Histology #7 (Urinary) Flashcards
Renal Corpsucle
Marks the begining of the Nephron
- Nephron = basic functional unit of the kidney
Encompasses Bownman’s Capsule and Glamerulus
Bowman’s Capsule
A hollow sphere formed by a simple layer of squamous epithelial parietal cells
Has two poles:
Vasulure pole = Afferent and Efferent arterioles
Urinary pole = Begning of proximal convulated tubule (PCT)
Image - see shell that bowmans capsule creates for glamerulus
Afferent vs. Efferent arterioles
Afferent arterioles - ushers unfiltered blood into the glamerulus
Efferent Arteriole - Usgers filtered blood out of the glamerulus
PCT = tube that ushers filterate (filtered water) out of the glamerous (out of the nephron)
Bowman’s Capsule Histology
Bowmans capsule - circular boarder of cells that provde a base for glamerous inside
Glomeruslus
A filtration appertatus composed of fenestrated capilaries + golmerular mesengial cells + Podocytes
Three compoents:
1. Fenstarted capilaries
2. Glamerular mesengial cells
3. Pdocytes
Glomeruslus Histology
Glomerous = looks lke interweaving capialeiries (looks like tarn ball)
Fenetratsed capilaries
Function - responsible for filtering blood + creating urine + reabsorbing nutrients
Lined with fenetrated endothelial cells
- Fenetsrated = pore within the endothelial cells that allows substances to go through
Fenetratsed capilaries Histology
EM - have siluete of capilaries
***stains are hard to find
Golmerular mesengial Cells
Function - Repsonsible for turning over the basal lamina (replaces old cells with new ones) + controlling capilary diameter + sereting vasoactive compound and cytokines
Mesengial cell types prodvides structural supprt to glomerular tuft (supports ball of capilaries)
Cells are dispersed between capilary branches
Golmerular mesengial Cells Histology
See nucleus of mesengial cells
Podocytes
Overall - Unique visceral epithelial cell type
Function:
1. Provides extensive processes that completey enclose glamerular capilaries
- Preform encapsulation giving sheath to capilaries
2. Creates barriers of filtration slits
3. Maintains gloerular basement membrane
Podocytes Histology
EM - see A is complete podocyte ; B shows processes that are extension form protocyte that allow capialries to be engulfed and protexted
Golmeular filter
Golmeular filter = how we keep unwanted things out of capilaries
Composed of 3 compoenets:
1. Fenestrated epithelieum
2. Thcik badsal lamina
3. Pedicles - filtration slits between podocytes procsses
Function - stop the passage fo proteins 68kDA or larger
- 68kDa (size of albumin)
Golmeular filter Histology
See podocyte + glemalar basement membrane + endothlial + foot processes of the podocyte
Proximal conculated Tubule (PCT)
Overall - first elements where the filtrate from the renal capsule is modified
Largest section of the nephorn tubule
- Provides more opperyunity to absorb ions and molescules from the lumen
Follows a twisting conveluted path (coils in the cortext)
- When PCT enters the medulla it becomes a proximal straight tubule (Proximal straight tubules is parallel to other elements in the medula)
Epithelial cells in PCT
Epithelial cells in PCT:
1. Large
2. Eosenphilic cytoplasm
3. Forms a simple cuboidal epithelium
Proximcal conveluted tubule (PCT) histology
Becomes convuled = have different orientations (Round vs. Oval vs. straiht structures)
PCT epithelial cells = large + can’t aways see nuclei (look like they ave fewer nuclei but they don’t)
- Have esoenophilc cytoplasm
PCT epithelial cells Histology
Pink is less densly packed
See microvilli around PCT
Featires for PCT reabsorptoion
Has features on the:
1. Apical surface
2. Basolaeteral surface
3. Cytoplasm
Features for PCT reabsportion (Apical surfcae)
Apical surface has microvilli (forms brush boarder)
Has Na+-dependt co-trasnprts to imporatnt specifci molecules from the lumen into epithelial cells
- Example - absorbs all glucose + Amino Acids + Na (65% of na)
Features for PCT reabsportion (basolateral surfcae)
Has basolateral invagination
Has Na-K pumps - maintains Na and K grdainets
- ALSO has absorptive role by pumoing Na from the lumen into the iterstitial to peritubular capialries
Has chanels for molecules absorbed from the PCT lumen to exit the cells
Features for PCT reabsportion (cytoplasm)
Cytoplasm of PCT ells = has densley packed mitocondria making ATP to support Na/K pumps
