Genitourinary Flashcards
What are the functions of the kidneys?
- Filter the blood to remove waste
- Regulate water, salt, acid-base
- Regulate blood pressure
- Produce hormones and enzymes
What are the main components of a nephron, and what are their functions?
Renal corpuscle- mainly functions in filtrration
Proximal convoluted tubule: main function is the reabsorption of 65% of filtrate
Loop of henle: Main function is water retention
Distal convoluted tubule: Main function is salt, pH level adjustment
Collecting duct: main function is water retention
Describe the overall structure of a renal corpuscle
Loops of capillary fed from an afferent arteriole, and drained by an efferent arteriole. Covered with a layer of epithelium and an epithelial capsule.
Has a vascular pole where vessels emerge, and a urinary pole where the PCT emerges
Describe the glomerular filtration barrier
Made up of three major components- the endothelial layer, the glomerular basement membrane and podocytes
Makes up a physical and charge barrier
Restricts the movement of cells, albumin and other large proteins
Describe the glomerular capillary endothelium
- Contains holes to permit the movement of small molecules through
- Covered with negatively charged glycocalyx to repel -vely charged proteins in the blood
Describe the glomerular basement membrane
Thick, formed from collagen and proteoglycans
Has a dense core and thinner outer layers
Acts as a physical and charge barrier
Describe podocytes and the slit membrane
Podocytes are adherent to the GBM, with primary processes and interdigitating processes coming off from each. They form slits linked by a slit membrane and are also covered in negatively charged glycocalyx
The slit membrane is a fine filter also covered in glycocalyx.
What are mesangial cells?
Smooth muscles packed into the capillary tuft that support the shape of the tuft
They produce ECM and are involved in scarring (glomerulosclerosis)
What is the juxtaglomerular apparatus?
JG cells: Modified smooth muscle cells in the wall of the afferent arteriole responsible for secreting renin.
Macula densa cells sense Na+ in filtrate conc.
Also extraglomerular mesangial cells
In response to high Na, the afferent arteriole will vasoconstrict. At lower Na, renin is released
What is the PCT and what are its main functions?
A tube of cuboidal epithelium with a large brush border for increased transport
Performs pinocytosis
Has lateral processes and infoldings to increase SA
What is the thin limb of the nephron like?
Thin squamous epithelium with a role in water reabsorption. The nuclei bulge into the lumen
What are distal tubule cells and how are they arranged?
They are cuboidal, with interdigitating lateral processes and infoldings, like proximal tubule cells. They have no brush border as there isn’t as much to reabsorb. They don’t perform pinocytosis but do fine-tune the salt, pH and concentration of the urine.
What is the collecting duct and how is it organised?
It is the final modifier of water, salt and pH of urine
Cells go from cuboidal to columnar
What is the macroorganisation of the kidney?
Kidney is surrounded by a renal capsule
Made up of lobes, with cortex on the outside and medullary pyramids on the inside
Apex of medullary pyramids called renal papillae
Papillae enveloped by calyces
Cortex contains medullary rays due to nephrons
What parts of the nephron make up each part of the kidney?
Cortex is renal corpuscles and portions of the P and DCTs
Medulla is collecting ducts and loops of henle
Medullary rays are straight bundles with collecting ducts and P//DCTs going to and from the medulla. These form the centre of a lobule
What defines a lobule?
Collecting duct in the middle with nephrons surrounding it
What is the vascular supply of the kidney?
More superficial nephrons: Renal artery –> Interlobar artery –> arcuate artery –> interlobular artery –> afferent arteriole –> tuft –> efferent arteriole –> peritubular capillaries –> interlobular vein –> arcuate vein –> interlobar vein –> renal vein
Longer nephrons: Renal artery –> Interlobar artery –> arcuate artery –> arterial vasa recta –> capilary beds around loops –> venous vasa recta –> arcuate vein –> interlobar vein –> renal vein
What is the structure of the ureter and bladder?
