Renal Module I Flashcards
What space are the kidneys located?
Retroperitoneal
Which kidney is slightly lower?
right kidney (due to liver)
What are the kidneys protected by?
Posterior wall muscles and ribs
Approximately what are the measurements of the kidneys?
4-5 inches long, 2 inches tall
What arteries supply kidneys?
R/L renal arteries
How many liters of blood do the kidneys receive per minute? This accounts for how much of the cardiac input?
~1-1.25 L/min (20-25% cardiac output)
What is the dense connective tissue that surrounds the kidneys?
Renal capsule (fibrous capsule)
What is the layer of fat that provides shock absorption in the kidneys?
Renal fat pad
What is the connective tissue layer that surrounds the renal pad?
Renal fascia
What is a common symptom of many urinary tract diseases?
Flank pain/CVA tenderness
What causes flank pain?
Distention of the renal capsule, renal pelvis, and ureter
What causes “higher” flank patterns when compared to ureter pathology?
Kidney pathology
Severity of flank pain is directly related to what? What is it nor directly related to?
Directly related to speed of onset (but not degree of distention)
Ex. small kidney stone lodged in the ureter causes more pain than a slow growing, large tumor that distends the ureter
What is the outer region of the kidney that contains the nephrons?
Renal cortex
What is the inner region of the kidney that consists of renal columns and pyramids?
Renal medulla
What are the spaces located between each renal pyramid that contain nephrons?
Renal columns
What are the triangular shaped spaces that contain nephritic tubules (loop of Henle) and collecting ducts?
Renal pyramids
Where do the renal pyramids descend to?
The renal papilla (apex of the pyramids)
What is the urine pathway?
Flows from: Collecting ducts in the renal papilla (apex) -> minor calyce-> major calyce -> renal pelvis -> ureter
-> bladder
What do the calyces, renal pelvis, and ureters contain to facilitate the flow of urine into the bladder?
Smooth muscle
What is a ureteral stent (ureteric stent)?
Thin tube inserted into ureter to prevent or treat urine obstruction
Indications for a ureteral stent?
-Bilateral ureteral obstruction
-Obstruction of solitary functioning kidney
-Ureteric injury
-Post treatment of urolithiasis in pts w/ solitary kidney
When is pre-surgical ureteral stenting used?
Prophylactically in case of injury to ureter during surgery
What is considered the functional unit of the kidney?
Nephrons
How many nephrons per kidney?
1.2 million
What is the role of nephrons?
Formation of urine
Structures of nephrons?
-Renal corpuscle
-Glomerulus
-Bowman’s capsule/space
-Proximal convoluted tubule
-Loop of Henle
-Distal convoluted tubule
-Collecting duct
What are the two types of nephrons?
Cortical and juxtamedullary
What percentage of nephrons are cortical?
85%
Cortical nephrons extend partially into what structure?
Medulla
What are cortical nephrons responsible for?
Filtration, absorption, secretion, and excretion
What percentage of nephrons are juxtamedullary?
15%
Juxtamedullary nephrons extend deep into what structure?
Medulla
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
What are juxtamedullary nephrons responsible for?
Urine concentration, filtration, absorption, secretion, and excretion
“Capillaries from renal circulation that extend into Bowman’s capsule/space” describes what structure?
Glomerulus
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
What is Bowman’s capsule?
The first section of the nephron (entrance point)
The renal corpuscle is the site of what?
Filtration
Blood enters the glomerulus through what?
Afferent arteriole
Blood is filtered where?
Glomerulus
Plasma is filtered through what structure before entering Bowman’s capsule? What is blood known as when it reaches Bowman’s capsule?
Passes through glomerular filtration membrane,
Blood is known as filtrate
What happens to blood that is not filtered by the renal corpuscle?
Exits glomerulus through efferent arteriole
What serves as the “filter for the nephron”?
Glomerular filtration membrane
What is the glomerular filtration membrane formed by?
Walls of both the glomerular capillary and Bowman’s capsule
What are the three layers of the glomerular filtration membrane?
