Renal Flashcards
What is the main physiological function of the kidneys?
Maintenance of the composition and volume of extracellular fluid
What is extracellular fluid?
Fluid outside cells, but on the serosal side of epithelial tissues
So, bladder urine, GI tract fluid, and lung fluid are not ECF
How much extracelular fluid do we have? What are the 2 main compartments?
15 L
12L interstitial fluid
3 L Plasma
How do we maintain homeostasis of stuff in the extracellular fluid?
Through urine production
What are the 2 capillary beds of the kidneys?
Glomerular
Peritubular
What is glomerular filtration?
Filtration of plasma into the tubule.
Allows water and solutes in, but retains larger colloids
What is the filtration fraction? What is its normal value?
Amount of renal plasma flow filtered at the glomerulus.
20% of renal blood flow
What induces the kidneys to secrete renin? (3)
Activation of renal beta-sympathetic nerves
Stimulation of renal baroreceptors by decreased arteriolar pressure
Activation of macula densa chemoreceptor by reduced delivery of NaCl to the distal rubule
Which cells in the kidney secrete renin? Where are they? What structure are they part of?
Granular cells, in the afferent arteriole going to the glomerulus
Juxtaglomerular apparatus
The molecular sieving process of the glomerulus is also called _______________
Ultrafiltration
What is filterability a function of?
Molecular size
What are the 3 filters of the glomerulus?
Fenestrated epithelium
Basal lamina
Podocytes
What is the charge of the basal lamina?
Negative, so negatively charged things don’t get through
Mathematical description for GFR
GFR = dP/R = KdP = K(Pgc-Pt-Pigc)
Pressures of glomerular capillary, tubule, colloid osmotic pressure)
What are 2 forces that oppose glomerular filtration?
Tubule diameter -> backpressure = Pt
Colloid osmotic force
What is the net filtration pressure?
Sum of glomerular capillary, tubule, colloid osmotic pressures
What do mesangial cells do? (3)
Secrete matrix continuous with basal lamina
Do some macrophage-like things (make cytokines, etc)
Unclear role in contraction of glomerular capillary loops
Is glomerular capillary pressure dependent on mean arterial pressure?
No. It is very tightly autoregulated
What is the glomerular response to chronic hypotension?
Both the afferent and efferent arterioles constrict
This decreases flow through the glomerulus (so it can go to other organs) but sort of maintains Pgc (glomerular capillary pressure)
3 baroreceptors that affect glomerular arterioles
Baroreceptors in main arteries -> sympathetic response
External baroreceptors -> antiogensin II constricts
Intrarenal baroreceptors -> RAAS
Where are renal interstitial cells located? What do they do?
Located in kidney medulla between renal pyramids
Make renal prostaglandins
When are renal prostaglandins produced? What do they do?
Secreted in response to angiotensin II
Dilate renal arterioles -> maintain adequate renal blood flow, maintain GFR. This blunts effects of hypovolemic mechanisms so the kidney doesn’t get ischemic
Compare autoregulation and hypovolemic response:
Responds to Purpose Arterioles involved Mechanism of arteriolar changes Location of mechanism
mrr
What do the minor calyxes do? Major calyx?
Drain renal pyramids
Drain minor calyxes
What do the medullary pyramids contain?
Nephrons and collecting ducts
What is the path of the renal arteries to veins?
Renal artery -> anterior and posterior segments -> interlobar (between medullary pyramids) -> arcuate arteries (parallel to outer capsule) -> interlobular -> afferent arterioles -> glomerular capillary -> efferent arterioles -> vasa recta ? -> peritubular capillary -> interlobular veins -> arcuate veins -> interlobar veins -> renal vein
What part of the kidney are renal corpuscles located in?
Cortex
What part of the kidney are renal tubules in?
Medulla
What kind of epithelium is in the proximal tubule?
Cuboidal with brush border
What does the proximal tubule transport?
Na/K ATPase for pumping sodium out of the basolateral side
What is the epithelium like in the thin loop of Henle?
Simple squamous
What is the epithelium like in the thick loop of Henle?
Cuboidal
What is the epithelium like in the distal tubule?
Cuboidal
Where do aldosterone and antidiuretic hormone act in the kidney?
Distal tubule
What two hormones act on the distal tubule?
Aldosterone
Antidiuretic hormone
The distal convoluted tubule is physically connected to the region near the vascular pole through the _______
Macula densa
Where are the Lacis cells located?
