SUGER (summary sheets) Flashcards
Where does normal proliferation of the skin occur?
Just in the basal layer
What are the 6 functions of the skin?
- Barrier to infection
- Thermoregulation
- Protection against trauma
- Vitamin D synthesis
- Regulate water loss
What are the basic layers of the skin?
- Epidermis
- Dermis
- Subcutaneous tissue
What is the outermost layer of the epidermis?
The stratum corneum
Where are corneo-desmosomes and desmosomes found in the skin?
Epidermis
What is the function of corneo-desmosomes (adhesion molecules)?
Keep the corneocytes together
When are there an increased number of corneodesmosomes in the epidermis?
In diseases such as psoriasis when there is a thickening of the stratum corneum
When are there an decreased number of corneodesmosomes in the epidermis?
In diseases such as atopic eczema when there is a thinning of the stratum corneum - meaning an increased risk of inflammation
What is the function of filaggrin?
Produces natural moisturising factor (NMF)
Where is filaggrin derived from?
From profilaggrin
What is profilaggrin?
A structural component of the cornfield envelope
How is the skins hydration maintained?
With the corneocytes being filled with NMF, which keeps water inside the skin
What is an important role of NMF?
Helps maintain an acidic environment at the outer surface of the stratum corneum
What is desquamation in skin and why is it done?
- The shedding of mature corneocytes from the surface of the stratum corneum
- In order to balance the introduction of new cells in the basal layer of the epidermis
How does the desquamation of the skin happen?
Involves the degradation of the extracellular corneo-desmosomes under the action of proteases
What is the normal pH of the skin and why is this maintained?
- pH 5.5
- Allows proteases to remain on the skin, thereby enabling the balance of new cells from the basal layers
What is the function of the lipid lamellae of the skin?
Keeps water inside the skin cells
What makes irritants and allergens ‘bounce’ off the skin?
The presence of the lipid lamellae
In the skin, what acts as an efficient barrier to the penetration of irritants and allergens?
The normal & intact stratum corneum
In the skin, which barrier prevents against water loss?
The normal & intact stratum corneum
What is the brick wall model of the skin?
- Corneocytes are bricks
- The corneodesmosomes are iron rods
- The lipid lamellae is the cement
What is the role of vitamin D in the skin?
Essential in producing the anti-microbial peptides necessary to defend the skin from bacteria and viruses
What do irritants do to the skin?
Breaks down healthy skin
What do allergens do to the skin?
Trigger skin flare ups by penetrating into the skin and causing the skin to react
What are all skin flareups caused by?
Allergens which are able to penetrate into the skin, where they are met with lymphocytes which release chemicals which induce inflammation
What does red skin mean?
Dilation of blood vessels - due to lymphocyte activity
What does itchy skin mean?
Stimulation of nerves
What does dry skin mean?
Skin cells leaking - due to lymphocyte activity
What is the effect of increased pH on skin?
Results in damage to the skin barrier since the corneodesmosomes be come damaged by the increased pH resulting in the breakdown of the skin barrier and thus increasing the risk of infection
What causes a lack of water retention in the corneocytes?
- Lack of presence of profilaggrin and consequentially filaggrin
- Means a lack of NMF so less water retention
- Causes a pH increase
What happens to the stratum corneum in acne?
Hypercornification of the stratum corneum - results in adherent cells blocking the entrance to hair follicles
After the blocking of hair follicles in the skin, what causes acne?
- Increased production of sebum by sebaceous glands (greasy skin)
- Some sebum becomes trapped in the narrow hair follicle
- The sebum stagnates in the pit of the follicle with no oxygen
- Provides anaerobic conditions which allow the propionic bacteria acnes to multiply
- They break down triglycerides into free FA, resulting in irritation, inflammation ad attraction of neutrophils
- Results in plug formation and further inflammation as the follicles is filled with neutrophils
What is cosmetically induced acne?
Acne caused by cosmetics - as they can plug the hair follicle and initiate the process
Where do the kidneys lie in the body?
- Retroperitoneal
- Between T12-L3
Where are the kidneys derived from embryologically?
The mesoderm
Why is the right kidney lower than the left?
Since it is pushed down by the liver
Where is the hilum of the right kidney?
L2
Where is the hilium of the left kidney?
L1 (transpyloric plane)
What are the 3 distinct structures of the kidney (from outside in)?
Cortex, medulla and pelvis
How thick should the cortex of the kidneys be in a healthy adult?