-Fenestrated endothelium of the capillary
-Glomerular basement membrane (GBM) of the capillary
-Podocytes formed by the epithelium of Bowman’s capsule
What does the term mesangium (in the context of glomerular mesangial cells) refer to?
Space between the glomerular capillaries
Where are the glomerular mesangial cells located?
Centrally in space between glomerular capillaries
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
What do glomerular mesangial cells consist of?
Matrix of smooth muscle cells and phagocytic cells
Function of glomerular mesangial cells?
Contraction/relaxation to regulate filtration by altering surface area of glomerular filtration membrane & phagocytic removal of macromolecules
What is the proximal convoluted tubule (PCT) a continuation of?
Bowman’s capsule
What is the PCT?
Single layer of simple cuboidal cells w/ microvilli that line the lumen wall
What do the microvilli of the PCT provide?
Large surface area for reabsorption/secretion (form a brush border similar to small intestine)
Function of the PCT?
Reabsorb most of the filtrate (60-95%) & secrete some drugs and meds (antibiotics, ACE-I, many other metabolic byproducts)
What is the loop of Henle formed by?
Descending limb and ascending limb-and its sub region known as the thick ascending limb (TAL)
Where is the juxtaglomerular apparatus (JGA) located?
Where the distal convoluted tubule passes by the glomerular arterioles
What is the role of the juxtaglomerular apparatus (JGA)?
Regulation of renal blood flow, glomerular filtration, and renin secretion
What kind of cells are in the juxtaglomerular apparatus (JGA)?
juxtaglomerular cells, mesangial cells, macula densa
What are juxtaglomerular cells in the JGA?
granular cells located adjacent to the afferent glomerular arteriole
What are mesangial cells in the JGA?
Continuation of mesangial cells from glomerulus
What are the macula densa of the JGA?
Specialized receptor cells located in the distal convoluted tubule that monitor sodium-chloride concentration of filtrate flowing through the nephron
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
What are the borders of the distal convoluted tubule?
Begin at macula densa, end at connection to collecting duct
What makes up the epithelium of the distal convoluted tubule?
Simple cuboidal cells w/ fewer microvilli than PCT cells
How is the distal convoluted tubule divided?
Functionally- into early DCT and late DCT
What is the function of the early DCT?
Continues to dilute filtrate, reabsorbs sodium
What is the function of the late DCT?
Begins to concentrate fluid as it enters the collecting duct
Numerous collecting ducts are found where?
In each renal pyramid
Each collecting duct will descend to the _____ and drain into the _____?
descend to renal papilla, drain into minor callyces
How many nephrons drain into each collecting duct?
Several
As the collecting ducts descend they merge to form about 30 ducts that open where?
Renal papilla
Epithelium of the collecting duct? What is the epithelium’s important role?
Simple squamous epithelium line the collecting ducts
Role: final fine tuning of urine concentration/water reabsorption, and urine dilution
Which filtration layer is a capillary wall with microscopic openings?
Fenestrated endothelium of the capillary
Openings in the fenestrated endothelium of the capillary are about how big?
60-80 nm
How large is a RBC?
8,000 nm
How large is a WBC?
8,000-15,000 nm
How large are most plasma proteins?
> or = 60 nm
The fenestrated endothelium layer of the capillary blocks what from passing?
Blood cells and some proteins (too large to fit through openings), but allows all other material to pass (small enough to fit through openings)
The fenestrated endothelium of the capillary has what charge? What lipoprotein lines the endothelium?
negative
lipoprotein glycocalyx is negatively charged- small molecules that can fit through the openings may be repelled/prevented from passing (charge acts as a push back to acid in filtration)
Which filtration layer is a thin gel layer of collagen and other proteins (proteogycans, glycoproteins) that sits between the glomerular capillary wall and podocytes?
Glomerular basement membrane (GBM)
What are the three sub-layers of the GBM?
-inner/outer layers with negative charge
-middle layer made of collagen matrix
-spaces between collagen matrix creates ~10nm “pores”
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
How does the GBM potentially filter molecules?
