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Renal > Lecture 1: Renal Tissue and Cellular Structure > Flashcards

Lecture 1: Renal Tissue and Cellular Structure Flashcards

1
Q

What are the functions of the kidney?

A

maintain salt and water balance
excretion (filtration, reabsorption, secretion)
endocrine
metabolic

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2
Q

What are some substances that are filtered by the kidney? Where does filtration occur?

A

products of protein metabolism

at glomeruli

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3
Q

what are some substances that are reabsorbed by the kidney?

A

water, glucose, amino acids, sodium, bicarbonate reabsorbed in the tubules

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4
Q

what are some substances that are secreted by the kidney?

A

drugs (penicillin, contrast dyes) by the ABC (ATP binding cassette) transporters shuttle lipophillic substances across the tubular membranes

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5
Q

What are some of the endocrine effects of the kidney?

A

renin –> retention of Na+ and H2O
erythropoietin –> stimulates maturation of RBCs
local effects: prostaglandins and kinins - effect local blood flow through the kidney

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6
Q

What are some of the metabolic effects of the kidney?

A

peptide hormones like PTH and insulin are degraded in the kidney
Vitamin D is converted to active form: 1,25 dihydroxyvitamin D3.
gluconeogenesis occurs during hypoglycemia
citrulline converted into arginine as part of the urea cycle’s process of NH4

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7
Q

What are some of the microscopy techniques?

A

light microscopy, electron microscopy, immunofluorescnece microscopy

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8
Q

Describe light microscopy.

A

H&E –> examine overall kidney morphology
Periodic Acid Schiff’s stains proteoglycans and appreciate thickness of basement membrane and ECM
Mallory trichome stain –> assess degree of collagen deposits in the interstitial matrix
silver stain visualizes fine collagen III in matrix

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9
Q

Describe the use of electron microscopy

A

ultrastructural examination is essential for diagnosis of glomerular disorders

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10
Q

Describe the use of immunofluorescence microscopy

A

antibodies labeled with fluorescein bind to immunoglobins, C3 or C4, which may accumulat in renal pathologies

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11
Q

What are the physical elements that are examined in a renal biopsy?

A

glomeruli
tubules
interstitum
blood vessels

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12
Q

what are the 6 main sections of the nephron?

A

bowman’s capsule
proximal tubules
thin limbs of the loop of Henle (descending and ascending)
thick ascending limb of the loop of Henle
distal convoluted tubule
collecting duct

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13
Q

what blood vessels are bowman’s capsule related to?

A

the glomerulus for function of the tubular segment

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14
Q

what blood vessels are the proximal and distal tubules related to?

A

peritubular capillaries for reabsorption and secretion

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15
Q

what blood vessels are the loops of Henle related to?

A

vasa recta which produces a hypertonic interstitium to alter tonicity of excreted urine

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16
Q

what are the descriptive terms used to describe locations of a nephron?

A

superficial, midcortical, juxtamedullary

based on the locations of the glomerulus

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17
Q

what is the glomerulus?

A

the filtration unit of the kidney
it is formed by blood vessels, epithelium of the nephron tube (bowman’s capsule), intervening basement membrane and stalk of support cells (mesangial cells)
the entering afferent arteriole and exiting efferent arteriole cluster at the vascular pole of the glomerulus
at the opposite end the nephron tubule exits glomerulus at the urinary pole

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18
Q

how much blood is filtered through the kidney?

A

20% of the blood volume leaving the heart
1L/min of the 5L/min total CO
produce 180 L of filtrate every 24 hours, but excrete 1-2 L:

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19
Q

Describe the blood vessel.

A

afferent arterioles form glomerular capillaries where filtration occurs
capillary endothelium is fenestrated with no diaphragms spanning the pores
patent capillary loops are a histological landmark in light and EM
capillaries merge to form the efferent arteriole
arterioles are surrounded by smooth muscle that affect filtration pressure in the glomerular capillaries

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20
Q

what is the bowman’s capsule ade of?

A

parietal epithelium - simple squamous forming the outer wall of the urinary space
at vascular pole it is continuous with visceral epithelium of Bowman’s capsule which reflects over glomerular tuft of capillaries
at the urinary pole, the pariental epithelium is continuous with the proximal tubule

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21
Q

what is the visceral epithelium of Bowman’s capsule made of?

A

podocyes which have processes or trabeculae that interdigitate with neighboring podocytes forming a series of foot processes (pedicels)
the spaces between foot processes are spanned by a filtration slit diaphragm, which are a specialized junctional complex

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22
Q

What is nephrin?

