Describe how nitrates are used in management of angina
Angina happens when not enough blood gets through to the cardiac muscle. Nitrates dilate resistance vessels, including the coronary arteries supplying the heart, thus increasing the blood supply to the heart. The two main nitrates are glyceryl trinitrate (GTN) and isosorbide dinitrate. They are converted to nitric oxide via organic nitrate ester reductase, and the nitric oxide produced goes onto cause relaxation of vascular smooth muscle.
GTN and isosorbide mononitrate differ in terms of their pharmacokinetics. GTN has very high first-pass metabolism, meaning that if you try to give it orally, it will be broken down by the liver and you won't get much use out of the drug. Therefore, GTN is usually given by sublingual spray or transcutaneous patch, or by IV in severe cases. Isosorbide mononitrate has a lower first-pass clearance and can be given orally.
Another thing to keep in mind with nitrates is that they can lose their effectiveness quickly. If nitrates are used constantly over 24 hours, they lose their effect- a process called "tachyphylaxis." Therefore, if people are using transcutaneous GTN patches, the patches need to be taken off overnight.
Describe how antiplatelet agents, beta adrenoreceptor blockers,
thrombolytics and anticoagulants are used in the context of ischaemic heart
disease
This lecture basically covered emergency situations ("acute coronary syndromes"), including unstable angina, non-ST elevation acute myocardial infarction, and ST-elevation acute myocardial infarction (STEMI). (ST-elevation refers to a feature of the ECG tracing.)
Antiplatelet agents
Antiplatelet agents are drugs that block various actions of platelets. I've covered them here. Aspirin and clopidogrel (an ADP receptor antagonist) are good for inhibiting platelet aggregation on coronary plaques.
Beta-adrenoceptor blockers
Beta-blockers, as discussed here, reduce the contractility and rate of the heart. In turn, this reduces the heart's demand for oxygen so that it can make do with less oxygen than before. In acute coronary syndromes, beta-blockers help to limit the size of the infarct and reduce pain.
Thrombolytics
Thrombolytics (a.k.a. profibrinolytics) are good when urgent thrombolysis is needed (i.e. you need to get rid of a blood clot NOW, not prevent them from happening in the future). I have discussed them here.
Anticoagulants
Anticoagulants are good for preventing clots from happening in the future. One of the main ones that is used is low molecular weight heparin, which can prevent thrombotic and embolic complications of heart attacks. I have discussed these here.
Tuesday, April 9, 2019
Monday, April 1, 2019
Drug Management of Heart Failure
Describe the physiology of Na, K and H2O renal excretion, including the renin-angiotensin-aldosterone system
Describe the drug strategies to enhance Na and H2O excretion (ACE inhibitors, aldosterone antagonists)
ACE inhibitors, such as enalapril and captopril, work by inhibiting angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II. Since angiotensin II normally works on the arterioles to cause constriction and on the adrenal cortex to increase the release of aldosterone, inhibiting ACE causes vasodilation (and an increase in blood flow to the kidneys) and an increase in salt and water excretion (via the actions of aldosterone).
Angiotensin II and aldosterone can also be blocked directly. AT1 receptor blockers block the actions of angiotensin II (since AT1 receptors, confusingly enough, are the receptors for angiotensin II). These drugs tend to end with the suffix -sartan, such as irbesartan. Aldosterone antagonists such as spironolactone not only increase salt and water excretion, but also inhibit the myocardial remodelling that occurs during heart failure.
Describe the clinically important beta adrenoreceptor blockers
Beta-1 blockers can also be used to treat heart failure, as they can block cardiac modelling and also decrease the myocardial contractility (which in turn decreases the blood pressure). Furthermore, they can also slow the heart down, allowing more time for the ventricles to fill with blood (which is important in cases of diastolic heart failure). Most beta-blockers end with -olol, and include metoprolol and bisoprolol. Adverse effects of beta-1 blockers are mainly related to off-target activation of beta-2 receptors, and include bronchospasm (which is why beta-blockers tend to be avoided in people with asthma). There are also side-effects from having too much of a good thing, such as excessive slowing of the heart.