Lied with transitional epithelium, which is folded to allow expension
Mucous membrane for lubrication, protection
Elastic CT
Smooth muscles for peristalsis
Adventitia for blood and elasticity
How does the lining of the urethra change?
Starts out transitional epithelium, as in the bladder, then onto stratified columnar and stratified squamous as it leaves
What are the main posterior wall muscles?
Quadratus lumborum
Iliacus
Psoas major
Describe quadratus lumborum
Origin is iliac crest, inserts rib 12 and transverse processes of L1-4
Helps in brething and bending
Innervated by ant. rami of T12-L4
Describe Iliacus
Origin is iliac fossa, inserts lesser trochanter with psoas
Hip flexion
Innervated by fem nerve
Describe psoas
Originates T12-L5 vertebral bodies and discs, inserts lesser trochanter with iliacus
Sit ups, bending
Innervated by ant. rami of L1-4
What vessels supply and drain the abdominal wall?
Aorta branches off to give 5 lumbar arteries- like the intercostals
Veins more complex
Why are veins more superficial than arteries? What is the exception with this?
Superficial to prevent clamping from arteries
IVC is deep to aorta, which means it can be compressed on its left side where it crosses over after forming the left common iliac.
Describe the supply/drainage of the kidneys
Located on top of quad lumborum
Right kidney lower- behind R12 in comparison to Left kidney behind R11-12. Ureters exit at L1/2
Supplied by renal veins and arteries, divided into upper and lower poles
Arteries come off at L1/2, with right being longer than L
Renal veins drain to IVC at L1/2, with left being 3x longer than right
Supplied by renal plexus, pain referred to flank
Lymph is para-aortic nodes at L1/2
Describe the placement and supply of the ureters
Exit the kidneys at Li
Extend over the surface of psoas in line with transverse processes of lumbar spine. Crosses bifurcation of common iliac artery. Enters bladder at the trigone
Can be constricted at the junction of the ureters with the renal pelvis, or as they enter the wall of the bladder
Sup 1/3 supplied by renal artery, vein and plexus
Mid 1/3 supplied by gonadal/iliac artery and vein
Inf 1/3 supplied by sup vesical artery and vein, and hypogastric plexus
Pain referred from loin to groin
Lymph is para-aortic at L1/2 to iliac nodes
What is the structure of the bladder and what is its supply?
Has a partial covering of peritoneum on its upper surface, lined with transitional epithelium. Muscular coat of smooth muscle called detrusor, and a sphincter vesicae . As it fills it rises into the suprapubic cavity
Supplied by sup and inf vesical arteries and drained by vesical plexus into the internal iliac
Nerves from inferior hypogastric plexus. Symp. is sacral splachnic nerves (L1/2) and para is pelvic splachnic.
Pain referred to suprapubic region
Describe the trigone
A triangular smooth area at the base of the bladder, with no rugae. Ureters enter and urethra exits at its points. In between uteric openings is the interuteric crest, which is the least mobile and most easily aggravated area.
Describe the regions of the urethra in males vs females
Females: Superficial and deep regions
Males: pre-prostatic, prostatic, membranous and spongy areas
Lymph drainage to the internal iliac nodes
What are the nerves of the lumbar plexus?