Pore size (blocks molecules >7-10nm)
Polarity (negative layer charge repels smaller molecules that are negatively charged)
Epithelium of bowman’s capsule?
Podocytes w/ “foot-like” projections (that are negatively charged)
The foot like projections of podocytes wrap around what structure? What does this create?
Wrap around capillaries, creates matrix of ~40nm filtration slits/openings (also contain slit diaphragm/SD)
What is a slit diaphragm?
A layer formed by complex arrangement of micro-proteins (critical role in final ultrafiltration of plasma)
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
What is proteinuria?
Damage to the podocytes/slit diaphragms allowing for excess albumin & other plasma proteins to flow into the nephron
How do plasma proteins circulate?
In negatively charged lipoprotein packages
Plasma proteins?
Bilirubin, hemoglobin, albumin, immunoglobulins, fibrinogen
Can most plasma proteins and lipoprotein molecules pass through fenestrated openings (60-80nm) and the GBM (~10nm)?
No, most are too large to pass
Which plasma proteins are able to pass through openings/filtration?
Albumin (due to shape), and some other smaller proteins
Some albumin passes through the filtration membranes to the nephron while the rest is repelled by what?
Negative polarity
Why cant unconjugated bilirubin pass through the kidney if it is 1nm in size/able to fit?
Unconjugated bilirubin is not soluble in water, and cannot be renally excreted (needs to be bound to albumin to be soluble)
How do fats circulate?
Attached to protein carrier as negatively charged protein packages
Lipoprotein sizes?
HDL ~ 8-13 nm
LDL ~ 18-23 nm
VLDL ~ 30-80 nm
chylomicrons ~ 75-1200 nm
Why are smaller lipoproteins repelled by the GBM & filtration slits?
negative charge
Pathology of what kidney structures will result in blood cells, proteins, or other substances to pass into urine?
-Glomerular capillary
-GBM
-Podocytes
Clinical meaning of proteinuria?
Excess level of proteins in urine, “foamy pee”
(damage to podocytes lets excess albumin pass into nephron)
Clinical meaning of hematuria? What leads to hematuria?
Any condition where blood is found in the urine
–> inflammatory pathology/damage to capillary wall or GBM will lead to hematuria
Are nephrotic and nephritic syndromes a specific pathology/disease?
No, generally represent lab findings associated with different renal pathologies/diseases
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
What does nephritic syndrome refer to?
Renal pathology that leads to hematuria as the primary finding
*inflammation/damage to GBM/capillary wall
What does nephrotic syndrome refer to?
Renal pathology that leads to proteinuria (albumin) as the primary finding
*damage to podocytes
Clinical findings with nephrotic syndrome?
-Proteinuria >3 g/d (protein/albumin in urine is diagnostic)
-Hypoalbuminemia (low plasma albumin due to renal loss), edema as a result of altered albumin levels in the blood
-Lipiduria: hyperlipidemia leads to lipids in the urine
Clinical findings with nephritic syndrome?
-Hematuria (microscopic or gross)
-Red blood cell casts (tiny particles of RBCs found w/ microscope)
-Proteinuria (mild to moderate: 1-3 g/d)
-Oliguria: reduced urine production
What is minimal change disease (MCD)?
Damage to podocytes/foot projections by “effacement” or “fusion” that is difficult to see on light microscopy due to minimal changes
*aka podocyte foot processes disease
can be primary/idiopathic or have secondary causes
Minimal change disease (MCD) is associated with what?
Nephrotic syndrome
What is focal segmental glomerulosclerosis (FSGS)?
Segments of sclerosis in the glomeruli that can display alterations to the mesangial cells and/or loss (“effacement”) of podocyte foot processes
Can have primary or secondary causes
Segmental glomerulosclerosis (FSGS) is associated with what?
Nephrotic syndrome
What is Mesangiocapillary glomerulonephritis (MCGN) aka membranoproliferative GN (MPGN)?