Describe the clinically important diuretics
I'll discuss diuretics in a later post, but essentially diuretics act on certain transporters in the tubule to decrease reabsorption and/or increase secretion of salts and water so that you pee more. The main types of diuretics include loop diuretics (e.g. frusemide), thiazides (e.g. hydrochlorothiazide), and aldosterone antagonists (e.g. spironolactone).
Describe how digoxin acts as antiarrhythmic agent and to increase cardiac contractility
Digoxin is an antiarrhythmic that is also used for heart failure. It works by blocking Na+/K+ pumps, thus reducing the gradients of sodium and potassium. Because it blocks the pumping out of sodium, it also has a downstream effect on Na+/Ca2+ exchangers, which bring in sodium to let calcium leave the cell. Because the Na+/Ca2+ exchangers are being affected, there is more intracellular calcium, which leads to more efficient contraction of myocytes and increased cardiac contractility.
Digoxin also has indirect effects on the heart via the vagus nerve. Digoxin stimulates the vagus nerve, causing an increase in parasympathetic stimulation and decreased heart rate. Therefore, digoxin is also good for treating supraventricular tachyarrhythmias (only the supraventricular ones as the ventricles don't get parasympathetic stimulation).
Even though digoxin can reduce heart rate, at toxic doses it can actually increase heart rate. Since digoxin blocks the Na+/K+ pump, there is a smaller potassium gradient and so less potassium leaves the cell during repolarisation. Therefore, the membrane becomes less polarised (i.e. less negative), making it easier to reach threshold during the next heartbeat.
Digoxin toxicity may also present with other symptoms, such as serious arrhythmias, nausea, confusion, and visual problems. Nausea and confusion are most commonly seen in elderly patients. Since digoxin relies a lot on the kidneys for excretion (~70% excretion via the kidneys), it is especially toxic in people with renal impairment. Digoxin is also especially toxic in people who are hypokalaemic, as potassium would ordinarily compete with digoxin for binding to the Na+/K+ ATPase.
Describe how nitrates may be used in heart disease
The actual mechanism of action of nitrates wasn't really discussed in this lecture, other than that they are vasodilators that can help in emergency situations by reducing afterload.
Describe the drug strategies to enhance Na and H2O excretion (ACE inhibitors, aldosterone antagonists)
ACE inhibitors, such as enalapril and captopril, work by inhibiting angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II. Since angiotensin II normally works on the arterioles to cause constriction and on the adrenal cortex to increase the release of aldosterone, inhibiting ACE causes vasodilation (and an increase in blood flow to the kidneys) and an increase in salt and water excretion (via the actions of aldosterone).
Angiotensin II and aldosterone can also be blocked directly. AT1 receptor blockers block the actions of angiotensin II (since AT1 receptors, confusingly enough, are the receptors for angiotensin II). These drugs tend to end with the suffix -sartan, such as irbesartan. Aldosterone antagonists such as spironolactone not only increase salt and water excretion, but also inhibit the myocardial remodelling that occurs during heart failure.
Describe the clinically important beta adrenoreceptor blockers
Beta-1 blockers can also be used to treat heart failure, as they can block cardiac modelling and also decrease the myocardial contractility (which in turn decreases the blood pressure). Furthermore, they can also slow the heart down, allowing more time for the ventricles to fill with blood (which is important in cases of diastolic heart failure). Most beta-blockers end with -olol, and include metoprolol and bisoprolol. Adverse effects of beta-1 blockers are mainly related to off-target activation of beta-2 receptors, and include bronchospasm (which is why beta-blockers tend to be avoided in people with asthma). There are also side-effects from having too much of a good thing, such as excessive slowing of the heart.
Describe the clinically important diuretics
I'll discuss diuretics in a later post, but essentially diuretics act on certain transporters in the tubule to decrease reabsorption and/or increase secretion of salts and water so that you pee more. The main types of diuretics include loop diuretics (e.g. frusemide), thiazides (e.g. hydrochlorothiazide), and aldosterone antagonists (e.g. spironolactone).