L1 gives iliohypogastric and ilioinguinal nerves
LI and 2 gives genitofemoral
L2 and 3 gives lateral femoral cutaneous nerve
L2-4 gives femoral and obturator
Describe the iliohypogastric and ilioinguinal nerves
Both from L1
IH senses lateral gluteal and pubic skin, movement of transverse abdominis and internal obliques
II senses medial thigh, root of penis or labia majora, movement of transverse abdominis and internal obliques
Emerge at lateral border of psoas and run over QL. Pierce TA
Ilioinguinial pierces internal oblique to enter inguinal canal and accompany spermatic cord through the superficial inguinal ring
Describe the genitofemoral nerve
Comes from L1/2
Senses scrotum or mons pubis and skin of sup ant thigh
Moves cremasteric muscle
Emerges on top of psoas
Enters spermatic cord to innervate cremaster muscle and innervate genital skin
Describe the lateral femoral cutaneous nerve
Comes from L2/3
Senses skin on ant lat thigh
Emerges from lateral psoas, descending across iliacus and passing under the inguinal ligament laterally
If compressed it causes bernhardt roth syndrome which is numbness of the outer thigh
Describe the femoral nerve
Comes from L2-4 Senses ant thigh and med leg Motors pectinius, iliacus and anterior compartment Emerges from inf lat border of psoas Runs between iliacus and psoas Passes under inguinal ligament to thigh
Describe the obturator nerve
Comes from L2-4
Senses skin on med thigh
Moves obturator externis and medial compt of thigh
Emerges from lower med border of psoas, passing behind common iliac arteries and lateral to internal iliac and ureters
Runs along the pelvis to exit via the obturator foramen through the obturator canal
What are some tricks for remembering the nerves of the lumbar plexus?
there are 2x1, 2x2 and 2x3 contributed nerves
Lateral femoral goes to the ASIS
Genitofemoral is the only one on top of psoas
Femoral is big
Obturator is the only one medial to psoas
Where is our water composition from in the body?
Fat holds less water than regular body tissue, so women/overweight/elderly people have the least water%, and babies have the most
The water is held mostly in the ICF, but somewhat in the ECF, where it is split between ISF and plasma
What is the difference between osmolarity and osmolality?
Osmolality is the number of osmotically active particles per unit weight of solvent. Units are osmoles/kg
Osmolarity is the number of osmotically active particles per litre of solution. Its units are mOsmol/L
What is tonicity?
The osmotic pressure that a solute exerts across a cell membrane, causing movement of water
It accounts only for osmotically active impermeable solutes, rather than all. It isn’t readily measurable.
What is the difference in cell result if you put a cell in hypotonic, isotonic or hypertonic solutions?
Hypotonic make cells swell
Isotonic makes cells stay the same size
Hypertonic makes cells shrink
Describe the Gibbs-Donnan equilibrium
Charged particles separated by semi permeable membranes can fail to distribute evenly in the presence of a non-diffusibe ion.
IE if you have 10 -ve and 10 +ve ions on one side, and the same number on the other, but add 5 non-diffusible -ve ions on one side
1. Negative ions move down their conc. gradient towards the large ions, as they are relatively less concentrated. Positive ions follow the negative to balance the charge.
The competing electrical and chemical gradients mean that there is a voltage gradient at eq- the protein side is more -ve
The water will also flow to the protein side due to oncotic pressure
How does the cell address the gibbs-donnan equilibrium?
- They pump out osmotically active Na+ using the Na+/K+ATPase, meaning that the K+ and proteins inside can balance the Na+ outside, making the ISF and ICF isotonic.
What happens in hypotonic and hypertonic ECF osmolality?
In hypotonic, the cells will swell- very dangerous for the brain
In hypertonic, the cells will shrink- this is critical for survival and is regulated by altering water levels
What is ECF volume?
The volume of body fluid- it depends primarily on the Na+ balance. It’s less maintained
How can ECF volume be changed due to increased Na+ consumption?
Changes in starling’s forces in the plasma can lead to movement of fluid into the interstitial space, causing edema. Additionally, a higher Na+ intake over a few days causes salt excretion to lag, but water gain due to retention to maintain osmolality at increased Na+ levels.
There is a transient increase in osmolality followed by increased Na+ excretion and increased thirst. Osmolality returns to normal but at the expense of a larger ECF volume. This continues while the high Na+ diet continues. The volume returns to normal if less Na+ is ingested or a diuretic is given
As ECF increases, BP increases and natriuresis increases
What is the difference between glucose, saline and free water effects on the body?
