Pharmacology Part 2 Flashcards
List the multiple functions of the Kidney
The functions of the Kidney include:
- Excretion: getting rid of metabolic waste including urea, creatinine, uric acid, end products of breakdown
- Control of water and electrolytes (K+, Na+, Cl-)
- Control of arterial blood pressure
- Control of acid-base balance
- Endocrine functions like renin release
- Glucose synthesis during prolonged fasting
Understand the unique nature of kidney blood supply due to the presence of two capillary beds - glomerular and peritubular capillaries
Blood circulation in the Kidney is unique as it has two capillary beds
Firstly, the afferent arteriole delivers blood to the glomerular capillaries where filtration occurs. The glomerular capillaries then rejoin to form the efferent arterioles where the unfiltered components of the blood leaves the glomerulus
Efferent arterioles subdivide into peritubular capillaries which supply blood all around the rest of the kidney essentially
Describe the nephron as the functional unit of the kidney with 5 anatomical region
The 5 anatomical regions of the Kidney are:
- Renal corpuscle. This contains the Bowman’s capsule and the glomerulus. In this region, the blood is filtered under high pressure from the glomerular capillaries into the bowman’s space through a process called ultrafiltration
- Next is the Proximal convoluted Tubule. The fluid from the Bowman’s capsule enters here. The entirety of the PCT is in the cortex of the kidney. The cells contain a single layer of cuboidal cells connected by tight junctions as well as microvilli which increase their SA and for such reason it is the key site of reabsorption of nutrients back into the blood.
- Next is the Loop Of Henle which forms a U shaped hairpin that starts in the cortex of the kidney but dips into the medulla with its thin descending limb. From here, depending on whether the nephron contains a long loop of Henle or a short loop, the ascending will either be thin then thick, or it will go straight into the thick ascending limb
- Next is The Macula Desna which sits on top of the loop of henle and it is a short segment of specialized cells. They form apart of the juxtaflomerular apparatus which play an important role in controlling nephron function. They also secrete renin
- Finally the Distal convoluted is shorter and less convoluted than the proximal convoluted tubule. The fluid enters the Collecting duct from here. The collecting duct is formed from two types of cells Principal P, and Intercalated I cells which are both involved in acid base balance.
Each collecting duct may drain fluid from up to 8 nephrons
Describe the innervations of the kidney
There are NO parasympathetic nervous innervation, only sympathetic
Sympathetic activation of Alpha adrenoceptors on smooth muscle cause smooth muscle contraction of afferent and efferent arterioles
Sympathetic activation of Beta adrenoceptors on juxtaglomerular cells cause the activation of renin secretion
State the 3 renal process involved in urinary excretion and explain them
Ulrafilraiton - This is the movement od subsances from the glomerulus to the bowmans capsule under high hydrostatic pressure to produce an ultrafiltrate whoch is modified in the subsequent steps
Reabsorption - This is the movement of substances from the lumen back into the blood The vessels they move into are the peritubular capillaries
Secretion - This is the movement of substances from the peritubular capillaries into the lumen
Describe how the structure of the glomerular filter influences the filtration of substances
Between the glomerular endothelial cells, there are pores present referred to as fenestrations. The Bowman’s epithelial tubual cells are known as podocytes. They have process called Pedicel and between the pores there are gaps known as slit pore.
The pores between the endothelial cells or the fenesrations are the first layer whcih needs to be passed by filtrate. These fenestrations habe a diameter of around 60-70nm therefore there is a size restriction of a mw of 70kDa. These endothelial cells are also covered in negatively charged glycoproteins which repel anionic proteins. This thus neans that there is both a size and a charge restriction. small plasma proteins can pass thtough this layer
The second layer of filtration is the basement membrane which is the later between the flomerulus and Bowman’s capsule, It is composed of negatively glycoproteins which discourage filtration for small plasma proteins including plasma protein albumin. This does not allow any plasma proteins to pass throgh
The third layer is formed of podocytes which encircle the glomerulus. These are Long foot-like processes are separated by gaps called slit pores, through which the glomerular filtrate moves. The podocytes are also negatively charged so there is further restrictions to filtration fo plasma proteins
Define glomerular filtration rate (GFR) and explain the factors influencing GFR
The Glomerular filtration rate is the rate at which filtrate is produced from flowing blood through the glomerulus per unit time
GFR is influienced by the filtration coefficient and the Net filtration pressure
GFR = Kf x Net filtration pressure
The Kf itself consideres 2 factors: Glomerular surface area x Glomerular capillary permeability. Under normal Physiological conditons, Kf is relatively constant as those values do not regularly change and so Kf does not play a role in daily regulation of GFR.
A decrease in Kf can be attributed to an increase in thickness of the glomerular capillary membrane due to hypertension or diabetes , this means that glomerular permeablility(On of the parameters) also decreases
Net filtration pressure is determined by Physical forces also known as STARLING FORCES which drive the movement of fluid between plasma and the bowman’s capsule.
The starling forces are:
Glomerular Capillary hydrostatic pressure
Plasma-colloid osmotic pressure oncoic pressure
Bowmans capsule hydrostatic pressure
Bowmans capsile colloid osmotic pressure
Describe the processes involved in autoregulation of renal blood flow
Autoregulation is a maintenance of a constant renal blood flow and glomerular filtration rate over the mean arterial pressure. It is regarded as a protective mechanism against significant changes in blood pressure which could impact urinary excretion thus cause damage
The kidney can auroregulate quite rapidly to adjust to changes in blood pressure by adjusting the diameter of the afferent arteriole as it is myogenic( Has the ability to respond to stretch by contraction and resist the stretch of Vascular walls).
