Organisation of renal system - 1 Flashcards
The arrangement of nephrons within kidney give rise to 2 distinct regions at macroscopic layer:
Outer region: Renal cortex - capillary, convoluted tubules, peripheral blood supply to nephron
Inner region: Renal medulla - collecting duct and loop of Henle
Vascular components
Where does kidney gets blood supply
Explain the pathway
Kidney gets blood supply from renal artery which
afferent arterioles: branched capillary structure known as glomerulus
Highly branched capillary structure surrounded nephron: peritubular capillaries
Afferent towards Efferent away
Aorta → Renal Artery → Afferent Arteriole → Glomerulus → Efferent Arteriole → Peritubular capillaries → Renal Vein → Inferior Vena Cava
What happens in the glomerulus?
Water and solutes are filtered through the glomerulus as blood passes through it
It is a key nephron structure
Tubular component of nephron structure?
Hollow, fluid-filled tube formed by a single layer of epithelial cells
Bowman’s capsule - where does initial filtrate have to do with this?
Initial filtrate comes into tubule
Components of tubular component: see slide 12
1.Bowman’s capsule
2. Proximal tubule
3. Loop of Henle
– Descending limb
– Ascending limb
4. Juxtaglomerular apparatus: specialised area
5. Distal tubule
6. Collecting duct or tubule: urine ultimately flows to urethra after this
2 types of nephrons:
- Cortical - secretion and reabsorption of materials
- Juxtamedullary - accompained by vasoerect specialised vasculature which is important for making congration gradients which is important for secretion of urine etc
85% are corical nephrons which are shorter
They are the most abundant type of nephron
The basement membrane is made up of?
Globuluar proteins
3 basic renal processes:
Glomerular filtration
Tubular reabsorption
Tubular secretion
Glomerular filtration all have what charge?
Negative
What also influences solutes moving in and out?
Electrical charge and Osmotic gradient
Fluid filtered from the glomerulus into Bowman’s capsule pass through 3 layers of the glomerular membrane (all –ve charge) - these are?
- Endothelial cells of the Glomerular capillary wall
- Basement membrane
- Inner layer of bowman’s capsule of glomerular filtration
Glomerular filtration via membrane - Basement membrane what kind of layer and composed of?
Not made of cells
Has an acellular gelatinous layer
Composed of (-) charged glycoproteins, collage IV, laminin
Inner layer of bowman’s capsule of glomerular filtration:
1. Line up where and what does this limit?
2. Consists of?
3. Podocytes have what?
4. What arises between podocytes?
- Line up end feet along basement membrane along projections and help limit what can pass across and prevent large molecules from moving across
- Consists of epithelial cells of bowman’s capsule, i.e. podocytes that encircle the glomerulus tuft
- These podocytes have long projections from which foot processes arise
- Filtration slits arise between them
Forces involved in glomerular filtration:
Glomerular capillary blood pressure (+)
Plasma-colloid osmotic pressure (-)
Bowman’s capsule hydrostatic pressure (-)
Results in => Net filtration pressure (+) which is why we get about 20% filtration of plasma
What is the main factor for the force of capillary blood pressure on glomerular filtration?
Afferent and efferent arteriolar effect on it?
Main factor: Larger diameter afferent vs efferent arteriole
(influenced by the state of vasoconstriction of both arterioles).
Afferent arteriolar constriction reduces GF.
Efferent arteriolar constriction increases GF.
Explain how the 3 physical forces of:
1. Glomerular capillary blood pressure (+)
2. Plasma-colloid osmotic pressure (-), Bowman’s capsule hydrostatic pressure (-)
3. Net filtration pressure (+) are involved in glomerular filtration:
- Glomerular capillary blood pressure (+)
Main factor: Larger diameter afferent vs efferent arteriole
(influenced by the state of vasoconstriction of both arterioles).
Afferent arteriolar constriction reduces GF.