Between macula densa and mesangial cells
What is another name for antidiuretic hormone?
Vasopressin
What is the major osmotic substance in the ECF?
Sodium
Where are the osmoreceptors?
Supraoptic nucleus of the hypothalamus
What makes antidiuretic hormone?
Hypothalamus (specifically, the supraoptic nucleus)
OR maybe the pituitary
Mental states with increased risk of suicide
Hopelessness
Helplessness
Impulsivity
Are all patients who kill themselves depressed?
No
How do you protect against suicide in schizophrenia?
Clozapine
What CSF substance is associated with an increased risk of violence and suicide?
5-HIAA (hydroxyindoleacetic acid)
What are 2 groups of people who are at high risk of completing suicide?
Single male who lives alone
Chronic physical illness
7 psychiatric illnesses that predispose to suicide
Depression Schizophrenia Bipolar mood disorder Drug or alcohol problems Cognitive disorder Anorexia nervosa Personality disorder with axis I co-morbidity
When is risk of suicide highest in renal disease? What does this mean?
First 3 months of dialysis
Suicide is prompted by failure to cope with stress rather than declining health status
5 errors made in the evalulation of psychiatric patients
Not corroborating story with family/friends
Not reviewing old records
Not seeking consultation
Avoiding specific questions about guns, plans, fantasies, etc
Ignoring risk enhancing factors
How much fluid is in the intracellular compartment? What are the 2 parts?
27L
Noncirciulating cell volume = 24L
Blood cells = 3L
What are the insensible water losses?
Respiration, skin
The ones you can’t sense I guess
How much of the cardiac output do kidneys recieve?
25%
Why do filtration and reabsorption rates»_space; excetion rates?
Rapid removal of waste products
Precise and rapid volume/composition control of ECF
What important calcium-related substance does the renal system make?
Calcitriol
What is the rate-limiting step of the RAAS?
Renin
What happens to net filtration pressure as we move along the tubule?
It decreases and eventually reaches equilibrium
This is because Pi gc increases and Pgc-Pt decreases
What 2 things make up K, the resistance term in GFR = dP*K?
Hydraulic conductivity
Surface area
K = pA
What 2 things determine filtration fraction?
FF = GFR/RPF
RPF = renal plasma fraction
Which arteriole does angiotensin II act on?
Both, but mostly the efferent (away) one
How do NSAIDS affect the kidneys?
They block prostaglandins, vasoconstricting the afferent arteriole
How do ACEIs and ARBs affect the kidneys?
They block angiotensin II, increasing renal blood flow but decreasing GFR
What is the pH of the urine of carnivores and herbivoes?
Carnivores - acidic
Herbivore - alkaline
What are the 2 sides of the epithelial cells in the renal tubules?
Apical - faces lumen
Basolateral - faces serosa (interstitium and capillaries)
What side are microvilli on?
Apical
How many ions/molecules does a facilitated diffusion carrier take?
At least 2 (why not 1?)
What side is the Na/K ATPase on? Which directions does it transport?
Basolateral
3 Na out, 2K in
What are the jobs of the nephron segments?
Proximal convoluted tubule - bulk reabsorption
Loop of Henle - urine dilution
Distal convoluted tubule - tine-tuning Na balance
Collecting duct - fine-tuning K, acid, water ballance
10 things the proximal tubule cell does
Bulk reabsorption of: Na, water, glucose, amino acids, calcium, phosphate, citrate
H+ secretion/HCO3 absorption
Organic anions secretion
Macromolecule absorption
Is the thick ascending limb permeable to water?
No
What 3 things are reabsorbed in the thick ascending limb?
Na (trans-Na/K/2Cl cotransporter and paracellular)
Ca (paracellular)
Mg (paracellular)
What 3 things are reabsorbed in the distal convoluted tubule?
Na (Na/Cl cotransporter)
Ca
Mg
Where do thiazide diuretics act?
Distal convoluted tubule NaCl cotransporter
2 types of cells in the collecting duct
Principal cells Intercalated cells (alpha, beta)
What do principal cells do (3)?
Fine tune Na (ENaC), K (ROMK/Maxi), water (aquaporin) reabsorption in the collecting duct
What do alpha intercalated cells do?
H+ secretion
HCO3- synthesis
K+ absorption
What do beta intercalated cells do?