Thickening of the mesangial matrix and glomerular capillary walls due to immune complex deposits and/or compliment factors —> all leading to abnormal GBM formation
Mesangiocapillary glomerulonephritis (MCGN) is related to what?
Both nephrotic and nephritic syndrome
What is anti-GBM disease (Goodpasture’s disease)?
Rare autoimmune disorder that affects kidneys and lungs
–> attacks glomeruli capillaries (&alveolar capillaries), damaging GBM
**Can be fatal if not treated
Anti-GBM (Goodpasture’s disease) is associated with what?
Nephritic syndrome
Blood flows from the descending aorta to which structures of the kidneys?
R/L renal arteries
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
From the R/L renal arteries, multiple branches eventually bring the blood into what?
Afferent glomerular arterioles of the nephrons
Blood is filtered where in the nephrons?
Glomerular capillary beds
After being filtered in the glomerular capillary beds, blood flows out via what?
The efferent glomerular arteriole and enters the peritubular capillaries & vasa recta
From the peritubular capillaries and vasa recta, blood flows where?
Into venous return
What is the role of the afferent arteriole?
Regulates blood entering glomerular capillary bed: constriction or dilation alters filtration
What is the role of the efferent arteriole?
Regulates blood leaving glomerular capillary bed: constriction or dilation alters filtration
Renal circulation pressure of the glomerular capillaries?
Relatively high to encourage filtration, ideally ~ 55 mmHg
*afferent&efferent arterioles regulate ideal glomerular capillary pressure
Renal circulation pressure of peritubular capillaries?
~8 mmHg to allow reabsorption & secretion along tubules of the nephron
Renal circulation pressure of vasa recta? What does vasa recta surround?
~8 mmHg to allow reabsorption & secretion
-Surround loop of Henle in the juxtamedullary nephrons
Renal circulation pressure of venous return?
As blood leaves kidney: ~4 mmHg (typical of IVC pressures)
What is renal blood flow (RBF)?
Volume of blood that flows through the glomerular capillaries of both kidneys per minute
Average RBF?
1.0-1.2 L/min
At rest, what percentage of cardiac output flows into the kidney?
20-25%
What is renal plasma flow (RPF)?
Volume of plasma that flows through glomerular capillaries of both kidneys per minute
Average RPF?
600-700 mL/min
How to calculate RPF?
RPF = RBF (1- hematocrit)
What is glomerular filtration rate (GFR)?
Volume of plasma filtered into Bowman’s capsule per minute
What determines GFR?
Net filtration pressure in the glomerulus
What is net filtration pressure (NFP)?
Net sum of 3 types of pressures acting between the glomerular capillary and Bowman’s space
NFP of healthy adult?
~10 mmHg “pushing into” Bowman’s capsule
Which three pressures form NFP?
-Hydrostatic pressure of glomerular capillary (~55 mmHg pushing into Bowman’s capsule)
-Hydrostatic pressure of glomerular capillary (~15 mmHg pushing into Bowman’s capsule)
-Osmotic pressure of glomerular blood (~30 mmHg pulling back into glomerular capillary)
What is filtration fraction (FF)?
% of renal plasma flow that filters into Bowman’s capsule
Average FF?
20-25%
How to calculate filtration fraction (FF)?
GFR/renal plasma flow
Average GFR? What may cause average GFR to vary?
120 mL/min
Varies w? age, sex, size
What is the gold standard test for measuring GFR? Is it ideal for clinical practice?
Insulin clearance,
not ideal for clinical practice
What is insulin clearance testing?
Infusion of insulin and measure amount of insulin in urine
Why is insulin an ideal marker for GFR?
It is freely filtered by glomerulus and not secreted or reabsorbed in the tubules
Is creatinine easily filtered by the glomerulus?
Yes
How does the urine creatinine test overestimate actual GFR?
Creatinine is also secreted into the proximal tubule, which overestimates amount filtered by the glomerulus
What is a creatinine clearance (CrCl) test?
24 hour urine sample to measure amount of creatinine in urine, blood draw to measure amount of creatinine in the blood
How does CrCl estimate GFR?
