PKD
Pathogenesis:
-Autosomal recessive inheritance
-Mutation in PKHD1 - fibrocystin (polyductin)
Clinical features
-Serious manifestations are usually present at birth
-Young infants die quick
-Patients who survive infancy develop cirrhosis
Nephrolithiasis - Kidney Stones
Lifetime prevalence - 10% men, 5% women
Arises from a supersaturation of solutes (Calcium)
Hematuria
Nephrolithiasis (Kidney stones) composition and treatment
70-80% from calcium
-Majority of kidney stones - cannot do anything, has to pass
Change diet
-Hydration
Main cause: acute dehydration - precipitation
Surgery/procedure - rare
Primary treatment
-Analgesis
Hydration
-Lithotripsy
-Surgical Removal
Prevention
-Diet (hydration; eliminate Ca supplements)
Diuretics
Contrast-Associated Nephropathy
25% increase in SCr within 72 of contrast media admin
CIN causes 1/3 hospital acquired AKI
Affects 1-2% of the US population
Hydration for prevention
Avoid concurrent nephrotoxins
Recent work suggests frequency may be overestimated and most methods to reduce incidence have proven to be ineffective