Describe how digoxin acts as antiarrhythmic agent and to increase cardiac contractility
Digoxin is an antiarrhythmic that is also used for heart failure. It works by blocking Na+/K+ pumps, thus reducing the gradients of sodium and potassium. Because it blocks the pumping out of sodium, it also has a downstream effect on Na+/Ca2+ exchangers, which bring in sodium to let calcium leave the cell. Because the Na+/Ca2+ exchangers are being affected, there is more intracellular calcium, which leads to more efficient contraction of myocytes and increased cardiac contractility.
Digoxin also has indirect effects on the heart via the vagus nerve. Digoxin stimulates the vagus nerve, causing an increase in parasympathetic stimulation and decreased heart rate. Therefore, digoxin is also good for treating supraventricular tachyarrhythmias (only the supraventricular ones as the ventricles don't get parasympathetic stimulation).
Even though digoxin can reduce heart rate, at toxic doses it can actually increase heart rate. Since digoxin blocks the Na+/K+ pump, there is a smaller potassium gradient and so less potassium leaves the cell during repolarisation. Therefore, the membrane becomes less polarised (i.e. less negative), making it easier to reach threshold during the next heartbeat.
Digoxin toxicity may also present with other symptoms, such as serious arrhythmias, nausea, confusion, and visual problems. Nausea and confusion are most commonly seen in elderly patients. Since digoxin relies a lot on the kidneys for excretion (~70% excretion via the kidneys), it is especially toxic in people with renal impairment. Digoxin is also especially toxic in people who are hypokalaemic, as potassium would ordinarily compete with digoxin for binding to the Na+/K+ ATPase.
Describe how nitrates may be used in heart disease
The actual mechanism of action of nitrates wasn't really discussed in this lecture, other than that they are vasodilators that can help in emergency situations by reducing afterload.
Renal Anatomy
I wasn't sure what to blog about next, so I wrote down all of the fields that we're studying (microbiology, anatomy, physiology, etc.) and let a random number generator pick for me. It picked the number corresponding to Anatomy, so I guess that's what I'll be blogging about now! (Also, I bombed a large proportion of the anatomy questions in the set of formative renal questions that we were given, so I guess I need the extra study...)
Describe the position and functional anatomy of the kidneys and ureters.
The kidneys are located in the abdomen, roughly between T12 and L3. The right kidney is slightly lower than the left kidney because it has been pushed down by the liver. The hilum of each kidney (where the blood vessels etc. join the kidney) is located at around L1-L2. Each kidney is surrounded by a layer of perirenal (or perinephric) fat, which is surrounded by a layer of renal fascia (a.k.a. Gerota's fascia), and then by a layer of pararenal (paranephric) fat.
Demonstrate the topographical relationships of the kidneys and ureters to other abdominal structures.
The kidneys are located laterally to the psoas muscle, and the ureters run along the front of the psoas. As the ureters enter the pelvis, they cross the bifurcation of the iliac arteries.
Describe the blood supply and innervation of the kidneys and ureters.
Blood supply
The kidneys receive blood from the renal arteries. Since both renal arteries arise from the aorta, and the aorta is on the left side of the body, the left renal artery is shorter than the right renal artery. The opposite is true for renal veins: the left renal vein is longer than the right renal vein. The left renal vein also receives blood from the gonads and adrenals (via the left gonadal vein and the left suprarenal vein respectively).
The ureters receive their blood supply from whatever structures are running close to them. The upper part of the ureters tend to receive blood from the renal artery, the middle part of the ureters tend to receive blood from the gonadal arteries and/or the aorta, and the lower part of the ureters tend to receive blood from the vesical arteries.
Innervation
The kidneys receive sympathetic innervation from T10 and T11 nerves (a.k.a. the lesser splanchnic nerves) and parasympathetic innervation from the vagus nerve. Sensory fibres follow the sympathetic fibres back to T10/T11, so kidney pain tends to be felt over those dermatomes. One important point is that nerves are not very important for renal function in general, but for renal blood flow. Aspects of renal function (how much salt and water to absorb, for example) tend to be controlled by hormones.