Efferent arteriolar constriction increases GF. - Plasma-colloid osmotic pressure (-)
conc. osmotically active components
Large plasma proteins are not filtered in the glomerulus
plasma/filtered fluid (albumin)
– Bowman’s capsule hydrostatic pressure (-) - Net filtration pressure (+)+
pressure exerted by fluid in the initial part of Bowman’s capsule
What is GFR?
What is it important to differentiate between in terms of filtrartion and urine?
Volume of filtrate made by both kidneys per minute
Important to distinguish between filtration fraction and rate and what is actually released in urine
Glomerular filtration rate: GFR?
Approx 125 ml/min in a normal adult/180L/day => gold standard of kidney function
Chronic kidney disease: what is it
Irreversible, substantial, and longstanding loss of renal function for >3 months based on abnormal structure or function, or GFR <60mL/min for >3 months with or without evidence of kidney damage.
Chronic kidney disease:
Stage 1,2,3A,3B,4,5 and their GFR in mL/min:
1 >90
2 60–89
3A 45-59
3B 30–44
4 15–29
5 15–29
Causes of chronic kidney disease: 5
1 Diabetes: 20% UK, 43% USA. Type II»_space; type I
2 Glomerulonephritis: commonly IgA nephropathy, also rarer disorders, eg mesangiocapillary GN, systemic disorders, eg SLE, vasculitis
3 Unknown: up to 20% in the UK have no obvious cause of CKD, many of these present late with small, shrunken kidneys where a biopsy would be uninformative
4 Hypertension or renovascular disease
5 Pyelonephritis and reflux nephropathy
- What is glomerulonephritis?
- How is it identified?
- What does it present by? 5
- Characterised by?
- Inflammatory process primarily involving the glomerulus - Nephrons making them lose function
- Identification of the histopathologic pattern of glomerular injury by renal biopsy
- Presents with: hypertension, oedema, urine sample, showing red blood cells, red blood cell casts: should never be in urine, proteinuria: proteins that shouldn’t be in urine are
- Characterised by: heavy proteinuria (> 3.5 g/24 h) and hypoalbuminemia (< 3.5 g/dL) in plasma - if albumin is passing into urine when it shouldn’t be then plasma will show this
Consequences of glomerulonephritis:
- Damage to glomerulus restricts blood flow, leading to compensatory increase bp
- Damage to filtration mechanism allows protein and blood to enter the urine
- Loss of usual filtration capacity leads to acute kidney injury
Depending on degree of inflammation of glomerulonephritis, patients therefore present with a spectrum of disease in terms of b.p, urine dipstick and renal function:
- Blood pressure - normal to severe hypertension
- Urine dipstick - proteinuria mild to nephrotic and haematuria mild to macroscopic
- Renal function - normal to severe impairment
Urinary Tract obstruction what happens?
Frequent effect involves?
Are obstructions painful - explain?
Reduce urinary flow and impair renal function
A frequent effect of a partial or complete obstruction is a dilation of the renal pelvic (hydronephrosis)
Obstructions of the urinary tract are painful and need immediate treatment due to the failure of renal function (reduced GFR)
Assessment of GFR using inulin
What is GFR?
Inulin is made by?
Research is?
Clinical note is?
Plasma renal clearance of a substance filtered but not reabsorbed or secreted = GFR
Inulin is made by vegetables such as onions and it has useful property where if its in urine its in glomerular filtration it does not undergo tubular component so if it is being excreted there is a problem
Research: inulin
Clinical note: creatine
What is PAH?
PAH clearance?
Any pAH that is not filtered is?
Para-aminohippuric acid – organic anion
Renal plasma flow
Secreted from peritubular capillary
Glomerular filtration rate depends on? 3
- Net filtration pressure
- Glomerular surface area
- Permeability of the glomerular membrane
If GFR is too low?
If GFR is too high?
If too low – everything is reabsorbed – including wastes
If too high – substances that are needed cannot be
reabsorbed quickly enough and are lost in the urine
3 major mechanisms control GFR:
- Intrinsic (autoregulation)
a. Myogenic mechanism
b. Tubuloglomerular feedback - Neural
- Hormonal
RBF: Renal blood flow is how much of CO?