HCO3- secretion
CL- absorption
What does aldosterone do to the principal cells in the collecting duct?
Increases Na+ transporters so Na+ goes into the blood
What does vasopressin do the collecting duct?
Allows it to be permeable to water via aquaporins
How does tubular function depend on flow?
Higher velocity - less time for interaction with transporters -> less absorption
Reduced flow rate increases absorption
How do receptors for ECF volume work?
Stretch
4 effects ofsympathetic activity on the kidney
Vasoconstriction
Renin release
Decreased RBF/GFR
Increased renal reabsorption of NaCl
Where is aldosterone made?
Adrenal gland
What does vasopressin do?
Induces expression of aquaporins on collecting duct cells so water can escape out of the urine
8 non-osmotic stimuli for vasopressin
Low effective arterial blood volume Endocrine disorder Pain Nausea CNS disorders Pulmonary disorders Drugs Meds
What are the normal values for PO2
PCO2
and HCO3
94 +-8
38 +-2
24 +-2
What defines acute kidney injury?
Rapid reduction in glomerular filtration rate manifested by a rise in plasma creatinine and urea concentration
What state does acute kidney injury result in?
Reduced clearance of nitrogenous waste products
-> azotemia
What are 3 problems that can cause acute kidney injury?
Pre-renal azotemia - decreased GFR from decreased renal plasma flow or renal perfusion pressure
Post-renal azotemia or obstructive nephropathy - decreased GFR due to obstruction of urine flow
Intrinsic renal disease - decreased GFR from direct injury to the kidneys
What is oliguria?
What is anuria?
Decreased urine (
What is the most common cause of an abrupt decrease in GFR in a hospitalized patient?
Prerenal azotemia
What are 2 hypervolemic states that can cause pre-renal azotemia?
Congestive heart failure
Cirrhosis
These diseases are characterzed by low effective arterial blood volume and reduced renal perfusion
4 types of kidney diseases that cause acute kidney injury
Vascular (cholesterol emboli, renal vein thrombosis)
Glomerular (acute glomerulonephritis, hemolytic uremic syndrome)
Interstitial (acute interstitial nephritis, infection, myeloma kidney)
Tubular (ischemic or nephrotoxic acute tubular necrosis)
Where in the nephron do urinary casts usually form
Distal convoluted tubule
2 common causes of death in patients with acute tubular necrosis
Infections
GI bleed
What is the primary protein in the slit diaphragm of pedicels?
Nephrin
Why should we care about microalbuminuria?
Suggestive of early glomerular damage
We look for it in diabetics to predict diabetic nephropathy
What is nephrotic syndrome?
What is nephritic symdrome?
Nephrotic - protein leak through glomerular capillary wall
Nephritic - glomerular injury
5 things altered in nephrotic syndrome
Protineuria Hypoalbuminemia Edema Hyperlipidemia Lipiduria
What are the 2 mechanisms by which edema occurs in nephrotic syndrome?
Decreased serum albumin
Defect in sodium excretion -> volume expansion
Why is there hyperlipidemia and increased risk for thrombosis in nephrotic syndrome?
The liver tries to make more albumen and it also makes more of all proteins, including lipoproteins and clotting factors
6 things altered in nephritic syndrome
Microhematuria (sometimes casts) Leukocyturia Proteinuria Decreased GFR Hypertension Edema
3 genes most commonly mutated in hereditary glomerular disease
Nephrin
Podocin
WT-1
How do you treat hereditary glomerular disease?
ACEI
Renal transplantation eventually
Steroids don’t work
What is the mechanism of minimal change disease?
A circulating permeability factor acts directly on the podocyte, disrupting the permeability barier so proteinuria occurs
What molecule is expressed with minimal change disease?
CD80
What is the treatment for minimal change disease?
Steroids
What genetic polymorphism is more common in focal segmental glomerulosclerosis?
APOL1
What is membranous nephropathy?
Deposition of immune complexes in subepithelial space - glomerular basement membrane looks thickened
What is the antigen n membranous nephropathy?
Something on the podocyte, usually PLA2
What is the histologic pattern in membranoproliferative glomerulonephritis?
Mesangial proliferation
Thickening of glomerular basement membrane
C3 and IgG deposits
Membranoproliferative flomerulonephritis type 1 is associated with what infection?
Hepatitis C
What 2 diseases exhibit pulmonary-renal syndrome?