7mm
What does the renal medulla consist of?
20 upside down pyramids
What does the renal pelvis contain?
Fat & urine collecting system
What is the urine collecting system lined by?
Transitional epithelium
What is the cortex of the kidney compromised of?
- Renal corpuscles (Glomerulus & Bowman’s capsule)
- The proximal & distal convoluted tubules
What is the medullary ray?
A collection of loop of Henle tubules and collecting ducts that originate from the nephrons which have their renal corpuscles in the outer part of the cortex
Where is the medullary ray found?
The renal cortex
What is the function of the loop of Henle tubules?
They concentrate urine using a countercurrent multiplier system
What gives the cortex its striated appearance?
The medullary rays
Does the medulla have any renal corpuscles?
No
How are the tubules of the medulla of the kidney orientated?
Radially, pointing from the cortex to the medulla
Are there are glomeruli in the medulla of the kidney?
No - just tubes and blood vessels
What are the tubular structures of the medulla of the kidney?
- Tubules of the loop of Henle
- Tubules of the collecting duct
- Blood vessels
What is the space that the urine drains into?
The pelvis
What structures is the renal pelvis continuous with?
- The collecting ducts proximally
- The ureters distally
What is the renal pelvis lined with?
Transitional epithelium
Where do the tips of the medullary pyramids project into?
The renal pelvis - at this point the pyramids are composed purely of collecting ducts
Where does the renal artery come off the abdominal aorta?
At the level of L1
How does the renal artery divide?
Into segmental arteries which then lead to a radial network of arcuate arteries
Where do the arcuate arteries travel in the kidneys?
Around at the junction between the cortex and medulla, and then give off interlobar arteries
Where do interlobar arteries supply?
Each lobe of the kidney (a medullary pyramid and the overlying cortex)
How do the interlobar arteries divide?
To form the interlobular arteries which then terminate in the form of the afferent arterioles
What is the venous system of the kidney?
Mirrors that of the arterial system
What is the divisions of the arteries in the kidney?
- Abdominal
- Renal
- Segmental
- Arcuate
- Interlobar
- Interlobular
- Afferent arterioles
How many nephrons are there in the cortex and medulla?
Millions
What structures of the nephron are in the cortex of the kidney?
- The proximal & distal convoluted tubules
- The renal corpuscles (consists of the Glomerulus & Bowman’s capsule)
What structures of the nephron are found in the medulla of the kidney?
- Loop of Henle and collecting ducts
What structures of the nephron are found in the pelvis of the kidney?
Receives the collecting ducts
What are the 5 distinct segments of the nephrons?
- Renal corpuscle
- Proximal convoluted tubule
- Loop of Henle
- Distal convoluted tubule
- Collecting duct
What is the function of the renal corpuscle?
The filter
What is the function of the proximal convoluted tubule?
For reabsorbing solutes
What is the function of the loop of Henle?
For concentrating urine
What is the function of the distal convoluted tubule?
For reabsorbing more water and solutes
What is the function of the collecting duct?
For reabsorbing water and controlling acid base & ion balance
What does the renal corpuscle consist of?
- The glomerular tuft and Bowmans capsule
- A tuft of convoluted tubules with fenestrated walls
What is the glomerular tuft supported by?
Smooth muscle mesengial cells
What is just outside of the glomerular capillaries?
A basement membrane
What is next to the basement membrane of the capillaries?
- A layer of podocytes
What is the structure of the glomerular basement membrane?
A fusion of 2 basement membranes - the capillary basement membrane and the podocyte basement membrane
What is the most proximal point in the urinary tract?
The Bowman’s capsule
What are most of the seen cells of the glomerulus?
The mesangial cells and capillary endothelial cells
How can mesangial cells be differentiated from the capillaries?
The tissue can be stained with PAS
What does PAS stain in the kidney?
The glycoproteins in the glomerulus basement membrane - highlighting capillaries and allowing you to see the mesangial cells in-between
What is the structure of mesangial cells?
Modified smooth muscles
What are the 3 main functions of the mesangial cells?
- Structural support for the capillary and production of the extracellular matrix
- Contraction of these cells tightens capillaries and reduces GFR (important for tubuloglomerular feedback)
- Involved in the phagocytosis of membrane breakdown products
What are the two components of the juxtaglomerular apparatus?
Afferent arteriole and distal convoluted tubule
What cells is the endothelium of the afferent arteriole expanded to form?