A

transmembrane proteins of the immunoglobulin superfamily which form homodimers to link neighboring foot processes

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23
Q

what are the intracellular linkage molecules that interface between nephrin and actin cytoskeleton?

A

ZO-1, alpha-acctinin4, pododcin

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24
Q

What are the pedicels coated with?

A

podocalyxin, which is a glycoprotein rich in negatively charge sialic acid

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25
Q

what are pedicels important for?

A

glomerular filtration

fusion of the pedicels occur pathologically

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26
Q

where is the glomerular basement membrane?

A

between the glomerular capillary endothelium and the podocyte foot processes

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27
Q

what are the three layers of the glomerular basement membrane?

A

lamina rara externa: in contact with glomerular podocytes
lamina densa: central dense layer
lamina rara interna: contacts the capillary endothelium

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28
Q

describe the central lamina densa

A

enriched with collagen type IV limiting porosity to less than 40,000 daltons

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29
Q

describe the laminae rar interna and externa

A

contain anchoring proteins laminin and fibronectin as well as heparan sulfate-rich anionic proteoglycans repelling negatively charge plasma proteins

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30
Q

what disease occurs as a result of a decrease in basement membrane heparan sulfate?

A

proteinuria, seen in diabetes

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31
Q

what are the three histological layers comprising the glomerular filtration barrier?

A

fenestrated endothelium
glomerular basement membrane
foot processes with filtration-slit diaphragm

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32
Q

what determine glomerular filtration rate?

A

hydrostatic pressure (BP) within the glomerular capillaries and oncotic pressure from the plasma proteins

33
Q

what fine tunes the GFR?

A

smooth muscle in the media of both the afferent and efferent arterioles and contractile intraglomerular mesangial cells

34
Q

what are intraglomerular mesangial cells?

A

connective tissue cells that are either smooth-muscle like mesangial cells or bone marrow-derived macrophages

35
Q

what are smooth muscle like mesanial cells?

A

contractile (express alpha-actin) and may decrease surgace area available for filtration
sensative to angiotensin II
they synthesize the ECM components: collagen (IV and V, more I and III, when activated by cytokines), fibroonectin, thrombospondin, laminin, vitronectin and proteoglycans, enzymes involted in turnover of ECM (metalloproteinases and serine-proteases)
secrete PGs - vasodilation of glomerular arterioles
secrete hormones, cytokine,s GFs and paracrine agents

36
Q

What do bone-marrow derived macrophages do?

A

phagocytose apoptotic cells and material lodged in the basement membrane
utilize C3b or Fc receptors to bind opsonized particles
they express MHC class II antigens on surgace and act as APC

37
Q

What is reabsorbed in proximal tubule?

A 
65-70% water, Na, K
all glucose, amino acids, citrate, small peptides
80% bicarbonate
40-50% Ca2+
80 - 95% of PO4-
38
Q

what are segments of the proximal tubule?

A

physiogically (different transporters): S1, S2, S3

anatomically: proximal convoluted tubule and proximal straight tubule

39
Q

describe the convoluted portion of the proximal tubule.

A

coil and occupy much of the cortex around the glomeruli

proximal straight tubules are part of the medullary ray (cluster of straight tubules in the cortex) en route to medulla

40
Q

describe the proximal straight tubule

A

part of medullary ray; cluster of straight tubules en route to medulla

41
Q

what some of the features of the proximal tubule epithelium?

A

simple cuboidal with large prominent nucleus and

surface specializations

42
Q

what are some features of the apical plasma membrane

A

it folds as tall, regular microvilli = brush border
carriers inserted iinto this increased surface area for secondary active transport of reabsorbed amino acids, glucose, citrate and bicarbonate ions
the ions are couples with Na+ ions in positively charged carrier complexes
apical tight junctions are less frequent than other tissues, desmosomes are infrequent

43
Q

what are claudins?

A

they are in the tight junctions of proximal tubule epithelium that create a leaky epithelium that permits paracellular movemet of water and Ca2+ from lumen to interstitial space below epithelium

44
Q

what is the endocytic apparatus?

A

it is in the apical cytoplasm and consists of vesicular invaginations between bases of microvilli, clathrin coated vescles, large vacuoles lysossomes and condensin vacuoles
peptides from filtrate are endocytosed here and degraded before release outside the basolateral side

45
Q

what is megalin

A

a specific endocytosis receptor for albumin and small proteins recovered in the proximal tubule
it is downregulated by TGF0beta during inflammatory conditions which contribute to proteinuria

46
Q

What drugs inhibit endocytosis contributing to proteinuria?