PCT histology
EM - shows PCT epithelial cells (see mitocodnria + microvilli + basostatsitons)
- Basostraitoons = because of basoinvaginations
Loops of henle (overview)
First - Entering medual is the Thin decdending limb - comes from the proximal convuluted tubule
THEN as it dips it makes a 180 degre turn at the bottom
THEN becomes a thin acending limb
THEN trasnitions into the tick ascending limhb
Exits the medula back into the cortext
Loops of henle Thin dedcening limb
Function:
1. Allows water to move out of the tubule into the interstitial space
- Conatin pasive trasnports down concetration gradient - aquaporins (water moves through aquporins)
3. Concetrates filtrate
Loops of henle Thin dedcening limb Histology
Thin dcesninding is lined with simple squamous epitheliam
No Apical brush boarder
Loops of henle Thin ascending limb
Function:
1. Reabsorb Na and Cl form filtrate into the interstitial fluid through Na and Cl transporters
- Conatains passive Na and Cl chanels
- Impermable to water = diluares diltrate as it is passing through
Loops of henle Thin ascending limb Histology
Lined with simple squamous epithelum
No apical brush boarder
Image - Thin ascending and decscedning
- Left - section of thin lined with simple squamous + can see lopp
- Right - shows the thin has simple sqamous epithelium
Loops of henle thick ascending limb
Function:
1. Activley transports Na, Cl, K into interstitial fluid
- Conatins active pumps
- Impermeable to water
- Further dilates filtarte because impermebale to water
Loops of henle thick ascending limb Histology
Lined with simple Cuboidal epitheliam
No Apical Brish boarder
Uniform luminal space (disctict luminal space)
Image -
Left - lined with cuboidal
Right - Has smaller diamter than collecting ducts + uniform luminal space
Distal convaluted tubules
Follow the thick ascending limb
Have a coiled path (similar to PCT) found mainly in the corext
- Less convoluted and shorter than PCT
Intial segment lies next to the corpsucle and forms the juxtagolmerular appuratus
Distal convaluted tubules Histology
Always occupy less space than PCT
- DCT epithelial cells are smaller than PCT epithelial cells
- Tall + simple cudoidal epitheluum
In any given sectio of kidney the corext - less space is distal convaluted tube compared to prximal tube
Distal convaluted tubules function
Overall function - fine tuning of Na reapsoption (<5%)
Apical surface - Na-dependent co-trasnporters and Na chanels (imports Na from lumen into epithelial cells)
Basolateral surface - Na/K pumps (transports Na from the fitrate (urine) in lumen into the interstitium)
Cytoplasm - densly packed mitocondria
Distal convaluted tubules Histology (EM)
Shows DCT epithelialc ells + shows apical microvilli + basoinvagination + packed eloggated mitcondira
Summary of beinging Loop of henley histology
Collecting Duct
Location - Cortext and the medulla of the kdiney
Several collecting tubules –> leads to one collecting duct in corext –> leads to medullary collecting duct
Composed of simple cubodial epithelial cells –> then have columnar epithelial cells
- Simple cuboidal cells = helps fluid reabsorption of Na and water
- Columnar = helps mainati acid base homoestasis (secrets acids or bases depending on pH needed)
Histology - stain pale with distict boarder of the cells
Function - site for fluid reabsorption and acid-base balance
Uriter
Layers:
1. Urothelieum (innermost)- stratofied epithlieum with multinucleated cells
2. Lamina propria - connective tissue
3. Muscularis - smooth muscle and connective tissue
- Have 2 layers –> arranged in 2-3 layers of longitudal and circular layers
- Smooth muscle contracts to push fluid
- Closer to the bladder is longitudnal layer = does parastlysis to move urine to the bladder)
4. Adventitia - loose connective tissue
Uriter
Left - Urithelium is at the top –> has umbrella cells + bi/multinucleated cells)
- Sits on top of lamina propina
- Lamina propria sites on top of Muscaris
- Muscalris = can see longitunal on tomm of circulare)
- See adnevtitia after muscularis
Macula Densa Cells
Abdunece of epithelial cells located in the juxtaglomerular apparatus
Function - Responds when NaCl concetration is out of standrad range (gulates NaCl concetration)
Juztaglomerular Apparatus (JGA)
Functional Unit in the nephron
- Location - in vasular pole