Goodpasture’s
ANCA-associated vasculitis
Crescents are ssociated with what disease process?
Rapidly progressing glomerulonephritis
Where are crescents? What 2 cells types are they made of?
Bowman’s capsule
Macrophages and parietal epithelial cells
Which infection is most common before post-infectious glomerulonephritis?
Group A strep (GAS)
In IgA nephropathy, wheredoes IgA usually deposit?
Mesangium
What is the mechanism of IgA nephropathy?
IgAs have abnormal sugars and are not cleared as easily, resulting in circulating complexes
What is the systemic disease that results in IgA nephropathy?
Henoch-Schonlein purpura
What is a pauci-immune renal vasculitis
Small vessel vasculities of the kidneys without evidence of immune complex deposition
What autoantibody is often present in pauci-immune renal vasculitis?
ANCA
What are the 2 most common antigens for ANCA?
Myeloperoxidase
PR-3
Cryoglobulins are most frequently associated with ________ infection
Hepatitis C
What do maltese crosses and oval fat bodies refer to?
The refractile pattern of lipiduria
3 complications of nephrotic syndrome
Hypercoagulability
Increased infections
Less vitamin D
3 things in general management of nephrotic syndrome
Low-salt diet
Diuretics
Blood pressure control
What is the main pathologic change in minimal change disease? What imaging modality is used to see it?
Elecron microscopy shows foot process fusion (but really foot processes are disrupted and proteinuria occurs)
What are 3 diseases associated with focal segmental glomerulosclerosis?
HIV associated nephropathy
Sickle cell
Obesity
What toxin can lead to membranous nephropathy?
Mercury
What is abnormal in membranoproliferative glomerulonephritis type II?
Low C3 and C4 via the alternative complement pathway
Are adjacent podocyte feet from the same cell or different cells?
Different! They alternate
5 clinical syndromes of glomerular disease
Asymptomatic hematuria/proteinuria
Acute nephritic syndrome (hematuria/protinuria + ARF)
Rapidly progressive nephritic syndrome
Nephrotic syndrome (massive proteinuria, hypoalbuminemia, edema)
Chronic renal failure
What are the 6 ‘nephritic’ diseases?
Benign familial hematuria (thin basement membrane disease)
Alport’s disease
IgA nephropathy
Postinfectious glomerulonephritis
Focal necrotizing/crescentif glomerulonephritis
Lupus glomerulonephritis
What is mutated in both thin basement membrane disease and Alport’s disease?
Collagen IV
What is the triad of Alport’s disease?
Nephritis
Deafness
Ocular lesions
What is the inheritance pattern of Alport’s disease
X-linked
I presume recessive
What population does Henoch-Schonlein Purpura most commonly occur in?
A starry sky immunoflourescence pattern occurs in which disease?
Postinfecious glomerulonephritis
What is the difference between membranous disease and membranoproliferative disease (both 1 and II)
Immune aggregates between the basement membrane and the podocyte
Immune aggregates in the basement membrane
I - antibodies
II - complement
3 types of IF staining in focal segmental necrotizing and crescentic glomerulonephritis
Linear - basement membrane itself is the antigen (Goodpasture’s, anti-GBM)
Granular - immune complex-mediated (IgA, SLE, endocarditis, etc)
No staining - pauci-immune (vasculites)
What is the difference between Goodpasture’s and anti-glomerulobasement membrane disease?
Renal limited: AGBM
Renal + lung: Goodpasture’s
What Ig is anti-GBM and Goodpasture’s?
IgG
What are the 6 renal lupus classifications?
I: No or minimal changes II: Mesangial glomerulitis III: Focal, segmental glomerulonephritis IV: Diffuse glomerulonephritis V: membranous nephropathy VI: Renal failure
2 mechanisms of hyperfiltration injury
Circulating factors
Mechanical stress
What 4 things are associated with membranous glomerulopathy 15% of the time?
Bugs - infections
Drugs - rheumatoid meds
Tumors
Rheum - SLE
What is the mechanism for membranoproliferative glomerulonephritis?
Subendothelial deposits cause injury to the endothelial cell
It retracts and puts a new layer of basement membrane between the deposit and itself
Is renal amyloidosis hypo or hypercellular?
Hypocellular - amyloid deposits wipe out the glomerulus and deposit in vessels
What does amyloidosis look like on EM?