A

HMG-Coa inhibitors, like statins

47
Q

Describe the basolateral plasma membrane

A

extensive folding
Na+K+ATPase transporters pump Na+ out of cell into basolateral extracellular space
cytoplasmic mitochondria occupy foldes between basolateral invaginations providing ATP for active transport

48
Q

what are the portions of the loop of Henle?

A

thin descending limb
thin ascending limb
medullary thick ascending limb (mTAL)
cortical thick ascending limb (cTAL)

49
Q

Describe the variation in the lengths of the loops of Henle.

A

superficial glomeruli have very short loops of Henle

juxtamedullary glomeruli have very long loops that extend to tips of the medullary papillae

50
Q

what are some features of the loop of henle?

A

establish hypertonic interstitium in the medulla, which is essential to production of concentrated or hypertonic urine
there is a countercurrent exchange between the tubules and the vasa recta which maintains the hypertonic interstitum

51
Q

What are some physiological features of the thin portions of the loop of Henle?

A

Simple squamous epithelium
Thin descending limb is permeable to water and urea but impermeable to Na+ and Cl-
Water and urea passively move frome the tubular fluid into interstitium as thin limb descends into hypertonic interstitium of medulla
Water moves paracellularly through shallow tight junctions and intracellularly through aquaporin channels
Into the ascending thin limb, the permeability characteristics reverse: impermeable to water and highly permeable to Na+ and Cl-. Salt exists the tubule as flow ascends into relatively less hypertonic regions of the medulla
Movement of water prevented by extensive tight junctions with claudins that seal and lack aquaporins
No active transport of Na+ or Cl- in the thin limb

52
Q

What is the main function of the thin limbs?

A

Along with the accompanying vasa recta, it maintains and stabilizes the hypertonic gradient of the medullary interstitium

53
Q

Where does the transition to the thick ascending limb of the loop of Henle take place?

A

Near the hairpin turn in short looped nephrons and at the transition from the outer to inner medullary zones in long looped nephrons

54
Q

Describe the thick ascending limb.

A

The luminal contents are hypotonic when they exit. Interstitum becomes hypertonic.
Simple cuboidal epithelial with numerous invaginations of the basolateral plasma membrane which is the site of Na+K+ATPase active transport pumps
The cytoplasm between the folds contains mitochondria (more round than ones in proximal tubule)
Electrical gradient powers ion movement
Apical plasma membrane: slightly irregular: contains Na+K+2Cl sympotrter: net movement of Ca+ and Cl- from lumen into interstium

55
Q

What inhibits the Na+K+2Cl- symporter?

A

Loop diuretics like furosemide

56
Q

How is the apical membrane distinguished?

A

Extensive tight junctions, which block paracellular movement of water since there are no aquaporins
Thick ascending limb is impermeable to water, claudins of the tight junction permit passage of Mg 2+, Ca2+ and Na+

57
Q

What is the macula densa?

A

Last segment of the cortical thick ascending limb
It returns to the glomerulus
Component of the juxtaglomerular apparatus – responsible for the secretion of rennin

58
Q

What is the distal convoluted tubule?

A

They are in the cortex intermingled with proximal convoluted tubules
Shorter length and a lower cuboidal epithelium
Apical surface is devoid of microvilli, resulting in a smooth lumen
Toght junctions are broader than proximal tubule with sealing claudins – precluding paracellular water movement
Impearmeable to water
Basolateral surface is highly folded with Na+K+ pumps and accompanying mitochondria
The basolateral active transport pumps are the driving force for the reabsorption of Na+ and Cl-
Responds to aldosterone to reabsorb Na+ and PTH to reabsorb Ca2+

59
Q

What are the parts of the collecting duct?

A

Connecting segment
Cortical collecting duct
Medullary collecting duct
Responsible for final adjustments to the colume and tonicity of the excreted urine
Controlled by vasopressin and aldosterone
Initially lined by simple cuboidal epithelium, as one progresses to the medullary papilla the epithelium becomes tall columnar and then pseudostratified at the exiting papillary ducts

60
Q

What does EM show of the collecting duct?

A

Principle (light) cells and intercalated (dark) cells

61
Q

What are principal cells?