Granular cells
What are the functions of granular cells?
Able to detect blood pressure - secrete renin in response to a reduction in blood pressure
Where is the distal convoluted tubule closely aligned to?
Te glomerulus and afferent arteriole
What is the macula densa and what is its function?
An expansion of cells at the juxtagolmerular apparatus of the distal convoluted tubule which is capable of detecting sodium levels
What happens in terms of sodium when filtration is slow in the kidneys and what can be done to combat this?
- Slow filtration means more sodium with be absorbed
- Macula densa will send a signal to reduce the afferent arteriole resistance
- Increase glomerular filtration
Name another cell type which are present in the juxtaglomerular apparatus?
Lacis cells
What epithelium does the proximal convoluted tubule have?
Cuboidal epithelium
What do the cells of the proximal convoluted tubule have and why?
- Have microvilli to increase SA
- This increased the absorptive capacity of the cell
Why do the cells of the proximal convoluted tubule have lots of mitochondria?
- They actively transport ions from the glomerular filtrate (including 2/3 of the sodium and potassium)
What is reabsorbed at the proximal convoluted tubule?
NaCl, proteins, polypeptides, amino acids and glucose
What else does the proximal convoluted tubule sometimes absorb?
The small protein molecules that got through the glomerulus
What is the function of the lysosomes of the proximal convoluted tubule?
- Involved in the degradation of small protein molecules that are reabsorbed from the urinary space
Which has more lysosomes: the proximal or distal convoluted tubule?
Proximal
What is the gross structure of the loop of Henle?
- Has descending and ascending limbs
- Both with thin and thick segments
What is the epithelium of the thin segments of the loop of Henle?
Simple squamous epithelium
What is the epithelium of the thick segments of the loop of Henle?
Low cuboidal
What blood vessel is the loop of Henle supplied by?
Rich vasa recta
Where does each loop of the loop of Henle dip to?
Down far into the medulla and then returns from the distal convoluted tubule to return to the same nephron it left
What passively flows out of the thin descending limb of the loop of Henle ?
Water (NOT ions) - this concentrates the urine
What is actively pumped out the ascending limb of the loop of Henle?
The ions that the body wants back
Are the vasa recta far from the glomerulus?
Yes
Where does the afferent arteriole enter in the kidney to supply oxygen?
Into the glomerulus
What is the loop of Henle prone to?
Ischaemia - temporary loss of blood supply/inadequate blood supply
How can the proximal and distal convoluted tubule be differentiated?
- The DCT doesn’t have microvilli
- The DCT is much shorter
What are the structure of the cells of the distal convoluted tubule?
- Cuboidal
- Contain mitochondria
How is the distal convoluted tubule involved in regulating acid base balance?
Acts to acidify the urine by secreting hydrogen ion into it (derived from intracellular carbonic anhydrase)
What is hypernatraemia?
High Na+
What is hypokalaemia?
Low K+
What exchange does the cells of the distal convoluted tubule do?
- Exchanges urinary Na for body K
- This effect is mediated by aldosterone
What epithelium is present in the collecting duct?
Cuboidal
What are the two cell types of the collecting duct?
Principle cells and intercalated cells
What is the function of the principle cells in the collecting duct?
- Respond to aldosterone (exchanging Na for K)
- Respond to ADH (increasing water reabsorption by insertion of aquaporin-2 into the apical membrane of the cell)
What is aquaporin-2?
Membrane channel for water reabsorption in the collecting duct
What is the function of intercalated cells in the collecting duct?
Responsible for exchanging acid for base
What do alpha intercalated cells secrete?
Acid
What do beta intercalated cells secrete?
Bicarbonate
How can the collecting duct be differentiated from the loop of Henle?
- Has plumper epithelium
- A round central nuclei
What is the structure of transitional epithelium (urothelium)?
Multilayered/stratified epithelium that is able to stretch in three dimensions meaning that the volume of the cells stay the same but the thickness and area they cover changes
What is the function of the renal pelvis?
- Transmits filtrate from nephron to the ureters
- Collecting duct drains into he pelvis
What does the surface layer of the urothelium contain?
- Umbrella cells (large and cover several underlying intermediate cells)
- Have tight junctions at their surface - to prevent urine getting in-between cells
What are the three layers of the bladder epithelium?
Surface, intermediate and basal
What cells does the basal layer of the bladder epithelium consist of?
Cuboidal cells
What is the epithelium of the ureters?