RBF determines?
It is regulated how and between?
approx 25% - 1.1l/min
GFR
Auto regulated between 80+180 mmHg
Explain RBF Auto-regulation:
What is the mechanism and feedback?
Uncouples renal function from arterial blood pressure and ensures that fluid and solute excretion is constant
2 things:
1. Myogenic mechanism
2. Tubuloglomerular feedback
Explain myogenic mechanism of RBF autoregulation:
Based around constriction and dilation of afferent
localised control
When arterial pressure increases, the renal afferent arteriole have characteristics where they contract to respond to the pressure and they can stretch and then flow is increased. The vascular smooth muscle contracts to increase resistance and thus reduce flow to normal
Myogenic mechanism:
1. Arteriolar vasoconstriction effect on GFR?
2. Arteriolar vasodilation effect on GFR?
- Decreases
- Increases
LEARNING OUTCOMES
Structural overview of the kidney – vascular and tubular arrangement of the nephron
Factors affecting and assessment of glomerular filtration
Autoregulation of GFR
- Components of renal system
- Structure of nephron
- Basic renal functions
- Filtration and control
- Assessment of filtration
Structures that carry urine from the kidneys to the outside for elimination?
Ureters, urinary bladder and urethra
Structures that support/modulate renal function:
Arterial Vascular system and Adrenal gland
Kidneys perform a variety of functions aimed at?
Maintaining homeostasis
Kidneys are urine forming organs
Their weight?
Also known as?
Retroperitoneal
Typical weight ~130g each
Functions of kidney: 10
- Maintain H2O and salt balance in the body
- Maintain proper osmolarity of body fluids, primarily
through regulating H2O balance - Regulate the quantity and concentration of most ECF ions
- Maintain proper plasma volume
- Help maintain proper acid-base balance in the body
- Excreting (eliminating) the end products (wastes) of
bodily metabolism and drug metabolites - Excreting many foreign compounds
- Producing erythropoietin (erythrocytes formation)
- Producing renin (Blood pressure control)
- Converting vitamin D into its active form
Ureters are ducts - with what kind of wall?
Smooth muscle walled duct
Ureters carry urine where?
To the urinary bladder
Where do the ureters exit from?
Exits each kidney at the medial border in close proximity to renal artery and vein
What does the urinary bladder temporaily store?
Urine
Urinary bladder - How does it empty fluid?
Periodically empties to the outside of the body through the urethra
Structure of the urinary bladder?
Hollow, distensible, smooth muscle lining wall
What does the urethra do?
Conveys urine to the outside of the body
Urethra in females vs males structure?
In females it is straight and short
In makes it is much longer and follows curving course from bladder to outside
Dual function of urethra in males?
Provides route for eliminating urine from bladder and is a passageway for semen from reproductive organs
Sphincter of urethra internally and externally - what kind of muscle?
Internal: smooth muscle
External: skeletal striated muscle
What is the nephron? and how many is there?
Nephron is the functional unit of the kidney with ~1 million nephrons/kidney
What is in the vascular and tubular components of the nephron?
Vascular component:
➢Glomerulus
➢Afferent arteriole
➢Efferent arteriole
➢Peritubular capillaries
Tubular component:
➢Bowman’s capsure
➢Loop of Henle
➢Proximal convoluted tubule
➢Distal convoluted tubule
Fluid is filtered from the glomerulus into Bowman’s capsule and it passes through 3 layers of the glomerular membrane which are?
Fenestrated endothelial cells
Glomerular basement membrane
Podocytes
Glomerulus accounts for approx how much of cardiac ouput?
20-25%
The Juxtamedullary nephron is a long-looped nephron important in establishing what?