The ureters receive sympathetic innervation from T12 and L1, and parasympathetic innervation from the vagus and hypogastric (from S234) nerves. Just like with the kidneys, the sensory fibres follow the sympathetic fibres, so pain in the ureters is felt over T12 and L1.
Describe histology (microscopic anatomy) of the renal cortex and medulla including the renal corpuscle, proximal convoluted tubule, Loop of Henle, distal convoluted tubules, and juxtaglomerular apparatus and collecting tubules.
The outer region of the kidney is called the cortex, and is where the renal corpuscles and convoluted tubules are located. (Don't worry, I'll describe what they are and what they do in a bit.) The area deep to the cortex is the medulla, and contains the Loops of Henle and collecting tubules. There is, however, a bit of overlap between these two areas: the columns of the renal medulla contain the structures of the renal cortex, and the medullary rays of the cortex contain structures of the renal medulla.
Renal corpuscle
The renal corpuscle is made out of the glomerulus (a "knot" made out of arteries) and Bowman's space (the first part of the tubular system where urine is formed). Under the microscope, renal corpuscles basically look like a cluster of cells surrounded by a white ring (the Bowman's capsule). The renal corpuscle is the main site where filtration occurs (i.e. the blood gets filtered so that pretty much everything, except for large proteins, is pushed into the Bowman's capsule and the tubular system).
Proximal convoluted tubule
The proximal convoluted tubule is the first lot of tubules. The reabsorption of pretty much all glucose and amino acids occurs here, along with reabsorption of many other substances. Proximal convoluted cells are tall, columnar, and have a brush border to increase their surface area for reabsorption. Since the Na+/K+ pump is critically important for maintaining concentration gradients for reabsorption, proximal convoluted tubule cells have plenty of mitochondria to keep them topped up and ready to go.
Loop of Henle
The loops of Henle have two parts: a thin descending limb and a thick descending limb. The thin descending limb is more permeable to water than salt, whereas the ascending limb is impermeable to water but permeable to salt. The appearance of the Loops of Henle depends on whether you have a cross-section or a longitudinal section of the loop: cross-sections look like little circles, whereas the longitudinal sections look like long white stripes that are lined by cells. (I think. Histology isn't my strong point.)
Distal convoluted tubules and collecting duct
The distal convoluted tubule and collecting duct cells are similar to those of the proximal convoluted tubule, except that cells in the distal convoluted tubule and collecting duct tend to be cuboidal and less metabolically active than those in the proximal convoluted tubule. Both the distal convoluted tubule and the collecting duct are under hormonal control to change the amount of salts and/or water reabsorbed.
Another point of interest is the juxtaglomerular apparatus. The juxtaglomerular apparatus of the distal tubule interacts with the afferent arteriole by secreting hormones etc. to maintain filtration rate (see here).
Describe the histology of the ureter.
Ureters, like many other bodily tubes, have a mucosa, muscularis layers, and an adventitia. (However, unlike many other bodily tubes, they likely do not have a submucosa.) There are two muscularis layers: one is circular, and one is longitudinal. Together, the muscularis layers work to propel urine towards the bladder.
Describe the anatomy of the urinary bladder, its base and ureteric openings and its relationship to the overlying peritoneum.
The bladder is shaped kind of like an upside-down triangular pyramid. The urethra connects to the bladder at the inferior "point." The umbilical ligament, which is a remnant of an embryonic structure called the urachus, joins at the apex, which is the anterior superior "point." The ureters join at the posterolateral points and continue to pass through the wall of the bladder.
One point of interest is the bladder trigone, which is formed from the intermediate mesoderm of the urogenital septum. This is in contrast to the rest of the bladder, which is formed from the anterior part of an embryonic structure called the cloaca. The bladder trigone makes up part of the posterior wall of the bladder. The ureters open into the bladder at the upper lateral corners of the bladder trigone.
Describe the blood supply and innervation of the urinary bladder.
The bladder receives its blood supply from the superior and inferior vesical arteries. The superior vesical artery comes from the patent part of the umbilical artery, which in turn comes from the anterior division of the internal iliac artery. The inferior vesical artery comes directly from the internal iliac artery.