Transitional epithelium
What is the muscular tube structure of the ureter?
- Spiral muscular tube
- Inner (longitudinal)
- Outer (circular)
Do the ureters have serosa?
Yes
How is urine propelled along the ureter?
By peristalsis
What is the adventitia in the ureters?
Loose
What is the epithelium of the bladder?
Transitional
What are the layers of the bladder?
- Lamina propria
- Muscularis mucosa
- Submucosa
- Muscularis propria
- Subserosa & serosa
What prevents reflux into the ureter form the bladder?
The functional valve
What is the epithelium of the urethra?
Transitional
How many sphincters are there in the urethra?
2
What is the structure of the internal sphincter of the urethra?
Smooth muscle from the bladder
What is the structure of the external sphincter of the urethra?
Skeletal muscle from the pelvic floor
How long is the female urethra?
4-5cm
What is the proximal epithelium of the female urethra?
Transitional
What is the distal epithelium of the female urethra?
Squamous
How long is the male urethra?
20cm
What are the 3 parts of the urethra in males?
- Prostatic urethra
- Membranous urethra (transitional epithelium)
- Penile urethra (pseudostratified epithelium proximally & stratified squamous epithelium distally)
What are the 3 major functions of the kidneys?
- Endocrine function (secreting hormones)
- Maintain balance of salt, water and pH
- Excrete waste products
What percent of the cardiac output does each kidney receive?
20%
What is the total renal blood flow of both kidneys?
1L/min
What is the total urine flow of the kidneys?
1ml/min
What are the 9 divisions of the renal artery?
- Renal artery
- Segmental artery
- Interlobar artery
- Arcuate artery
- Interlobular artery
- Afferent arteriole
- (Nephron) - Glomerular capillary
- Efferent arteriole
- (Nephron) - Peritubular capillary
How many capillary beds does each nephron have and where are they located?
- 2
- One at the glomerulus
- One at the peritubular area
How many sets of capillaries are there within the nephron and what are they?
- The glomerular capillaries (glomeruli)
- The peritubular capillaries
- Connected to each other by an efferent arteriole (how the blood leaves the glomerulus)
How many sets of arterioles and capillaries does the renal circulation have?
Two of each
What do the peritubular capillaries do after supplying the tubules with blood?
- Join to form the veins by which blood leaves the kidneys
- The entire kidney is covered by podocytes
- Many tubular processed are active so require a blood supply
What is the renal corpuscle?
The whole unit of the glomerular tuft and Bowman’s capsule
What is the function of the renal corpuscle?
Forms a filtrate from the blood that is free of cells, larger polypeptides and proteins
What happens to the filtrate formed in the renal corpuscle?
- Leaves the renal corpuscle and enters the tubule
- As it flows through, substances are added or removed
- The fluid remaining at the end of each nephron combines in the collecting ducts and exits the kidneys as urine
What is the glomerulus?
A compact tuft of interconnected capillary loops
What is the blood supply of the glomerulus?
The afferent arteriole
What does the glomerulus protrude into?
Fluid-Filled capsules (Bowman’s capsule)
How much of the plasma filters into the Bowman’s capsule as the blood flows through the glomerulus and where does the rest filter?
- About 20%
- By the efferent arteriole
What epithelium is the Bowman’s capsule covered in?
Parietal epithelium
What is Bowman’s space?
A fluid-filled space which is present within the capsule
What is the function of Bowman’s space?
The filtrate from the glomerulus collects here before flowing to the proximal convoluted tubule
How is the blood in the glomerulus separated from the fluid in Bowman’s space ?
- By a filtration barrier of 3 layers
- Single-celled capillary endothelium
- Basement membrane (also referred to as the basal lamina)
- Single-celled epithelial lining of Bowman’s capsule (podocytes)
What is the function of podocytes?
They have an octopus like structure in that they possess a large number of extensions or foot processes which acts as the glomerular filtration barrier
How does fluid filter in Bowman’s capsule?
- First, across the endothelial cells
- Basement membrane
- Between the foot processes of the podocytes
Where do efferent arterioles carry blood?
- Away from the glomerulus
- Then supply the peritubular capillaries which supply the proximal and distal convoluted tubules
- Also supply the vasa recti which supply the loop of Henle
What is the blood supply to the loop of Henle?
The vasa recta
What do both the peritubular capillaries and the vasa recti supply?