Spilled spaghetti
What 2 kidney lesions does diabetes cause?
Hyaline arteriolar disease
Diabetic glomerulosclerosis
What happens in diabetic glomerulosclerosis?
Expansion of the mesangium
Basement membrane thickening
Mesangial lysis (they make so much basement membrane they kill themselves)
Wat is the gross appearance of the kidney in hypertensive renal disease?
Finely granular surface fromscarred glomeruli
What happens to the kidney in hypertensive renal disease (2)?
Medial and intimal thickening
yaline deposition
What happens in malignant/accelerated hypertensive renal disease?
Renal vasculature injury
- > fibrinoid necrosis, hyperplastic arteriolitis (ok inflammation)
- > increased renin
- > viscious cycle
What is uremia?
Dysregulation of stuff when there is severe loss of all renal functions
3 other things that get fucked up when your kidney is really fucked
Erythropoietin -> anemia
Renin -> hypertension
Vitamin D -> osteomalacia
Within what time frame must urinalysis be done in?
2 hours of collection
Or refrigerated if longer (but less than 24 hours)
What can cause a false positive on a urinalysis glucose screen? A false negative?
Jar is left open
Vitamin C
What does nitrite in the urine mean?
Gram negative bacteria
What do hyaline casts indicate?
They are normal
Hypo and hypernatremia refer to the concentration of sodium where?
In the serum
NOT total body
Urine can be _____ times more concentrated than plasma
4
What 2 things does ADH/vasopressin do?
Increase renal water reabsorption
Vasoconstriction
What is hte most common electrolyte disturbance in hospitalized patients?
Hyponatremia
What is a common mechanism of hyponatremia? What are 2 ways this can occur?
Elevated serum osmolality from a solute other than sodium
Hyperglycemia
Mannitol/glycerol administration
2 conditions that cause isotonic hyponatremia
Lab artifact:
Hyperlipidemia
Hyperproteinemia (like multiple myeloma)
Explain lab artifact isotonic hyponatremia
Plasma osmolality is normal but there is less water content *because of hyperlipiedmia or hyperproteinemia)
It is a laboratory artifact of flame photometry and a sodium-sensitive electrode will yield a normal value
Deficiency in what hormone causes hypovolemic hyponatremia?
What about euvolemic hyponatremia?
Mineralocorticoid
Glucocorticoid
4 causes of hypervolemic hyponatremia
Congestive heart filaure
Hepatic cirrhosis
Nephrotic syndrome
Advanced chronic or acute renal failure
What is serum osmolality like in hypernatremia?
It is always increased
What is diabetes insipidus?
Excessive thurst and excretion of lots of dilute urine. Reuction of fluid intake does not concentrate urine
What are the 2 kinds of diabetes insipidus?
Central - ADH/vasopressin is not made
Nephrogenic - insensitiity to ADH/vasopressin
Equation for amount of water needed to treat someone with hypernatremia
0.6*body weight in kg * [actualNa/desiredNa-1]
What is effective arterial blood volume?
Volume of blood detected by volume sensors in the arteries
What are the 4 categories of volume sensors?
Low-pressure baroreceptors - veins
High-pressure baroreceptors - carotid and aortic body
Intrarenal sensors
Hepatic and CNS sensors
What is the end product of the RAAAS?
Aldosterone
4 substances that decrease sodium reabsorption
Natriuretic peptides
Prostaglandins
Bradykinin
Dopamine
4 substances that increase sodium reabsorption
Angiotensin II
Aldosterone
Catecholamines
Vasopressin/ADH
What does sympathetic stimulation do to natriuresis?
Increases sodium reabsorption
What are 3 ways Na gets reabsorbed in the distal colvoluted tubule?
- Na channels
- NaCal cotransporter
- Na/H antiporter
These are all on the luminal side
How does sodium get into the principal cells of the cortical collecting duct?
Na enters and is exchanged for K
What is Bartter’s syndrome? Where in the kidney is the defect?
A mutation in the Na/K/2Cl cotransporter in the thick ascending loop of Henle?
Hypokalemia Hypomagnesemia Metabolic alkalosis High renin High aldosterone Increased calcium excretion Normal blood pressure
What is Gitelman’s syndrome? Where in the kidney is the defect?
A mutation in the Na/Cl cotransporter in the distal tubule
Hypokalemia
Hypomagnesemia
Metabolic alkalosis
Reduced excretion of calcium