Free water is cleared rapidly, saline very slowly
Glucose is metabolised to water, so infusing it will dilute all compartments
Isotonic saline temporarily expands the extracellular compartment
Hypotonic saline expands the intracellular compartments
What is the overall difference between osmolality and ECF volume?
Osmolality is thightly regulated by renal water handline, controlled by ADH
ECF volume is regulated variably by Na+ handling, controlled by the RAA system
What is the difference between starling forces in normal and kidney capillaries?
The glomerulus has a very leaky capillary tuft. There is a 10mmHg net filtration pressure, meaning that 20% of plasma volume is filtered.
How is the glomerular filtration rate regulated?
Mainly via changes in glomerualr BHP
- This is due to renal autoregulation keeping GFR constant over a wide range of blood pressures. It involves a feedback mechanism causing either dilation or constriction of the afferent arteriole, or constriction of the efferent arteriole
How can the autoregulation of glomerular BHP change the GFR?
Constriction of afferent results in decreased BHP and decreased GFR
Dilation of afferent results in increased BHP and increased GFR
Constriction of efferent results in increased BHP and increased GFR
What are the five mechanisms of renal autoregulation?
- RAA system causes constriction of efferent arterioles for increased GFR
- ANP causes dilation of the afferent arterioles for increased GFR
- SNS causes constriction of the afferent arterioles for reduction in GFR
- Myogenic stretch offsets pressure increases to stabilise GFR
- Tubuloglomerular feedback constricts afferent arterioles to decrease GFR
How does tubuloglomerular feedback work?
High GFR –> more Na+ past the macula densa –> paracrine signals –> afferent arteriole constricts
How does the RAA mechanism work on capillaries?
Low GFR –> less Na+ past the macula densa –> paracrine signals –> JG cells release renin –> angiotenin II –> constriction of efferent arteriole. ALSO –> aldosterone released –> Increased Na+ reabsorption –> increased BV
What happens when blood pressure drops in the glomerulus?
Decreased BHP –> decreased GFR–> Decreased Na+ to macula densa –> increased renin and ang II –> constriction of efferent arteriole
Myogenic response shows decreased stretch, and tubuloglomerular feedback combines with this signal to reduce the resistance of the afferent arteriole to increase hydrostatic pressure
What is the function of the proximal tubule?
Major site of filtrate reabsorption- takes up 2/3 of the water and ions, 100% of the glucose and 90% of the bicarbonate. Can transport things along the transcellular pathway in primary (active, atp transport) or secondary (co/anti) transport or in paracellular.
How are most solutes taken back up into the blood from the PCT?
Na+ gradient is established by NA/K-ATPase and an Na+ symporter takes something along its own concentration gradient. Water follows the charge by paracellular osmosis, sometimes brining things via solvent drag
How is bicarbonate reabsorbed in the PCT?
First, it is converted to carbonic acid, which is the converted by carbonic anydrase on the luminal cells to H2O and CO2, which freely diffuse. Once in the cytosol, CO2 is rehydrated, and taken back into the blood by basolateral transporters
How is bicarbonate produced in the PCT?
Glutamine is metabolised to ammonium and bicarbonate. Ammonium is secreted into the lumen by an Na/NH4X. HCO3- is transported into the blood/ Increases in ECF acidity increases HCO3- production
What is fanconi syndrome?
Impaired ability of the PCT to reabsorb HCO3-, Pi, amino acids, glucose and small proteins, resulting in these being excreted
How is chloride reabsorbed in the late PCT?
It’s concentrated in the late tubule due to everything else being taken out already
It moves down its concentration paracellularly via leaky tight junctions, and the charge difference brings more Na+ with it
How are drugs secreted into the PCT?
Organic anion and cation secretion is important for drug, and other xenophobic agents from the blood.
They are transported into the cells by electrogenic transporters, and then out via antiporters
What is the overall function of the loop of henle?
