Renal Flashcards
What might renal disease be a result of?
- Age
- Viral, fungal or bacterial infections
- Parasites
- Cancer
- Amyloidosis – abnormal deposits of a type of protein in the kidney
- Inflammation
- Autoimmune disease
- Trauma
- Toxic reaction to poisons or medications
- Congenital and inherited disorders
What are the 6 renal functions?
- Regulation of water balance between intake and output
- Regulation of salt balance – performed by the kidney alone in most animals
- Conservation and regulation of essential substances, such as glucose, amino acids and calcium ions
- Removal of metabolic waste products, such as urea, uric acid, creatinine and ammonia
- Removal of foreign substances such as drugs or metabolites
- Regulation of pH via ions such as H+ and HCO3-
What are the 3 renal endocrine functions?
- Active form of vitamin D – important for calcium and phosphate absorption from the gut
- Renin – renin-angiotensin-aldosterone system for control of blood pressure
- Erythropoietin – synthesis of red blood cells
What is water balance and what affects it?
Water in = water out
- Dry food or wet food will effect water intake
- Physiological factors, such as lactation
- Dry vs humid environment will effect water output
Describe isotonic conditions.
- No net movement of water
- No change in cell volume
- Effective osmotic pressure is the same in ECF and ICF
- Normal saline (0.9% NaCl)
Describe hypotonic conditions.
- Net inward movement of water
- Cell volume increases and may lead to lysis
- Effective osmotic pressure/tonicity is lower in ECF then ICF
- Pure water
Describe hypertonic conditions.
- Net outward movement of water
- Cell volume decreases in crenation
- Effective osmotic pressure/tonicity is greater in ECF than ICF
- Sea water or fluid in renal medulla
How do kidneys differ between vertebrates?
Common to all vertebrates and all can produce hypotonic or isotonic urine.
Birds and mammals have hypertonic urine and have the distinguishing feature of the Loop of Henle.
Describe the position of the kidneys.
- Retroperitoneal
- Connected to bladder via ureters
- Bladder connected to outside world via urethra
- Each has an adrenal gland sitting over the top of it
How are the kidneys supplied?
The kidneys receive 20% of cardiac output.
- Supplied by renal arteries, branches of the aorta
- Venous drainage through the renal veins, which feeds into the caudal vena cava
- Blood vessels, sympathetic nerve supply and ureter enter and exit the kidney via the renal hilus
Describe the general structure of the kidneys.
- Each kidney is surrounded by renal capsule
- Renal cortex around the outside
- Renal medulla on the inside
- Renal pelvis in the centre
- Medulla divided into renal pyramids
- Renal artery branches up in medulla and cortex
- Nephrons in renal pyramids
- Collecting duct from renal medulla to renal pelvis through the renal papilla
- Region outside each papilla is a calyx, a part of the renal pelvis
Distinguish juxtamedullary nephrons and cortical/subcapsular nephrons.
Juxtamedullary nephrons – long proximal tubule, long Loop of Henle, 20% of nephrons
Cortical/sub-capsular nephrons – short proximal tubule, short Loop of Henle, 80% of nephrons
Describe the structure of the nephron.
- Glomerulus – arterial blood forms a capillary network within a Bowman’s capsule. Site of ultrafiltration.
- Proximal tubule – most of the filtrate is reabsorbed along with vital nutrients.
- Loop of Henle and collecting duct – control urine concentration in medullary nephrons.
- Distal tubule – fine tuning of electrolyte concentrations.
- Juxta-glomerular apparatus – production of renin hormone
What is the blood supply to the nephron?
Afferent arteriole > Bowman’s capsule > efferent arteriole > peritubular capillaries – which descend and ascend into the medulla to allow full flow between the limbs of the Loop of Henle.
What 3 layers is fluid filtered across in the glomerulus and Bowman’s capsule?
Endothelial cell of capillary
- Flattened cells with thin cytoplasm
- Fenestration of diameter 60nm are lined with negatively charged glycoproteins and increase permeability
- Prevent red blood cells and platelets leaving capillaries
Glomerular basement membrane
- Non-cellular, continuous layer of collagen and glycoproteins
- Main function is to act as a barrier to filtration of large molecules
Visceral epithelial cell/podocyte of bowman’s capsule
- Made up of cell body, trabeculae and pedicels
- Main functions: maintenance of basement membrane, and slit pores between pedicels are lined with negatively charged molecules for perm selectivity
What is the composition of ultrafiltrate?
- Small molecules and ions in almost exactly same concentration as plasma
- No proteins such as albumen
- No blood cells
- Greater restrictions on filtration for negatively charged molecules
Why is glomerular filtration rate clinically important and what are the forces determining it?
GFR is clinically important, as it is vital for normal kidney function. GFR can be impaired in many conditions: infections, parasites, congenital conditions.
The forces that determine GFR are Starling’s Forces – the oncotic and hydrostatic pressures.
How is net filtration pressure calculated?