Establishing the medullary vertical osmotic gradient
SEE SLIDE 15+16 DIAGRAMS
Mesangial cells
1. They are exposed to macromolecules how?
2. Separated by?
3. They stop what?
4. Function in?
5. Their movement involves?
- Exposed to macromolecules from the capillary lumen
- Separated only by fenestrated endothelium without basement membrane
- They stop macromolecules from accumulating in the mesangial space by phagocytosis and pinocytosis
- They regulate capillary flow
- By contracting and relaxing
Anything that is filtered/secreted but not reabsorbed is removed how from the body?
Excreted via urine
Glomerular filtration what is it?
Nondiscriminant filtration of a protein- free plasma from the glomerulus into Bowman’s capsule
Tubular reabsorption what is it?
Selective movement of filtered substances from the tubular lumen into the peritubular capillaries
Tubular secretion what is it?
Selective movement of non filtered substances from the peritubular capillaries into the tubular lumen
How much of the plasma that enters the glomerulus is filtered and how much is not and leaves via the efferent arteriole?
20% of plasma that enters the glomerulus is filtered and 80% is not and leaves via efferent arteriole
Urea is the metabolism of?
Nitrogen containing compounds
Major filtered substances - which are reabsorbed and which are excreted?
Water is 99% reabsorbed and 1% excreted
Sodium is 99.% reabsorbed and 0.5% excreted
Glucose is 100% reabsorbed and 0% excreted
Urea (waste product) is 50% reabsorbed and 50% excreted
Phenol (waste product) is 0% reabsorbed and 100% excreted
Glomerular filtration via membrane - The endothelial cells of the glomerular capillary wall:
1. Are permeable to?
2. Made up of?
3. Highly filled with what?
- Permeable to water and solutes
- Thin single layer of epithelial cells
- Highly fenestrated i.e. with numerous pores filled with negatively charged glycoprotein - i.e. podocalyxin
Glomerular filtrate the ultrafiltrate consists of?
Is cell and protein FREE
Glomerular filtrate size and charge?
Serum albumin has a radius if about 3.5 nm (69kDa) but its negative charge prevents its movement across basement membrane
What is Proteinuria?
In some diseases the negative charge on the filtration barrier is lost so that proteins are more readily filtered = Proteinuria
Glomerular epithelial cell injury and destruction of the basement membrane what is found present in membrane?
Albumin (69 kDa), is present in urine if the membrane is damaged (normally repelled by -ve charged basement membrane)
- What is Nephr-I-tic syndrome?
- What is Nephr-O-tic sydnrome?
See slide 28 for table on it
- Pores in glomerular membrane become large
enough for proteins and red blood cells to pass into the urine. Hematuria, hypertension, oliguria (urine output < 400mL/day), mild-to-moderate proteinuria - Excessive proteinuria, hypoalbuminemia, oedema, hyperlipidemia (oliguria uncommon)
Pathologically with GFR what can change with-
1. Plasma-colloid osmotic pressure?
2. Bowman’s capsule Hydrostatic pressure?
Explain
- Plasma-colloid osmotic pressure
- Dehydrating diarrhea
- Relative increase in colloid pressure in glomerulus
- increase in pressure opposing filtration
↓ GFR - Bowman’s capsule hydrostatic pressure
-kidney stone/obstruction of tubule with enlarged
prostate
- increase in capsular hydrostatic pressure
-↓ GFR
Explain Tubuloglomerular feedback in RBF - autoregulation?
What substances are involved?
See diagrams 37+38+39
The juxtaglomerular apparatus (JGA) is located between the afferent arteriole and the returning distal convoluted tubule of the same nephron.
Alteration of tubular flow is sensed by the macula densa of the juxtaglomerular apparatus (JGA) and produces a signal that alters GFR
Endothelin/Adenosine/ATP/Bradykinin
GFR can also be influenced by changes in the filtration coefficient (Kf) by Mesangial Cell Contraction -
1. The contract in response to?
2. Mesangial cells are what?
3. What is Kf?
- They contract in response to an increase in angiotensin resulting in a decrease in surface area available for filtration.
- Mesangial cells are modified smooth muscle cells located on glomerular capillaries.
- Filtration coefficient is a measure of a membrane’s permeability to water