- Water & solutes to be secreted into the filtrate
- Blood to carry away water & solutes reabsorbed by the kidneys
What is the longest and most coiled tubule of the kidney?
- The proximal convoluted tubule
What is the cellular structure of the proximal convoluted tubule?
Simple cuboidal brush border
What is the segment of the tubule of the kidney that drains the Bowman’s capsule?
- The proximal tubule
- Consists of the proximal convoluted tubule and the proximal straight tubule
What is the structure of the loop of Henle?
- A sharp, hairpin like loops consisting of a descending limb coming from the proximal tubule
- Also has an ascending limb leading to the next tubular segment, the distal convoluted tubule
What is the epithelium of the distal convoluted tubule?
Cuboidal epithelium with minimal microvilli
Where does fluid flow from the distal convoluted tubule?
- Into the collecting-duct system, which is comprised of
- The cortical collecting duct
- The medullary collecting duct
Until what point are the nephrons completely separate?
The merging of the cortical collecting ducts
What happens after the cortical collecting ducts merge?
- There is additional merging to form the large medullary collecting ducts
- These drain urine into the renal pelvis (kidney’s central cavity)
What is the renal pelvis continuous with?
The ureter draining that kidney
Where is all the renal corpuscles contained?
The renal cortex
Where does the loop of Henle extend from?
The cortex - varying distances down into the medulla
Where do the medullary collecting ducts pass through?
The medulla on their way to the renal pelvis
What are the tubules in the cortex surrounded by?
Peritubular capillaries
What are the two types of nephron?
Juxtamedullary and cortical
What is a juxtamedullary nephron?
The renal corpuscle lies in the part of the cortex closest to the cortical-medullary junction
What is significant about the loop of Henle of a juxtamedullary nephron?
- They plunge deep into the medulla and are responsible for generating an osmotic gradient in the medulla that is responsible for the reabsorption of water
- They have vasa recta in close proximity
What is a cortical nephron?
Their renal corpuscles lie in the outer cortex and their loop of Henle don’t penetrate deep into the medulla
What is the function of the cortical nephrons?
They are involved in reabsorption and secretion but don’t contribute to the hypertonic medullary interstitium
What is the juxtaglomerular apparatus and where is it found?
- The macula densa (a patch of cells in the wall of the ascending limb as it becomes the DCT)
- The granular cells (juxtaglomerular cells) (at the wall of the afferent arteriole)
What is the function of the granular cells of the kidney?
Secrete renin into the blood (initiating RAAS)
What is the function of the macula densa of the kidney?
Detect how much NaCl is passing through the DCT and sends signals to the granular cells to produce renin
What is glomerular filtration?
The passage of fluid from the blood into Bowman’s space to from the filtrate
What is the distal part of the nephron responsible for?
Secretion and reabsorption
Where does the glomerular filtrate flow through?
- Glomerular capsule
- Proximal convoluted tubule - Nephron loop
- Distal convoluted tubule
- Collecting duct
- Papillary duct
- Minor calyx
- Major calyx
- Renal pelvis
- Ureter
- Urinary bladder
- Urethra
Where does urine formation begin?
With glomerular filtration
What are the components of glomerular filtrate?
- It is cell free contains virtually all substances in same conc. as plasma (except larger proteins)
- The exception to this is things which are bound to plasma proteins, so can’t get filter e.g. Calcium
How is the filtrate of the nephrons altered during passage through the tubules?
Altered by the movement of the substances from the tubules to the peritubular capillaries and vice versa
What is tubular reabsorption of the kidney?
When the direction of movement is from the tubular lumen to peritubular capillary plasma
What is tubular secretion of the kidney?
When the direction of movement is from the peritubular capillary plasma to the tubular lumen
Which molecules can pass freely through the filtration barrier of the kidney?
- Small molecules & ions
- Examples include glucose, uric acid, potassium and creatine
How are negatively charged anions, such as albumin, repelled from the filtration barrier of the kidney?
Fixed negative charge in the glomerular basement membrane repels negatively charged anions
Why can’t albumin pass the filtration barrier of the kidney?
- Having a heavy molecular weight
- It is negatively charged
What is significant about the initial filtrate of the kidney?
It is protein free
What is the only protein which is usually found in the urine?
Uromodulin - it is produced by the thick ascending limb of the loop of Henle
What determines the crossing of the filtration barrier of the kidney?
- Pressure
- Size of molecule
- Charge of molecule
- Rate of blood flow
- Binding to plasma proteins
What is the charge of the basement membrane of the filtration barrier of the kidney?