A

Principal cells have a pale cytoplasm, small random mitochondria, few basal infoldings, very few microvilli and single cilium, which is a flow sensor mechanically linked to a Ca2+ channel
Respond to aldosterone by reabsorbing Na+ and secreting K+
Respond to ADH by increasing luminal permeability to water

62
Q

What are intercalated cells?

A

More electron dense cells (dark in EM), secrete H+ and play a large role in acidification of urine

63
Q

What is the goal of the structures of the juxtaglomerular apparatus?

A

Control GFR to not flood out the capacity of the distal nepron preventing excessive salt and water losses
The apparatus adjusts renal hemodynamics, during periods of increased or decreased perfusion and activates the RAAS cascade.

64
Q

What are the sensors in the juxtaglomerular apparatus?

A

Afferent arteriole stretch recptors and macula densa Cl-/osmolality receptors

65
Q

What are the components of the juxtaglomerular apparatus?

A

Afferent arteriole
Macula densa
Extraglomerular mesangial cells
Efferent arteriole

66
Q

Describe the afferent arteriole

A

Smooth muscle in the media are composed of juxtaglomerular cells which contain intracellular actin, myosin, and dense bodies like all smooth muscle cells, contain more RER, Golgi and a store of secretory vesicles (containing renin). The JG cells respond to a decrease in arteriolar stretch due to decreased BP by secreting renin granules. With elevated BP, the JG cells produce a myogenic response to vasoconstrict the afferent arteriole

67
Q

Describe the macula densa

A

The base of macula densa cells interdigitate with underlying extraglomerular mesangial cells and with JG cells. Nuclei are forced apically, toward the lumen, making this tubular section easy to identify. Respond to flow related alterations in level of Cl- (osmolality) in the fluid being delivered from the thick ascending limb. When Cl flow rates are high, the macula densa blocks release of renin by the JG cells. The macula densa acts on the JG cells of the afferent arteriole directly through the release of adenosine and NO, and indirectly via Angiotensin II and thromboxane

68
Q

Describe extraglomerular mesangial cells

A

Lie between the afferent arteriole, efferent arteriole, the macula densa and the glomerulus. Interact with the acula densa and JG cells assisting in regulation of renin secretion and vasoconstriction

69
Q

Describe the efferent arteriole

A

Smooth muscle contraction of the efferent artiole increases hydrostatic pressure within the glomerulus
In low pressure/flow – ang II causes constriction preserving GFR (vasoconstriction modulated by PGs which vasodilate the efferent arteriole to preserve blood flow to medulla)

70
Q

What is the renal interstitium

A

Connective tissue cells that are found between all of the tubular and vascular elements of the kidney

71
Q

Describe the renal interstitium in the cortex.

A

It has fibroblast like cells that make ECM and contain contractile filaments. They may secret erythropoietin. May have phagocytic cells that are derived from the monocyte line

72
Q

What are the interstitial cells that are found in the medulla

A

Type 1 fibroblast-like, with many lipid droplets, SER, and mitochondria with vesiscular cristae. It is the site of PG synthesis
Type II which are rounded cells with many free ribosomes and lysosomes, but no lipid dropelets. Unknown function
Type III similar to pericytes and are in the basement membrane of the vasa recta. The may act as a source of regenerative cells

73
Q

Describe the blood flow within the kidney

A

Intrarenal blood flow: 80% to outercortex, 10 to 15% to inner cortex, 5 to 10% go to medulla

74
Q

Where are the glomeruli in the kidney?

A

85% in outercortex, 15% in the inner cortex

75
Q

What parts of the kidney are most susceptible to ischemia?

A

The low flow areas. During hypovolemia, blood flow is diverted to the inner cortex

76
Q

Describe the branching of the renal arteries

A

Renal arteries –> interlobar arteries –> arcuate arteries –> interlobular arteries –> afferent arterioles (may come from intralobular arteries) –> glomerular capillary tuft –> efferent arterioles–> peritubular capillary plexus (superficial glomerulus) or vasa recta (juxtamedullary glomeruli) –> both reform the arcuate veins

77
Q

Where does the renal arteries branch into interlobar arteries?

A

Base of medullary pyramids and penetrate the medulla between renal lobes

78
Q

Describe the arcuate arteries.

A

They are division of the interlobar artiers that turn a right angle to lie at the junction of the cortex and medulla. They do not anastomose. Responsible for supplying a specific portion of the cortex

79
Q

Describe interlobular arteries

A

Arise from arcuate and penetrate cortex between medullary rays. May give rise to afferent arterioles

Renal (8 decks)

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