Produces urine that is more concentrated or more dilute than plasma/ Concentration can vary from 50-1200 mOsm/kg water, and volume varies from 0.5 to 20L per day
What are the main methods of transport of each major solute in the PCT?
Glucose via Na+ cotransporter Na+ via Na+ transporter Cl- paracellular K+ solvent drag H2O paracellular HCO3- via specific transport
How does water get reabsorbed in short loop nephrons?
In the thick ascending limb, Na2ClK transporters push Na+ into the ECF and K+ is removed into the tubule via ROMK transporters. The tight junctions are impermeable to water. This causes a steep Na+ hypertonic interstitial fluid. As the thin descending limp is permeable to water, water is extruded from the TDL and taken up by the ascending vasa recta. The descending vasa recta lost water during the descent, so the concentration gradient draws water out of the loop and into the vessels
What is the function of the early DCT?
Fine tuning the salt balance. This area is impermeable to water and actively pumps NaCl from the tubule into the ISF
What is gittleman syndrome?
A mutation in the NACL transporter resulting in NACl wasting, hyperaldosteronism and hypokalemic alkalation.
What are the two cell types in the late DCT and what are their functions?
Principal cells cause the reabsorption of Na_ via the ENaC, driving K+ secretion due to the electrical gradient
If this K+ channel is inhibited as in Liddle’s syndrome, then it will cause increased ECF volume and hypertension
Diuretics cause K+ secretion by delivering more Na+ to the tubule, which can cause hypokalemia and arrhythmias
Aldosterone causes the increased functioning of ENaC and induces more of them (late phase)
Intercalated cells usually secrete H+ for the reabsorption of HCO3-, and those that aren’t used give urine its acidic pH
What is the overall mechanism of acid regulation?
CO2 taken in via metabolism and expired in breath is converted to HCO3-, which is produced by the kidney, and H+, which is produced by metabolism and diet, and removed by the kidney. This forms a buffer system
As a result, the HCO3- is given into the blood both by being reclaimed from tubular fluid, and from production in the kidney. H+ is removed from the blood to be secreted
How can ammonium help with acid extrusion?
As the amount of H+ able to be secreted is limited, H+ can be attached to NH3 in order to be secreted into the urine as NH4+
How is water reabsorbed in the collecting duct?
Depends on ADH- at high levels, many preexisting aquaporin 2 channels are inserted into the luminal membrane, allowing water to pass through the duct and back into the plasma. In its absence, water remains in the channels.
How is the long loop of henle able to return water to the blood?
The passive hypothesis
Urea becomes very high in the cortical collecting duct when ADH is present, due to H2O reabsorption.
ADH increases urea and H2O permeability in the inner medulla collecting duct, allowing Urea and H2O to mvoe into the interstitium. This decreases the relative concentration of Na in the medulla.
NaCl moves out of the tip of the loop and into the interstitium by osmosis. The countercurrent by the vasa recta allows the osmotic gradient to carry water away as in the short loops.
If ADH is low, this does not happen, then interstitial urea may be above tubular urea in concentration, causing washout.
What is the process that occurs when the body is dehydrated?
Water deficit leads to increased ECF osmolarity which is detected by osmoreceptors. This causes increased ADH secretion from the posterior pituitary, increased H2O permeability in the collecting ducts, increased H2O reabsorption and decreased waste of H2O. Negative feedback then turns this process off.
Where is ADH formed and released?
Formed in the hypothalamus, released from post. pituitary
Describe the mechanism of ADH release
Osmoreceptors in the supraoptic and paraventricular nuclei sense high osmolarity. The medullary vasomotor centre detects decreased volume and inputs the info to the hypothalamus
Osmoreceptor neurons are cross linked. When cells shrink, they open up gates to trigger ADH APs
What are the stimuli that cause ADH release?
Increased plasma osmolarity by 1-2%
Decreased circulating volume by 7-10%
Non-physiological stimulation including pain, stress.drugs, cancer, pulmonary and CNS disorders
Alcohol inhibits ADH release
What is centralvs nephrogenic DI and how do you tell the difference?