Negative
How does pressure determines the crossing of the filtration barrier of the kidney?
- Determines glomerular filtration
What happens to the hydrostatic pressure along the length of the glomerular capillary?
It is constant
Does the Bowman’s capsule provide oncotic pressure?
No - as there are no proteins
What happens to oncotic pressure as you go along the glomerular capillary?
Increases as proteins get more concentrated
Define glomerular filtration rate
The volume of fluid filtered from the glomeruli into Bowman’s space per unit time (mins)
What is the equation for GFR?
- GFR = KF(PGC - PBS - piGC)
- KF = The product of the permeability of the filtration barrier and the surface area available for filtration
- PGC = Glomerular capillary hydrostatic pressure
- PBS = Bowman’s space hydrostatic pressure
- piGC = Osmotic/oncotic pressure of the glomerular capillary
- piBS = Osmotic/oncotic pressure of Bowman’s space
Does the glomerular capillary hydrostatic pressure favour or oppose filtration?
Favours
Does the Bowman’s space hydrostatic pressure favour or oppose filtration?
Opposes
Does the osmotic/oncotic pressure of the glomerular capillary favour or oppose filtration?
Opposes
What is the filtration coefficient?
The product of the permeability of the filtration barrier and the surface area available for filtration
What is GFR determined by?
- Net filtration pressure
- Permeability of the corpuscular membranes
- Surface area available for filtration
What is the GFR directly proportional to at any given net filtration pressure?
The membrane permeability and surface area
How is the GFR physiologically regulated?
By neural and hormonal input to the afferent and efferent arterioles, which cause changes in net glomerular filtration pressure
How are the glomerular capillaries unique?
They are situated between two sets of arterioles (afferent & efferent)
What do constricting afferent arterioles do to hydrostatic pressure in the glomerular capillaries?
Decreases - similar to arteriolar constriction in other organs and is due to a greater loss of pressure between arteries and capillaries
What does constricting afferent arterioles do to the GFR?
Decreases it
What do constricting efferent arterioles do to hydrostatic pressure in the glomerular capillaries?
Increases - Due to them lying beyond the glomerulus
What does constricting efferent arterioles do to the GFR?
Increases it
What does dilating afferent arterioles do to the GFR?
Increases PGC, so increases the GFR
What does dilating efferent arterioles do to the GFR?
Decreases PGC, so decreases the GFR
How can GFR be measured?
By measuring excretion of a marker substance
What must the marker substance which is used to measure GFR be?
- Freely filtered (same conc. in blood and tubular fluid)
- Not secreted or absorbed in the tubules
- Not metabolism
What is creatine?
A muscle metabolite with constant production
How does serum creatine vary?
With muscle mass
What is the filtration process of creatine?
- Freely filtered by the glomerulus
- There is some additional secretion by the tubules
What is the equation for filtration fraction?
FF = GFR/renal plasma flow
What is the filtration fraction?
The proportion of renal blood flow that gets filtered
What is renal clearance?
The volume of plasma from which a substance is completely removed by the kidney per unit time (usually min)
What is the equation for renal clearance?
Clearance = (urine conc. x urine volume)/ plasma conc.
What are maintained constantly over a systemic mean arterial pressure over a range of 90-200mmHg (kidneys)?
Renal blood flow, capillary pressure and GFR
Is the constriction/dilation of the arterioles to control GFR dependent on nerve supply and/or blood borne substances?
Neither
What is the constriction and dilation of the arterioles to control GFR dependent on and why is it important?
- An intrinsic property of vascular smooth muscle
- To prevent an increase ion systemic arterial pressure from reaching and damaging capillaries
What is the mechanism to control GFR via arterioles?
- Pressure within afferent arterioles rises
- Stretching the smooth muscle wall
- Triggering the contraction of smooth muscle = arteriolar constriction
What is the GFR of an individual nephron regulated by?
The rate at which filtered fluid reaches the distal tubule
What do the cells of the macula densa (distal tubule) do in tubuloglomerular feedback?
Detect NaCl arrival
What do macula densa cells do in response to a reduction in NaCl?
Release prostaglandins
What do the release of prostaglandins in response to reduced NaCl from the macula densa cells do?
- Acts on granular cells
- Triggers renin release
- Activates RAAS system
What amount of filtrate passes through the tubules of the kidney a day?
180 litres
What is retained effectively in the kidneys?