- Junction of the glemerous and afferernt and effecter arterials
Function - Tubuloglamerlar feedback system conrtols renal blood flow
- Controls glemalular filtration rate (GFR) by sneinsg amount fluid in ascending limb
- Tubular control of renin section - has role in startng angiostestin-aldostrone system
Juztaglomerular Apparatus (JGA) Components
JGA has 3 cell types:
1. Macula densa cells - thick yellow layer
- Thick layer of cells in bottom of distal tubule (on glamerular side)
2. Juxtaglomerular cells (granular cells)
3. Extraglomerular mesangial cells (lacis cells)
Macula densa cells
Dense spot in the thick ascending limb
Monotor NaCl concetration in filtarte through membrane trasnporters
Signals to speed up or slow down to change concetration:
- When concetation is too high –> slow down filtraton GFR (signlals affertent arterioles to constroct through adenosine which causes constriction)
- When concetration is too Low –> speed up the filtration GFR so less solute is oulled out (signal juxtaglomerular cells to release renin –> get angiogenstin) –> angiogenstin causes arterioles to constict + other systemic effects of angiotenisin
Images - circled - dense cells in circle on glomeular cells
Juxtaglomerular cells (granilar cells)
Location - tunica media of afferent arteriole at entrance to glomeruli(build around affernt aretrioeles ; localize to tunica media)
- Image - blue cell around edge of afferent arteriol ; tunica media is on side
Modified smooth muscle cells
Function - Produce + store + secrete renin
Senses blood pressure in aretiole through bacorecptors - increased BP –> secretes renin
- Have dark vacule filled with renin
Responds to signal from from macula densa cells + sympathetic nervous system (highly innervated)
EM image AA and G is in the dark layer of cells around both side of granial cells
How do Juxtaglomerular cells secrete renin
Sercet renin through own barrow receptors + from siglas in sena + nerve fibers
Extraglomereular Mesangial cells (lacis cells)
Location - Within prymid juncton between afferent and eferent arteriole and macula densa
- purple cells in middle of junction
Modified smooth muscle
Function - Not fully known
- Possible involovment i stimulating renin secresyon
- Remove trapped residue/deris from the glomerular basment membrane
Image -
H/E - block arrow shows prydimd
EM - see afferent and effernet - Extraglomereular Mesangial cells are between them
Renin and Blood Pressure Homeostasis
Renin = enzyme produced by Juxtraglomerular cells
Regulates blood pressre via renin-angiostensin - aldostrone system (RAAS)
- Maintains BP homoestsis
- Low BP = helps increase BP by starting angiogenstin-aldostrine system)
Release inhibited by arterial natruitic peptide (ANP) from stretched atria in heart in repsonse to increase in blood pressure
Juxtaglomerular apparatus and blood pressure control
Produced by Jaxtaglomerula cells in repsonse to:
1. Low BP (hpotension)/reduced extracellular fluid
- Detected by barorecptores in the afferent arteriole
2. Low NaCl concetration (Hypoantremia)
- Detected by macula dense cells the distal convoluted tubule
3. Sympathetic nervous sytem activation
- Beta-1 Adregenic recptors on JG cells
Renin-Angiogenstin-Aldosrtone System
Renin is made –> Renin is released for the kidney –> converts angiogenstin (made in the liver) to angiogenstin 1 –> angiostine 1 is converted to angiogenstin 2 by angiogenstin convertying enzyme (ACE) –> angiogenstin 2 is the main effector of the system
Effect of Angiogenstin 2
Angiogenstin 2 –> hormone that has widepsread effect to raise BP and blood volume
Effects:
1. Acts on arterilals –> causes constriction = increase BP
2. Acts o kidney = increase na absorption
3. Acts on adremal gland
4. Acts on cortext –> increase secertion of aldostrone = affects Na Absorption
5. Increases ADH = increases thrist = increase blood volume + increases water reabsprotion
Renin-Angiogenstin Aldostrine system (overall)
Extrarenal collcting system
Extrarenal collcting system = Urters + bladder + urithra
NOW there is no reabsportion = have the urothelial –> urotheliuam has chemcial restsince + is reststent to stretching
Urothelium
Urine is toxic waste
Urothelium - specialized proetxtive epitheliual cells
- Chemical restince
- Prevent leaskge even when stretchs
Layers of Urothelium:
1. Superfical umbrella cells (outter)