Comparing amount of creatinine in urine w/ amount of creatinine in serum
Why is CrCl not routinely used in clinical practice?
Challenge of 24 hour collection
What is estimated cretinine clearance rate (eCCR) testing?
Blood draw to meaure amount of creatinine in blood
How does eCCR estimate GFR?
By calculating creatinine clearance using serum creatinine levels & other factors (age, sex, size)
What needs to be maintained in order to maintain GFR?
Net filtration pressure (NFP)
GFR is maintained by autoregulation if MAP is ______?
Between 80-180 mmHg
What GFR rate is used as an overall threshold for inadequate kidney function?
< 60 mL/min
MAP needed for autoregulation/maintenance of adequate GFR in a healthy individual?
“In theory” if MAP > or = 60 mmHg
**Higher MAP values are used for clinical thresholds
What occurs when MAP drops too low to maintain NFP and GFR?
Acute renal insufficiency
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
What is the universal recommendation to avoid/minimize progression of acute renal insufficiency?
Maintain MAP > or = 65 mmHg
Evidence suggests that maintaining a MAP within 72-82 mmHg or more could be necessary to avoid acute renal insufficiency in patients with which conditions?
Acute septic shock and initial renal function impairment
What is chronic kidney disease (CKD)?
Abnormal kidney structure and/or dysfunction for >3 months that impacts health
Diagnostic criteria for CKD?
At least one of the following for at least 3 months:
-GFR < 60 mL/min
-objective measure of kidney damage/dysfunction: proteinuria, hematuria, abnormal electrolyte balance d/t renal cause, renal abnormalities detected by histology/imaging, kidney transplant
Stage 1 CKD values?
GFR >/= 90 mL/min, objective markers present
Stage 2 CKD values?
GFR = 60-90 mL/min, objective markers present
Stage 3 CKD values?
GFR = 30-59 mL/min, objective markers present or absent
Stage 4 CKD values?
GFR = 15-29 mL/min, objective markers present or absent
Stage 5 CKD values?
GFR = < 15 mL/min, objective markers present or absent
Ongoing evidence based guidelines are being developed to create other staging models for GFR that predict what?
Outcome risks
Intrinsic signaling of the kidney?
Renal autoregulation by two mechanisms: myogenic feedback and tubuloglomerular feedback
*concerned with trying to maintain ideal GFR
Kidney is very effective at autoregulation if MAP remains between what values?
80-180 mmHg
Extrinsic signaling of the kidney?
SNS and RAAS signaling influence GFR
*concerned with trying to maintain BP (influences GFR to maintain BP)
Autoregulation principles of glomerular arterioles?
-Afferent arteriole/blood entering glomerular capillary
-Efferent arteriole/blood leaving glomerular capillary
*will contract or dilate to alter filtration
What happens to filtration if the afferent arteriole constricts and/or the efferent arteriole dilates?
Filtration decreases
What happens to filtration if the afferent arteriole dilates and/or the efferent arteriole constricts?
Filtration increases
What is the myogenic feedback mechanism of intrinsic signaling?
Mechanical increase/decrease in pressure on arteriole wall SM stimulates contraction or relaxation reflex
–> if systemic BP increases: myogenic feedback will relax or constrict afferent arteriole to adjust GFR and NFP
What happens during myogenic feedback if there is an increase in systemic BP?
Stimulates vasoconstriction of afferent arteriole (decreases excess GFR created by high systemic BP)
What happens during myogenic feedback if there is a decrease in systemic BP?
Stimulates vasodilation of afferent arteriole (increases low GFR created by low systemic BP)
What is the tubuloglomerular feedback mechanism of intrinsic signaling?
Macula dena monitors amount of NaCl flowing in the DCT
–> if too much/too little NaCl flow, signals JGA to adjust GFR/restore optimal NaCl flow in the DCT
What happens during tubuloglomerular feedback if GFR is elevated?