Like the ureters, the bladder receives sympathetic stimulation from T12 and L1. However, its parasympathetic innervation is only from the hypogastric plexus (S234). Both sympathetic and parasympathetic nerves activate muscles, but they activate different muscles: sympathetic stimulation causes the external urethral sphincter to tighten (and stop you from peeing), while parasympathetic stimulation causes the detrusor muscle (i.e. the bladder muscle) to contract, thus making you pee. Sensory information is a bit mixed: pain fibres follow the sympathetic nerves back to T12 and L1, whereas stretch fibres follow the parasympathetic nerves back to S234.
An important reflex to discuss here is the micturition reflex. When the bladder wall is stretched, this information is conveyed back to S234, triggering reflex contraction of the detrusor muscle. When this happens, we feel the urge to pee. However, we can override this reflex through various centres in our brain and through contracting the external urethral sphincter.
Discuss the anatomical reasoning behind differences in referred pain from upper and lower urinary tract infections.
As mentioned, different parts of the urinary tract convey sensory fibres to different parts of the spinal cord. In the kidney, sensory fibres go back to T10/T11, in the ureter they go back to T12/L1, and in the bladder the fibres detecting pain (not stretch) go back to T12/L1. When we feel pain in the urinary tract, we tend to feel it over the dermatomes associated with those sensory nerves: e.g. pain in the kidney is felt over the T10/T11 dermatomes. (However, to my understanding, bladder stones might be felt lower down, like in the S1/S2 dermatomes.)
Describe the anatomy of the urethra; explain the anatomy of its different parts in males and females in relation to continence and catheterisation.
The male urethra is quite long and is divided into three parts (prostatic, intermediate / membranous, and spongy), whereas the female urethra is relatively short and isn't divided into parts. (Some textbooks may consider the pre-prostatic, or intramural, part of the urethra to be a fourth part of the urethra.) Because the female urethra is much shorter, it is easier to catheterise than the male urethra. However, the female urethra is more prone to urinary tract infections than the male urethra. Furthermore, women are more prone to incontinence (though this is also partly because they do crazy stuff like give birth).
An important structure within the male urethra is the verumontanum, also known as the seminal colliculus. The verumontanum is a thickening within the prostatic urethra. It has three orifices: one called the prostatic utricle, and two for the openings of the ejaculatory ducts. The verumontanum is an important marker to look for when removing the prostate via the urethra.
Describe the skeletal and ligamentous components of the pelvis.
Discuss the sexual differences in pelvic skeletal anatomy.
Describe the anatomy and functional importance of the pelvic diaphragm.
Describe the topographical arrangement of anatomical structures within the pelvis.
The pelvis wasn't exactly covered in any of the lectures that we just had (despite pelvic stuff being in the learning outcomes), so I guess it's 2nd year undergrad me to the rescue!
Describe the position and functional anatomy of the kidneys and ureters.
The kidneys are located in the abdomen, roughly between T12 and L3. The right kidney is slightly lower than the left kidney because it has been pushed down by the liver. The hilum of each kidney (where the blood vessels etc. join the kidney) is located at around L1-L2. Each kidney is surrounded by a layer of perirenal (or perinephric) fat, which is surrounded by a layer of renal fascia (a.k.a. Gerota's fascia), and then by a layer of pararenal (paranephric) fat.
Demonstrate the topographical relationships of the kidneys and ureters to other abdominal structures.
The kidneys are located laterally to the psoas muscle, and the ureters run along the front of the psoas. As the ureters enter the pelvis, they cross the bifurcation of the iliac arteries.
Describe the blood supply and innervation of the kidneys and ureters.
Blood supply
The kidneys receive blood from the renal arteries. Since both renal arteries arise from the aorta, and the aorta is on the left side of the body, the left renal artery is shorter than the right renal artery. The opposite is true for renal veins: the left renal vein is longer than the right renal vein. The left renal vein also receives blood from the gonads and adrenals (via the left gonadal vein and the left suprarenal vein respectively).