2. Intermiate cells
3. basal Cell layer (bottom)
Other tissue layers (below the urothelium) -
Lamina propria
mascularis
Adventia
Urothelium - Umbrella cells
Most apical layer of cells (single layer)
- Top layer in Image
Often Binucleated
Width can range from 25-250 um long
Specialized disk shaped vesciles
Urothelium - Umbrella cells Histology
See relaxed vs stretched –> can do this because of discoidal vesicles
- See discoidal vesicles on EM (discoid vesicles = also called fusiform vesicles)
Urothelium - Umbrella cells Histology #2
See how expandsion and contraction occurs as cell stretches
Urothelium in Urinary Bladder
Urothelum is >6 cells thick
Thin cubmucosa
Mucsularis - has a extra 3rd circular layer (dentrusor)
Superior portion of the adventitia is mesothelium
Image
- H/E - see three layers of mucularis –> change orientation in each layer
Urothelium in Urinary Bladder histology #2
Urothelium (urethra)
Includes a 3rd layer of muscle (3rd layer is skelatal muscle) (External Urinary sphicter)
Has Skeltal muscle in proximal part of urtehra (because volentary action)
Along its length its transitions from urothelieum to psudostratified columnar to non-keritinized startified squamous
- Chnages from urethelium to standrad epithelum and will be continus with skin
Urothelium (urethra) transition
Urothlium transitions along the urethra
Histology - Logitudnal section of fossa Navicularis
- See trasnition of Psuodstratified columanr to statified squamous
Chronic kidney disease (overall)
Overall - Damage to the kidney - can’t prefrom their function (Ex. no filtration)
- Main function of kidney = filtered blood = gets rid of waste + excess fluid
Chronis and progressive - occurs slowley over a long period (has multiple stages)
- Last stage = kidney failure = kidney is not functioning = can’t get rid of waste = have buldup of waste = many side effects
Result - leads to a build up of waste in body
How do you test kidney function
Test kidney function with GFR (Glamerular filtraton rate)
Low GFR = have issues with kidneys - IF continues = can lead to CKD
CKD causes and symptoms
Caused by many things:
1. Age
2. Obesity
3. Family histpry
4. Diabetes - main cause
5. Hypertention - main cause
Have many symptoms (many are unrealted to kidney)
1. Puffy eye
2. Issue sleeping
Treatment - dialysis + kidney transplant in late stage kidney failure
Diabetes
Diabetes - chronic condiation charcterized by high blood glucose levels due to insufficet insulin production or use
Acute vs. Chronic failure
Causes of chronic kideny disease
- Diabetes
- Hypertension
BOTH can cause chronic kidney failure
Diabetes
Inaqdeuwate insulin or insulin s not working properly –> leads to high glucose –> leads to thicking of vessles and damage of nephron + lose protein in urine
Diabetic Nephropathy
Symptomes:
Blood vessel damage - high blood glucose causes the vessels of the kidney to become narrow and clogged
Nephrone damage - thicken and scaring causing proteniuria
Nerve damage - Bladder can’t signal to the brain when full –> high pressure damages the kidneys (damage kidneys because have backup)
Increased risk factors of diebetic nueropathy - smokeing + poor diabetes managment + high salt diet
Treatment - manage disease progression by managing diabetes
Diabetic Nephropathy Glemerular basement membane thcikening
A - Healthy basment membrane (thin)
B - Diabettic - basement membrane is thicker
- Hypoglycosylation end product buildup = thickens basment membrane = not getting filtration = have protenueria (loss of protein ; maily albumin)
First sign of diabetic nueropathy (early stage)
Diabetic nueropathy histological signs
Diabetic nueropathy histological signs:
1.Glemerular basement membane thcikening
2. Mesangial expasnion
3. Nodular Scelrosis
4. Global Glameruloscelrosis
Diabetic Nephropathy Mesangial expasnion
Diabetic - cells increase in area + there are more of them + more ECM = dagamge kidney strcuture = damage function = get protoneuria
Diabetic Nephropathy Nodular Scelrosis
Nodule scelrosis = lesions (big circles) - main indictaor of diabetic related CDK (point of no retrun)
Main marker looked for
Diabetic Nephropathy Global Glomeruloscerlsois
Hardening and scaring of the gloemerus (blood vessels are impared)
- No filtration
- Cause by hyperglycemmia
- No Kidney function
- Need Dialysis
Hypertension