Elevated GFR –> increases NaCl flowing through DCT
Macula densa detects increased NaCl and signals juxtaglomerular (JG) cells to release ATP and adenosine
–> ATP and adenosine stimulate mesangial cells of afferent arteriole to constrict, decreasing GFR (restoring optimal NaCl flow through DCT)
What happens during tubuloglomerular feedback if GFR is low?
Decreased GFR –> decreases NaCl flowing through DCT
Macula densa detects decreased NaCl and signals juxtaglomerular (JG) cells to release nitric oxide and prostaglandins
–> NO and prostaglandins stimulate mesangial cells of afferent arteriole to relax, increasing GFR (restoring optimal NaCl flow through DCT)
What effect do NSAIDS have on GFR/tubuloglomerular feedback?
Excess NSAID use can inhibit prostaglandin synthesis and signaling & may gradually decrease GFR
**Chronic use can induce kidney injury
What is the role of SNS in extrinsic signaling of the kidneys?
Stimulates afferent arteriole vasoconstriction, decreasing GFR and NFP
During times of stress, exertion, or hypovolemic shock, the SNS will do what?
-Vasoconstrict most BV –> increases systemic BP
-Directly decreases GFR by constriction of the afferent arteriole/rediraction of blood flow to other regions with increased need and/or to keep the body alive
What is the role of the RAAS (renin angiotensin aldosterone system) in extrinsic signaling of the kidneys?
Low systemic BP and SNS signal JGA cells in kidney to release renin –> renin converts angiotensinogen to angiotensin I –> ACE1 found in BV of lungs/glomerulus/other organs converts angiotensin I to angiotensin II
*angiotensin II stimulates the adrenal gland to release aldosterone (stimulates nephron to retain sodium while ADH allows water to follow)
What is the effect of angiotensin II on GFR?
Vasoconstricts afferent and efferent glomerular arterioles
*acts primarily on the efferent arteriole, has very small vasoconstrictive effect on afferent arteriole
Net effect: vasoconstriction of efferent arteriole–> increases GFR
ACE-I/ARBs effect on RAAS/GFR?
Relax efferent arteriole –> decreases GFR
ACE-I: block conversion of angio I –> agio II (less angio II)
ARBs: block antio II R’s (angio II can’t constrict BV)
What structures make up the renal corpuscle?
Glomerulus, Bowman’s capsule
Why are ACE-I and ARB effects a non-issue in kidneys with normal renal bloodflow?
ACE-I/ARBs may decrease GFR, but kidney is able to autoregulate/maintain GFR
Why are ACE-I and ARB effects a potential issue in kidneys with poor renal bloodflow (renal artery stenosis, etc.)?
ACE-I/ARBs may decrease GFR, and kidney may not be able to autoregulate/maintain GFR d/t poor renal bloodflow
Effect of natriuretic peptides (extrinsic signaling) on RAAS and GFR?
Counteracts RAAS, influence GFR
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are produced and secreted from what?
The heart and brain
How to ANP and BNP increase GFR?
Vasodilate glomerular afferent arteriole, stimulates diuresis and natriuresis
Inhibit aldosterone, renin (RAAS) and sympathetic influence on kidney
What is renal natriuretic peptide secreted by and what is its role on the kidneys?
Urodilation- stimulates natriuresis and diuresis
Secreted by: DCT/collecting ducts
What is C-type natriuretic peptide (CNP) produced/secreted by and what is its role on the kidneys?
Decreases systemic BP (vasodilates), may increase GFR
Produced/secreted by: vascular endothelium
Renal artery stenosis (RAS) can cause what form of HTN?
Renovascular HTN
Renal artery stenosis (RAS) decreases bloodflow to the kidneys and causes what?
Decreased GFR, Decreased NaCl flow through DCT
Dec. NaCl flow stimulates renin release–>stimulates RAS causing HTN
Why is renal artery stenosis (RAS) considered the silent killer?
Often does not cause signs/sx until RAS becomes severe
When should you suspect renal artery stenosis (RAS)?
Abnormal onset of HTN: HTN onset at young age, HTN worsens abruptly, kidney signs/sx, atherosclerosis in other arteries