Net filtration pressure, NEP = forces out – forces in
= (Pcapillary +oncotic bc) – (Pbc + Pbowman’scapsule)
0 = oncotic bc under normal conditions
= Pcap – (oncotic cap +Pbc)
What is the effect of constriction in the afferent and efferent arterioles?
Constriction of afferent arteriole > decreased hydrostatic pressure and blood flow in glomerular capillary > reduced filtration
Constriction in efferent arteriole > increased hydrostatic pressure and decreased blood flow in glomerular capillary > little change in filtration
Name some other factors that affect glomerular filtration rate.
- Low blood pressure – renal failure, no filtration
- Long term high blood pressure – damage to the filtration barrier
- Kidney stones – blockage in the ureter, decreased filtration
- Low protein – decreased oncotic pressure, increased filtration
- Nephrotic syndrome – failure of filtration barrier. Increased oncotic pressure and increased filtration
Define clearance.
A measure at the efficiency or effectiveness of the kidney in removing a substance from the blood. For example, how quickly does the kidney remove a drug from the circulation, so that the right dosage and regime can be used.
Describe the process of clearance.
- Concentration of [molecule] is [6] per unit volume of blood.
- These enter the kidney at the glomerulus via the afferent arteriole.
- They flow round and into the glomerular capillaries and along with filtration, a proportion of these molecules are filtered into the Bowman’s space and inner proximal tubule along with the filtrate.
- Remaining [molecules] will flow out through the efferent arteriole and into the peritubular capillaries.
- Because some [molecules] have been lost in filtration, the concentration in the peritubular capillaries is only 3 [molecules] per the original volume of blood.
- Some [molecules] that have been filtered out of the blood may be reabsorbed back into the peritubular capillaries. So the amount of [molecules] left in the filtrate may be 2.
- There is a lower concentration of [molecules] in the blood leaving the kidney.
- So the clearance is an indication of how much blood would have been cleared of that substance on 1 passage through the kidney in ml/min.
How is clearance calculated?
= (concentration in urine x volume of urine produced) / concentration in plasma
(ml/min)
How is creatinine used as a measure for glomerular filtration rate?
Creatinine is a breakdown product from muscles.
- It is present in steady concentrations in the blood.
- Can be used to measure GFR because it is freely filtered into the filtrate.
- Some is filtered and some remains in the blood but there is no reabsorption or secretion of creatinine.
- So the clearance of creatinine is equal to the GFR because none of it is secreted or reabsorbed and it is freely filtered.
- Amount per minute in urine = amount filtered per minute.
How is inulin used as a measure for glomerular filtration rate?
Inulin is the gold standard to measure GFR but you would need to give an inulin infusion, as it is not a naturally occurring substance. Creatine is acceptable but not gold standard.
How are clearance ratios used to show how substances are handled within the kidney?
- If the clearance of substance X is lower = X is not freely filtered OR X is reabsorbed. A common example being glucose.
- If the clearance of X is higher = X is secreted from the tubule into the peritubular blood supply. This is the only explanation, as the plasma can only be filtered at the same rate as filtration is occurring. A common example being penicillin.
What is para-amminohippuric acid?
An organic acid that is freely filtered into the filtrate and the remainder is secreted into the proximal tubule.
It has a transport maximum limit, but below that limit, it is all secreted into the tubule.
PAH that appears in the urine = the amount that is + the amount that is secreted.
As all the plasma is cleared of PAH secretion into the tubule, we can see that the clearance of a substance = the amount of plasma that flows through the kidney.
What is filtration fraction and how is it calculated?
The filtration fraction – the proportion of the plasma flow through the glomerulus that is filtered. This can be calculated using:
• GFR – from clearance of inulin or creatinine
• Renal plasma flow – clearance of PAH
FF = GFR / RPF
Normally between 0.15-0.2
What is the effect of autoregulation of renal blood flow?
Acts to maintain the consistency of blood flow and GFR.
- Renal blood flow is approximately 20% of cardiac output.
- Renal blood flow and GFR are very constant and independent of arterial blood pressure, which is around 80-180mmHg.
- In renal blood flow between 80-180mmHg, there is a plateau, showing that is very constant in between these values.
- When the renal blood flow is kept relatively constant between 80-180mmHg, GFR remains at a relatively constant level.
- Unlike this, the change in urinary volume does increase more linearly as blood pressure increases.
How is renal blood flow intrinsically controlled?
- Myogenic activity – increased arteriole pressure lead to stretch in the arteriole wall, causing smooth muscle to contract and therefore reduce flow.
- Tubulo-glomerular feedback – due to tasting of fluid in the distal tubule within the macula densa within the duct to the glomerular apparatus. This is tasting by the sodium or chloride levels. This leads to a constriction of afferent arterioles, likely via a vasoconstrictor from the juxtaglomerular apparatus.
How is renal blood flow extrinsically controlled?