The ureters receive their blood supply from whatever structures are running close to them. The upper part of the ureters tend to receive blood from the renal artery, the middle part of the ureters tend to receive blood from the gonadal arteries and/or the aorta, and the lower part of the ureters tend to receive blood from the vesical arteries.
Innervation
The kidneys receive sympathetic innervation from T10 and T11 nerves (a.k.a. the lesser splanchnic nerves) and parasympathetic innervation from the vagus nerve. Sensory fibres follow the sympathetic fibres back to T10/T11, so kidney pain tends to be felt over those dermatomes. One important point is that nerves are not very important for renal function in general, but for renal blood flow. Aspects of renal function (how much salt and water to absorb, for example) tend to be controlled by hormones.
The ureters receive sympathetic innervation from T12 and L1, and parasympathetic innervation from the vagus and hypogastric (from S234) nerves. Just like with the kidneys, the sensory fibres follow the sympathetic fibres, so pain in the ureters is felt over T12 and L1.
Describe histology (microscopic anatomy) of the renal cortex and medulla including the renal corpuscle, proximal convoluted tubule, Loop of Henle, distal convoluted tubules, and juxtaglomerular apparatus and collecting tubules.
The outer region of the kidney is called the cortex, and is where the renal corpuscles and convoluted tubules are located. (Don't worry, I'll describe what they are and what they do in a bit.) The area deep to the cortex is the medulla, and contains the Loops of Henle and collecting tubules. There is, however, a bit of overlap between these two areas: the columns of the renal medulla contain the structures of the renal cortex, and the medullary rays of the cortex contain structures of the renal medulla.
Renal corpuscle
The renal corpuscle is made out of the glomerulus (a "knot" made out of arteries) and Bowman's space (the first part of the tubular system where urine is formed). Under the microscope, renal corpuscles basically look like a cluster of cells surrounded by a white ring (the Bowman's capsule). The renal corpuscle is the main site where filtration occurs (i.e. the blood gets filtered so that pretty much everything, except for large proteins, is pushed into the Bowman's capsule and the tubular system).
Proximal convoluted tubule
The proximal convoluted tubule is the first lot of tubules. The reabsorption of pretty much all glucose and amino acids occurs here, along with reabsorption of many other substances. Proximal convoluted cells are tall, columnar, and have a brush border to increase their surface area for reabsorption. Since the Na+/K+ pump is critically important for maintaining concentration gradients for reabsorption, proximal convoluted tubule cells have plenty of mitochondria to keep them topped up and ready to go.
Loop of Henle
The loops of Henle have two parts: a thin descending limb and a thick descending limb. The thin descending limb is more permeable to water than salt, whereas the ascending limb is impermeable to water but permeable to salt. The appearance of the Loops of Henle depends on whether you have a cross-section or a longitudinal section of the loop: cross-sections look like little circles, whereas the longitudinal sections look like long white stripes that are lined by cells. (I think. Histology isn't my strong point.)
Distal convoluted tubules and collecting duct
The distal convoluted tubule and collecting duct cells are similar to those of the proximal convoluted tubule, except that cells in the distal convoluted tubule and collecting duct tend to be cuboidal and less metabolically active than those in the proximal convoluted tubule. Both the distal convoluted tubule and the collecting duct are under hormonal control to change the amount of salts and/or water reabsorbed.
Another point of interest is the juxtaglomerular apparatus. The juxtaglomerular apparatus of the distal tubule interacts with the afferent arteriole by secreting hormones etc. to maintain filtration rate (see here).
Describe the histology of the ureter.
Ureters, like many other bodily tubes, have a mucosa, muscularis layers, and an adventitia. (However, unlike many other bodily tubes, they likely do not have a submucosa.) There are two muscularis layers: one is circular, and one is longitudinal. Together, the muscularis layers work to propel urine towards the bladder.
Describe the anatomy of the urinary bladder, its base and ureteric openings and its relationship to the overlying peritoneum.
The bladder is shaped kind of like an upside-down triangular pyramid. The urethra connects to the bladder at the inferior "point." The umbilical ligament, which is a remnant of an embryonic structure called the urachus, joins at the apex, which is the anterior superior "point." The ureters join at the posterolateral points and continue to pass through the wall of the bladder.