Blood pressure is blood vessles in consisteny too high (130/80)
- Second stage hypernetsion = higher than 140/90
Second leading cause of kidney failure in US
Danrous cycle of hypertension–> kidney function inhibition –> more hypertension
- Hypertension causes Blood vessels to constrict = inhibits kideny function = kidney can’t extret water and ions = leads to more hypertenstion because can’t reasborb water and ions
Image - see can cause thickening of Blood vessels
Hypertesnion pharmacologicla treatments
Overall - use Indiction of diuresis and vasodilation
Main goal of treatments = induce diureses to release pressure in Blood vessels or do vasodialtion
Chart = shows meds:
1. ACE inhibitors
2. AABrs - act on angiotenstin system
3. Alpha and Beta blockers - act on cardiac muscle to induce vasodilation
Diuretics
Mechanismof action - increase urine production by infleunceing the kidney to exrete extra water and sodium to releive Blood pressure and Blood vessels
Sveral classes of diuretics exist with varing efficac and act on various parts of the kidney nephron unit
Classes of Diuretics
- Carbonic anhydrase inhibitors - increase bicarbinate + Na + Cl extretion in PCT
- Loop diuretics - inhibit Na/K/2Cl co-trasnprter and Na reabsorption in the loop of henle
- Affect thick ascending limb - Thriazide - inhibits Na/Cl co-trasnporter in DCT and reabsoprtion of Na
- Affecst distal convluted tube
- K Sparing - Aldostrone receptor antagpnist (inhibits synthessis of Na cganges = lose Na absprtion function) + EnaC blocker (inhibits influs of Na in collecting ducts)–> BOTH act on the collecting duct ENaC chanels
Issues with diuretics
Different drugs have different eficacey
- If inhibit eralier – then neprhone will try and compenstae later
Diuretics have many side effects –> can lead to low K because kidney is trying to get more Na t the end of the nephron = pushes K out
Renin inhibitors
Mechansim of action - Bind to active site of renin molecule to prevent it from binding to angiotensinogen and the subsequent conversion of angiogenstin 1 to angiogenstin 2
- Inhibits the whole pathway
NOT used as primary pharmocologic treatment because has many side effects
Nephrotic syndrome Manifistations
Nephrotic syndrome = group of syndromes that indicate the kideny is not functioning
Has 4 manifestaions that indictae disrupted functioning of the kidneys (stem from increase permeability in glaemrus)
1. Protenieura
2. hypoalbumimia
3. Hyperlipidemia
4. Edema
Symptims - swelling + foamy urine + weight gain + loss of apetite
Complications - Infection + blod clots + hypertension + diffuclty breathing + Chronic kidney disease
Nephrotic syndrome cause
Caused by increase permeability of glomeruli due to kidney disease or systemic diseases
Normal galmeular barrier = has 3 layers (fenstarted epithelium –> Basement Membrane –> protocytes)
- Protocytes prevent protein from going from the blood into the urine)
Nephrotic = protocytes are affected = lose structural integrity = proteins go across glamerous filtration barrier
Caused by disease that affects proteocytes = kidney diseases or systemic diseases
Nephrotic syndrome Proteinuria and Hypoalbuminemia
Proteinuria - increase in protein in urine
- Layer of protcytes is affected = proteins go through filtration barrier = extrte protein in urine
Hypoalminemia - decrease in albumin in blood
- Decrease albumin = decrease in oncotic pressure
- Lose albumine in urine = low levels of albumin in blood
Nephrotic syndrome edema
Have Hypoalbiinmeria (decrease in albuine) –> leads to swelling due to fluid accumilation
Albumin = important in oncotic pressure –> low albumin = lower oncotic pressure = less fluid goes into capilaries AND excess fluid in interstitial space/tissue = causes edma
Nephrotic syndrome Hyperlipidemia
Hypoalbimineria = decrease in albumin in blood –> leads to hyperlipidemia –> leads to increase in cholerstal and fats in blood
Liver tries to compensate for increase of protein blood = makes lipoproteins + cholertral + albumin = can lead to higher lipids
Nephrotic syndrome Histology
Histology depends on disease causing nephrotic syndrome
Left - Focal (kideny disease) = hardening of glamerular capilaries
- Only sgeemnts of gemeular
Right - AB deposition in glemaeular capilaries
Kidney that causes neropathy = causes layer of protocytes in glamelular filtration layer