- Sympathetic vasoconstrictor activity – minimal at rest but increases with changes, such as exercise, pain or cold
- Vasoconstrictors in kidneys is attenuated by local release of vasodilators, such as prostaglandins and nitrogen oxides.
- Severe reduction in arterial blood pressure will depress RBF and may lead to acute renal failure.
What is reabsorbed in the proximal tubule?
- Sodium
- Chloride
- Glucose
- Amino acids
- Peptides
- Metabolites
- Urea
- Water
Name the 2 mechanisms that substances can be secreted into the tubule.
- Organic acids
* Organic bases
Describe the structure of the proximal convoluted tubule.
- Tubular lumen
- The cells that make up the tubular/nephron wall – single layer of cuboidal epithelial cells
- Peritubular capillary cells
- Interstitial fluid between the tubular cells and the capillary
- Side of tubular cells closest to the tubular lumen is the apical surface
- Side of the tubular cells closest to the interstitial fluid is the basal surface
- Basolateral spaces on basal side of tubular cells caused by invaginations of the basal lateral membrane
Describe reabsorption across the proximal convoluted tubule.
- Reabsorption of substances occurs by the movement of solutes form the tubular lumen to the capillaries
- Secretions of substances refers to the movement of solutes from the capillaries to the tubular movement, and eventually into the urine
There are different routes that substances can take:
- Paracellular route that substances can be reabsorbed by, which goes in between the tubular cells
- Transcellular route where substances move from the tubular cell lumen and through the cells to the capillary lumens
Which transport mechanisms are used for reabsorption?
- Active – metabolic energy is required
- Passive – no metabolic energy required
- Primary active transport – coupled to ATP hydrolysis. In the kidney, the most important are sodium-potassium-ATPase, but you can also find calcium-ATPase, hydrogen-ATPase and hydrogen-potassium-ATPase.
- Secondary active transport – relies on the sodium gradient set up by sodium-potassium-ATPases, leaving low sodium concentration inside cells, which drives the transport of sodium coupled with other solutes
What are the adaptations of the proximal tubule for reabsorption?
- Located immediately after the glomerulus – so reabsorption can occur as soon as possible following filtration
- Convoluted – twists so a longer length of tubule can fit in the same volume of kidney tissue
- Peritubular blood from efferent arteriole has a high oncotic pressure due to the bulk filtration of water and oncotic solutes. This will favour the movement of water from the tubule to the peritubular capillaries
- Cells of proximal tubule are tightly adhered to each other at the basal side by tight junctions, preventing too much movement of solutes between cells rather than transcellular movement.
What are the adaptations of tubular cells in the proximal convoluted tubule for reabsorption?
- Brush border on the apical surface that increases the surface area of the nephron lumen
- Infolding in the basal membrane is a site where high osmolarity can build up
- Many mitochondria for high levels of ATPase activity in the transport of different substances
- Carriers and transporters for different solutes
What is the presence of sodium-potassium-ATPase
The presence of sodium-potassium-ATPase in the basal/basolateral membranes is the main driving force for the reabsorption. This sets up a low intracellular sodium content and a negative intracellular potential of -70mV. There are many proteins carriers on the apical surface that take advantage of these things.
What are the 2 types of movement across the apical membrane?
Symport – co-transport in the same direction as sodium transport
Antiport – sodium travelling down concentration gradient will drive exchange of counter transport with another ion
How is glucose reabsorbed?
- Reabsorption occurs against its concentration gradient in co-transport with sodium out of tubular lumen > into the cell > transporters on the basal membrane > bloodstream.
- Relies on sodium being moved into the cells down its concentration gradient
- Glucose is freely filtered
- Normally almost all filtered glucose is reabsorbed in the proximal tubule
- However, there is a transport maximum (Tmax) that is reached when all sodium-glucose transporters are fully occupied and no more reabsorption can occur.
- This is when glucose is excreted in the urine, glucosurea.
- Glucosurea can occur transiently in pregnancy or in diabetes mellitis.
- When glucose is excreted it can lead to excessive water loss, leading to dehydration and excessive thirst. This is because osmolarity of the tubular fluid is increased and will automatically take water with it.
How is chloride and bicarbonate reabsorbed?
- Chloride concentration in the tubule increases as sodium is reabsorbed
- Chloride reabsorption occurs via the transcellular or paracellular route, particularly paracellular in the later proximal tubule.
- Bicarbonate is reabsorbed from the proximal tubule, which is significant in pH control.
How is potassium reabsorbed?
Potassium is at a much lower concentration than many other ions in plasma and extracellular fluid. But potassium is reabsorbed in the proximal tubule, mostly passively via the paracellular route as the concentration increases due to the absorption of water.
How are peptides reabsorbed?
Peptides are removed from the tubule by endocytosis at the apical membrane and within the vesicles, they are broken down into amino acids. These amino acids are then reabsorbed back into the blood supply by co-transport with sodium on the basal membrane and then into the capillary.