Glucose and amino acids
What is the proximal convoluted tubule responsible for?
Bulk absorption (leaky)
What is the distal convoluted tubule responsible for?
Fine tuning (impermeable
What is the proximal tubule of the kidney responsible for bulk absorption of?
Na, Cl, Glucose, amino acids, bicarbonate
What is the proximal tubule of the kidney responsible for secretion of?
Organic ions
What are the main functions of the loop of Henle?
- More Na reabsorption
- Urinary dilution
- Generation of medullary hypertonicity
What is the generation of medullary hypertonicity?
Where the medulla of the kidney is very concentrated, meaning water wants to flow into it
What are the functions of the distal tubule?
- Fine regulation of Na, K, Ca, phosphate
- The separation of Na from water
Where does the separation of the salt from water occur?
The distal tubule of the kidney
What are the functions of the collecting duct of the kidney?
- Fine regulation of Na, K, Ca, phosphate
- Acid secretion
- Regulated water reabsorption (concentrating urine)
What is the bulk reabsorption of the proximal tubule driven by?
The basolateral Na/K ATPase
What happens to Cl in the second half of the proximal tubule?
It follows Na in the second half of the tubule
What is the water permeability of the proximal tubule?
High
Why is the proximal tubule vulnerable to ischaemic injury?
Due to its distance from the glomerulus
Which cells suffer if there is damage to perfusion to the kidney?
The cells of the proximal tubule - as they work very hard
What is the mechanism of primary active Na reabsorption in the proximal tubule?
- Na is actively transported out of the proximal cells and into the interstitial fluid by a Na/K ATPase pump (3 Na for 2 K)
- This then moves into the capillary
- There is active co-transport of Na into the proximal tubule cells (with glucose and phosphate)
- There is also co-transport with H ions, where Na moves into the proximal tubule cells and H moves out
- Water follows passively by osmosis
What drives the reabsorption of the glucose and phosphate and the secretion of hydrogen ions in the proximal tubule?
Na reabsorption
What is the process of proximal bicarbonate secretion?
- H ions which have been anti ported with Na combines with bicarbonate in the lumen
- This forms carbonic acid
- The CO2 and H2O formed by the splitting of carbonic anhydrase diffuse into the tubular cells
- These reform carbonic acid
- Splits into bicarbonate and H+
- Bicarbonate is actively symported into the lumen of the capillary with Na ions
What causes the proximal convoluted tubule to be leaky?
Weak tight junctions at the border of membrane cells
What is the transport maximum of the kidney?
Limits to the amounts of material they can transport per unit time due to binding of membrane transport proteins
What does efferent arteriolar constriction do to peritubular capillary hydrostatic pressure?
Reduces it
Is the descending limb of the loop of Henle permeable or impermeable?
Permeable
Is the ascending limb of the loop of Henle permeable or impermeable?
Impermeable
Where does solute reabsorption happen in the loop of Henle?
In the thick ascending limb
Where does urine concentration happen in the loop of Henle?
As tubular fluid flows through the medullary collecting ducts
What happens to the interstitial fluid surrounding the medullary collecting ducts in the presence of vasopressin (ADH)?
- Water diffuses out of the ducts into the interstitial fluid of the medulla
- Enters the blood vessels of the medulla to be carried away
What happens along the length of the ascending limb of the loop of Henle in relation to countercurrent flow?
- Na & Cl are reabsorbed from the medullary interstitial fluid
- In the upper thick portions, this happens through cotransport through transporters
- In the lower ascending limb, it occurs by simple diffusion
What happens along the length of the descending limb of the loop of Henle in relation to countercurrent flow?
- It is permeable to water, but doesn’t reabsorb Na or Cl
- Net diffusion of water out of the descending limb into interstitial fluid until osmolarities are equal again
What are the specialised blood vessels of the medulla of the kidney?
The vasa recta
Where do the vasa recta run?
- Form hairpin loops
- Run parallel to the loops of Henle and medullary collecting ducts
What happens to transport of contents of the vasa recta as it goes deeper into the medulla?
- Na/Cl diffuse into the vasa recta
- Water diffuses out the vessel
What happens to transport of contents of the vasa recta as it goes superficial from the medulla?
- Na/Cl diffuse out of the vasa recta
- Water diffuses into the vessel
What happens as urea passes through the remainder of the nephron?
It is reabsorbed, secreted into the tubule and then reabsorbed again
What happens to the urea that has accumulated in the medullary interstitum?