Central is inadequate ADH being secreted, resulting from a problem with the hypo. or PP due to tumor, infection and injury- rarely hereditary. It can be treated by giving ADH
Nephrogenic occurs when the collecting tubule is insensitive to ADH, resulting in an inability to concentrate urine. It can be due to a congenital or inherited defect in V2 receptors or Aquaporin 2
Can’t be treated
Difference can be told by depriving patient of water and then giving supplementary ADH
If urine becomes concentrated it’s central, if not it’s nephrogenic
What is SIADH?
Syndrome of inappropriate ADH secretion
Higher than normal ADH levels, so patient retains unncecessary water. Lower urine osmolarity. Can cause hypo-osmolal state which can cause death etc.
Cuased by injury, tumor or drugs
Water intake must be restricted
What factors promote renin secretion?
Low afferent arteriolar pressure or macula densa NaCl delivery
High sympathetic nervous activity
What are the consequences of increased renin secretion?
Angiotensin I becomes angiotensin II, which causes increased aldosterone, vasoconstriction, increased Na+ reabsorption, thirst, ADH and decreased renal blood flow, but maintaining GFR
It also causes vasodilation at AT2 receptors
What is the result of increased aldosterone?
Increased Na+ reabsorption in the collecting duct,resulting in increased water intake via the paracellular route
How do you calculate pH/[H+]?
pH is the log10 of [H+].
[H+] is 10^pH
What is the difference betwen acidaemia/alkalaemia and acidosis/alkalosis? What is the normal pH level?
In the body, pH between 7.35 and 7.45 is normal
Adicaemia is a pH below 7.35
Alkalaemia is a pH above 7.45
Acidosis is a condition usually causnig pH below 7.35
Alkalosis is a condition usually causing pH above 7.45
What does a buffer do? What are some examples?
A buffer minimises pH change due to its ability to absorb or exude H+ ions. This is only temporary
pH = pK + log ([base]/[acid]) so when base and acid are equal, pH = pK
Examples include bicarbonate, some proteins, such as albumin, and some chemicals, such as ammonnia
What is the henderson-hasselbach equation?
For the buffer HCO3-
pH = 6.74 + log (HCO3-/pCO2)
How does the respiratory system help to regulate body pH?
The increased CO2 pressure causes acidosis, and decreased CO2 causes alkalosis.
Low pH also causes the stimulation of ventilation.
What effects does a change in pCO2 have on the buffer balance?
Normally, the relative concentrations of pCO2 and bicarbonate are equal. In respiratory acidosis, pCO2 increases, and in respiratory alkalosis, pCO2 decreases
What happens in acute, life-threatening status asthmaticus?
The patient becomes unable to ventilate properly, and pCO2 increases vastly, causing respiratory acidosis
What happens in hyperventilation?
There is increased expiration of CO2, resulting in reduced pCO2 and respiratory alkalosis. This is also similar to how mild asthma attacks occur, as the patient experiences an increase in ventilatory drive without respiratory failure
What is metabolic acidosis and what can cause it?
Decreased availability of bicarbonate (likely due to increased acid production that exceeds renal excretion). The bicarbonate is used up as a buffer, and the acid concentration builds.
Can be caused by increased acid production in terms of lactic acidosis (due to poor tissue perfusion), or diabetic ketoacidosis.
May be due to decreased acid excretion, in terms of renal failure and renal tubular acidosis
Can be due to bicarbonate loss, such as in severe diarrhoea or ileostomy
What is metabolic alkalosis?
Increased availability or production of HCO3- and subsequent decrease in acid concentration. Often due to loss of acid due to vomiting, extra ingestion of sodium bicarbonate etc. When the equation shifts towards the acid side, the unlimited CO2 and H2O can form more HCO3-
What are the hallmarks of each alkalosis/acidosis condition?