Vasoconstriction counteracts raised blood pressure by bringing about a reduced bood flow to the glomerulus. The maclua densa cells deect changes in fluids flowing through the ubes and secrete vasoactive chemiclas to dilate/contract blood vessels
Describe the Starling forces
The starling forces are the physical forces which drive the movement of fluids between the plasma to the bowman’s capsule
Hydrostatic pressure is the pressure exerted by a fluid at rest on a semi-permeable membrane. The movement of fluid across the membrane occurs from high hyrostatic pressure to low hydrostatic pressure. Glomerular capillary hydrostatic pressure is the pressure exerted by blood within the capillaries on the filter
Osmotic pressure is the pressure applied to a fluid at rest in order to prevent the inward flow of water through passive diffusion or osmosis via the membrane. A greater application of pressure, would be required to stop a high osmotic pressure. This means that the movement of water goes from a low osmotic pressure to a high osmotic pressure
Net filtration pressure is the difference between forces which favour filtration and oppose filtration.
List the 3 main methods to estimate the Kisney function, and include their appropritae use in defining renal function
1st, the Cockroft Fault equation which takes into account gender, age and weight of the patient
Another way is the Chronic kidney disease Epidemiology which refers i the body surface of an average adult, There are some restrictions however for example it should not be used in childre, malnourished patients or in pregnancy,
The final way to estimate kidney function is woih the Modification in Diet in renal diseae formula which oversetimates eGFR in the elderly
Review the transport processes in the movement of solutes and water across the membranes
Water and solutes move across the membranes during the processes of reabsorption and secretion
Hydrophillic molecules pass through membranes via channel or carriers
One of the way solutes and water may move is by diffusion down a concentration or electrochemical gradien across a membrane, and this can either be simple or facilitated.There are 2 ways diffusion can occur: Transcellular(Across the tubular cell), or paracellular through tight junctions.
The transport maximum is where the capacity of the carrier is exceededm it is the highet rate a substance can be transported per unit of time
Bulk flow is the moecment of wter solutes together in bolk as a single unnit in contrast to seperate diffusion of different solutes.
Describe The PCT handling of Na+,K+,H+,HCO3-, amino acids, glucose and urea by either active or passive reabsorbtion
All solutes are dependent on the action of the Na+/ K+ ATPase. In terms of secretion in the PC, there is a range of organic acids and bases which go into the PCT from the peritubular capiliary which mainly move bile salts. uric acid, diuretics etc and organic cation transporterrs which move adrenaline, noradrenaline and dopamine aswell as Opiods.
Na, Cl, K, HCO3, Glucose, water, amino acids and urea.
Sodium and Potassium move via the Na/K ATPase. The movement of Sodium causes a decrease in intracellular tubular cell sodium concentration, which causes a gradient to form between the tubular cell cytosol and the tubular lumen. As a result of this gradient, the Sodium moves into the tubular cell from the tubular lumen via a Sodium/H antiporter.(This causes secretion of H into the tubule lumen by secondary active transport).
This Sodium/Hydrogen antiporter is also involved in the movement of bicarbonate ions. In the tubular lumen, the Hydrogen meets HCO3- to form bicarbonate which dissocaites into H2O And CO2 which will diffuese via passive diffusion ino the tubular cell. They then go onto react in a reverse process(so form H2CO3 and then dissociate to form HCO3-) which is present in the tubular cell now. This will go to be reabsorped by a Na/HCO3- symporter. This is active reabsorbtion
Glucose is also transported bia a SGLT-2 symporter with Sodium.
Water primarily moves through tight munctions betwee the tubular cells, and waer channels in he membrane. It is aideed by the concentration gradient created by the Na movement. This is similar to urea
Calcium, Cl-, K+ and some sodium ions can be reabsorbed through paracellular transport
Describe the early DCT handling of Na+,Cl-,K+, and note its impermeability to water
The early DCT absorbs Na, K and Cl ions but is virtually impermeable to H20 and Urea.
Sodium and Chlorine move through to the Tubular cytosol from the lumen via a Symporter.
Sodium leaves into the interstitial fluid and then into the peritubular capillary by a Na/K ATPase, and Chlorine leaves via a membrane channel
Describe the Late DCT and collecting duct handling of Na+,K+,Cl-,H+,HCO3, and H2O. Note that the transport of Potassium, Hydrogen and HCO3- is dependent on the cell type
The late DCT and collecting duct are composed of Principal P cells and intercalated I cells.
The P cells reabsorb sodium ions and secrete Potassium ions, whereas the I cells reabsorb K and HCO3- and secrete H ions
Bicarbonate ions are absorbed by a transporter, and K are reabsorbed by a channel. The H are secreted into the lumen by aldosterone stimulated H secretion and By a K/H ATPase and a H transporter
Describe the actions of aldosterone and ADH on solute and water transport in the late DCT and collecting duct
Aldosterone is secreted by the Adrenal cortex and it increases Na+ and water reabsorption with accompanying Potassium secretion
It increases the expression of Sodium, potassium ATPase and the Sodium influx and Potassium efflux channels
ADH works to increase the permeability of the the late DCT and CD which increases the reabsortion of water via V2 receptors. It does so by increasing the expression of aquaporin water channels