In the thin descending and ascending limbs of the loop of Henle, the accumulated urea is secreted back into the tubular lumen by facilitated diffusion
Where is there continued active dilution of urine by reabsorption of Na in water (impermeable)?
The distal tubule
Is the collecting duct permeable to water?
Highly water impermeable
What are the two cells types of the collecting duct?
Principle cells and intercalated cells
What is the action of aldosterone on the principle cells of the collecting duct?
- Increases Na influx
- This charge movement facilitates K efflux
- Drives both Na reabsorption and K secretion
What is the action of vasopressin (ADH) on the principle cells of the collecting duct?
- ADH binds to a receptor on the surface
- This results in the insertion of vesicles into the apical membrane
- Increases water
permeability and
reabsorption of water giving a more concentrated urine
What is the function of the intercalated cell?
Secretes acid into the collecting duct
What is the major cation in the extracellular space of the body?
Sodium
What is the major cation in the intracellular space of the body?
Potassium
What is the intracellular pH?
7
What is the extracellular pH?
7.4
What is fluid movement regulated by?
Controlling Na movement
What is tonicity regulated by?
Controlling water movement
Where is vasopressin synthesised?
Hypothalamus
Where is vasopressin secreted from?
Posterior pituitary
What controls the release of vasopressin?
Hypothalamic osmoreceptors
What does vasopressin do in terms of blood pressure?
It is a widespread arteriolar constrictor
How do baroreceptors help control vasopressin secretion?
- Reduced plasma volume
- Reduced venous/atrial/arterial pressures
- Reflexes mediated by cardiovascular baroreceptors
- Increased vasopressin secretion from posterior pituitary
- Increased tubular permeability to water
- More water reabsorption
- Less water excretion
What can stimulate vasopressin secretion?
Thirst - leads to increased water reabsorption
When does urinary Na excretion increase?
When there is an excess in the body
The responses which regulate urinary Na excretion are instate mainly by what?
- Cardiovasulcar baroreceptors (e.g. carotid sinus)
- Sensors in the kidneys e.g. the cells in the macula densa of the DCT
How is low total-body sodium related to cardiovascular pressure?
Low total-body sodium = low plasma volume = decrease in cardiovascular pressure
How can the control of GFR alter Na reabsorption?
- Low Na elicits a decrease in GFR, which in turn gives reduced net glomerular filtration pressure
- Decrease in cardiovascular pressure naturally gives vasoconstriction, mainly of the afferent arteriole
- This reduces GFR
What is the major factor determining the rate of tubular Na reabsorption?
Aldosterone
What are the 3 controlling steps in the initiation of RAAS?
- When the cells of the macula densa in the distal convoluted tubule detect LESS NaCl in the tubule
- Sympathetic stimulation
- Little or no arteriolar stretch (low blood volume)
What happens after RAAS has been initiated?
Juxtaglomerular cells in the afferent arterioles are stimulated to release renin
What is the RAAS system?
- Angiotensinogen (produced in liver) is cleaved by renin (from kidneys) to produce angiotensin I
- Angiotensin I is converted into angiotensin II by ACE (produced in lungs)
What are the functions of angiotensin II?
- Stimulates the secretion of aldosterone from the adrenal glands
- Aldosterone causes vasoconstriction, hence resulting in increased GFR
- Increases Na reabsorption in PCT
- Stimulate thirst
- Stimulate vasopressin release
What is aldosterone?
A steroid hormone that is secreted and produced by the zona glomerulosa cells in the adrenal cortex of the supradrenal/adrenal glands
What is the function of aldosterone?
- Acts on the principle cells of the collecting duct
- Increases Na & water reabsorption
- As it works by exchanging Na for K - reabsorb more Na = leak more K
What is ANP?
- Atrial natriuretic peptide
- Controls Na reabsorption
Where is ANP synthesised and secreted from?
The cardiac atria
How does ANP work in relation to Na?
Acts on tubular segments to inhibit Na reabsorption
How does ANP work in relation to vasodilation/GFR?
- It acts as a renal vasodilator
- Gives afferent arteriole dilation
- Increases GFR - further Na excretion
How does ANP work in relation to aldosterone?
ANP inhibits aldosterone, so increases Na excretion
When does the secretion of ANP increase in the body?
- When there is an excess of Na in the body
- Excess Na = more H2O in vessels
- Increase blood volume = stretched atria
- Stimulates ANP