Metabolic alkalosis has high pH, high bicarbonate and normal pCO2
Respiratory alkalosis has high pH, normal bicarbonate and low pCO2
Metabolic acidosis has low pH, low bicarbonate and regular (early) or low (late) pCO2
Respiratory acidosis has low pH, regular bicarbonate and high PCO2
What is respiratory compensation in metabolic acidosis?
Low pH stimulates ventilation, causing a drop in pCO2. This partially returns pH to a more normal value
What role do the kidneys play in acid-base balance?
They produce new bicarbonate, they excrete NH4+ and TA acid, and allow bicarbonate to be reabsorbed
This is called net acid excretion- amount of NH4+ excreted, amount of TA excreted, minus the HCO3- excreted x the volume
How are the kidneys involved with HCO3-?
They reabsorb it along with Na+, using carbonic anhydrase to convert it to CO2 and H2O, before taking it in and using the same enzyme to change it back
How is H+ secreted in the distal tubule and collecting duct?
It may be attached to NH3 formed from glutamine, although most NH3 is reabsorbed in the TAL In the collecting duct, diffusion trapping places H+ on free NH3, allowing it to be secreted.
How does the kidney respond to acidosis?
It increases HCO3- and H+ transport along the nephron
It increases its availability of urinary buffers as well as increasing ammoniagenesis.
This causes generation of bicarbonate, so even though CO2 might have increased in respiratory acidosis, the HCO3- becings to increase, pulling the pH back to a more reasonable level
What is a clinical example of renal compensation?
Eg. A 60 year old who has been smoking for 40 years- has a normpal but low pH, a high pCO2, high bicarbonate.
What happens to renin secretion in each kidney if one artery becomes obstructed?
In the obstructed kidney, flow rate decreases and so does perfusion pressure, triggering the release of renin. This goes on to cause increased angiotensin II, causing an increased in systemic blood pressure. Because of this, the left kidney decreases its production of renin
What can trigger the release of aldosterone?
Increased levels of angiotenin II and increased K+
How does aldosterone act in the body?
It binds to mineralocorticoid receptors and increases the production of ENaC channels to be inserted into the luminal side of the principal cells, absorbing more Na+ and water into the blood
What can occur due to hyperaldosteronism?
High blood pressure due to increased retention of salt and water
What happens if the function of aldosterone is 100% lost?
Other reflexes to Na+ deficiency can be used, such as a reduction in GFR
What can cause increased vs. decreased Na+ reabsorption?
Increased: RAA system, SNS activity, ADH
Decreased: ANP, decreased RAA and SNS, dopamine and prostaglandins
What is ANP?
Produced by atria due to increased filling pressure and stretch. It decreases Na+ reabsorption in the distal tubule and outer medullary collecting duct by blocking ENaC channels
It also inhibits the release of aldosterone and renin, and vasodilates the afferent arteriole to increase GFR
What are the processes that occur when the body gets dehydrated?
Increased osmolarity leads to osmotic receptors sensing it and causing release of ADH, which acts on the V2 receptor to cause increased H2O retention
Decreased blood volume triggers ANP
Decreased blood pressure triggers baroreceptors to increase SNS activity
What is the main result of kidney failure and what are its two subtypes?
Low GFR
Subtypes are acute kidney injury, and chronic kidney disease
What are the blood tests that can indicate kidney failure?
- Urea in blood
- Creatinine in the blood- if the kidney can’t excrete it the levels will rise.
What extra-renal factors will affect plasma creatinine?
Age- older people have decreased muscle mass and so less creatinine
Weight- more muscle mass means more creatinine
Gender- men have higher muscle mass
What is eGFR?
Estimated glomerular filtration rate- it accounts for creatinine as well as age and sex, taking into account muscle mass- however, it only works for patients with stable creatinine, as well as not working for those with unusual muscle mass- eg. amputees.
What is acute kidney injury and what can be its categories of cause?
- It's a sudden and rapid reduction in GFR that is usually reversible. It's mostly due to non-renal causes Injury can be: - Pre renal - Renal - Post Renal
What can cause pre-renal kidney failure?
Low blood pressure (as blood is redirected to more essential organs) or not enough blood to the kidneys, due to dehydration, septic shock, haemorrhage, cardiogenic shock or severe renal artery stenosis
What are the examination symptoms of the different causes of pre-renal kidney failure?
Low BP- postural drop
Dehydration- Low JVP, decreased tissue turgour
Sepsis- fever
Haemorrhage- bleeding
Signs of cardiogenic shock- heart failure/pulmonary oedema
Low initial urine output
What do test and treatments find in pre-renal failure? What are possible consequences?
A high creatinite in the blood, as well as hyperkalaemia, high phosphate and potentially low calcium
Treat the underlying problem, such as rehydrating, antibiotics, treatment of haemorrhage, or ICU admission for consistent low BP
If it doesn’t get better, it can go on to acute tubular necrosis
What is acute tubular necrosis?
Consequence of untreated pre-renal kidney failure.
Needs to be treated by maintaining a norma BP and treating the underlying condition. If the kidneys get worse, dialysis can keep the kidneys alive while they heal, but is not a treatment in itself
Most get better
May show a polyuric phase- tubules aren’t able to concentrate the urine, so up to 20L a day may be produced
What is glomerulonephritis?
One of the causes of renal kidney failure (besides ATN)- due to inflammation of the glomerulus. It’s the main cause of acute kidney injury, due to vasculitis or infection
It presents with blood and or protein in the urine, and is diagnoses with renal biopsy
What are some post renal causes of kidney failure?
Due to blockage or squashing of post-renal structures. It can be due to kidney stones, tumour, prostate hypertrophy or urinary retention.
What is Chronic Kidney Disease and what can cause it?
It’s a gradual decline in renal function that is irreversible. It presents with elevated creatinine and urea, although urine output is normally usual.
It can be caused by diabetes, glomerulonephritis, and hypertension, among others
What are the symptoms of those with chronic kidney disease?
Usually none in the early stages, and are found on blood tests. Can sometimes have uraemia if the case is severe enough. Most common sign is hypertension, with oedema, pulmonary oedema and a raised JVP
What is uraemia?
Anorexia Nausea Vomiting Itchiness SOB Cold intolerance Swelling Seizures Coma
Why does chronic kidney disease present with anaemia?
The kidney makes erythropoietin, which makes the bone marrow produce RBCs. Kidneys in failure will not produce this correctly. However, this does not present for a while as RBCs have a life of about 3 months
How does chronic kidney disease present with bone disease?
The kidneys produce 1-hydroxylase, which transforms vitamin D into a useable form to allow Ca2+ and P to be used.
Phosephate is excreted less, there is a low vitamin D and a low calcium. there is also a high parathyroid stimulation due to low Ca2+ and high K+, resulting in excessive calcium resorption in the bones, fractures, extra-osseous calcification and vascular calcification (causing thrombosis and embolism)
What is concerning about high potassium in CKD?
The kidneys don’t excrete K+, causing arrhythmias. This can increase mortality
How is CKD treated?
Mainly by preventing failure from growing worse, and controlling its implications
What are the stages of CKD?
1- GFR slightly reduced
- GFR reduced, increased PTH
- GFR much reduced, decreased Ca2+
- GFR borderline, has anaemia, CV risk, high P, acidosis and hyperkalaemia
- GFR less that 15ml/min, presents with uraemia
What are the clinical presentation and problems that can be due to generalised parenchymal disease?
Haematuria Proteinuria Acute nephritic syndrome Nephrotic syndrome CKD Need to assess renal function
What are the clinical presentation and problems that can be due to collecting system abnormalities?
Present with infection, polyuria, renal colic and CKD
Assess renal function