One point of interest is the bladder trigone, which is formed from the intermediate mesoderm of the urogenital septum. This is in contrast to the rest of the bladder, which is formed from the anterior part of an embryonic structure called the cloaca. The bladder trigone makes up part of the posterior wall of the bladder. The ureters open into the bladder at the upper lateral corners of the bladder trigone.
Describe the blood supply and innervation of the urinary bladder.
The bladder receives its blood supply from the superior and inferior vesical arteries. The superior vesical artery comes from the patent part of the umbilical artery, which in turn comes from the anterior division of the internal iliac artery. The inferior vesical artery comes directly from the internal iliac artery.
Like the ureters, the bladder receives sympathetic stimulation from T12 and L1. However, its parasympathetic innervation is only from the hypogastric plexus (S234). Both sympathetic and parasympathetic nerves activate muscles, but they activate different muscles: sympathetic stimulation causes the external urethral sphincter to tighten (and stop you from peeing), while parasympathetic stimulation causes the detrusor muscle (i.e. the bladder muscle) to contract, thus making you pee. Sensory information is a bit mixed: pain fibres follow the sympathetic nerves back to T12 and L1, whereas stretch fibres follow the parasympathetic nerves back to S234.
An important reflex to discuss here is the micturition reflex. When the bladder wall is stretched, this information is conveyed back to S234, triggering reflex contraction of the detrusor muscle. When this happens, we feel the urge to pee. However, we can override this reflex through various centres in our brain and through contracting the external urethral sphincter.
Discuss the anatomical reasoning behind differences in referred pain from upper and lower urinary tract infections.
As mentioned, different parts of the urinary tract convey sensory fibres to different parts of the spinal cord. In the kidney, sensory fibres go back to T10/T11, in the ureter they go back to T12/L1, and in the bladder the fibres detecting pain (not stretch) go back to T12/L1. When we feel pain in the urinary tract, we tend to feel it over the dermatomes associated with those sensory nerves: e.g. pain in the kidney is felt over the T10/T11 dermatomes. (However, to my understanding, bladder stones might be felt lower down, like in the S1/S2 dermatomes.)
Describe the anatomy of the urethra; explain the anatomy of its different parts in males and females in relation to continence and catheterisation.
The male urethra is quite long and is divided into three parts (prostatic, intermediate / membranous, and spongy), whereas the female urethra is relatively short and isn't divided into parts. (Some textbooks may consider the pre-prostatic, or intramural, part of the urethra to be a fourth part of the urethra.) Because the female urethra is much shorter, it is easier to catheterise than the male urethra. However, the female urethra is more prone to urinary tract infections than the male urethra. Furthermore, women are more prone to incontinence (though this is also partly because they do crazy stuff like give birth).
An important structure within the male urethra is the verumontanum, also known as the seminal colliculus. The verumontanum is a thickening within the prostatic urethra. It has three orifices: one called the prostatic utricle, and two for the openings of the ejaculatory ducts. The verumontanum is an important marker to look for when removing the prostate via the urethra.
Describe the skeletal and ligamentous components of the pelvis.
Discuss the sexual differences in pelvic skeletal anatomy.
Describe the anatomy and functional importance of the pelvic diaphragm.
Describe the topographical arrangement of anatomical structures within the pelvis.
The pelvis wasn't exactly covered in any of the lectures that we just had (despite pelvic stuff being in the learning outcomes), so I guess it's 2nd year undergrad me to the rescue!
Friday, March 29, 2019
Tumours of the Bladder and Kidneys
List the major types of neoplasms of the kidney
Kidney tumours can be either benign (e.g. renal papillary adenoma) or malignant (e.g. renal cell carcinoma). In this post, I'll only be covering renal cell carcinoma because it was the only one talked about in depth in the lectures (probably because it's by far and away the most common). Clear cell renal cell carcinomas are the most common type of renal cell carcinomas.
Outline the aetiology, risk factors for development and pathogenesis of kidney neoplasms
Risk factors of renal cell carcinoma are pretty much the same as risk factors for many other illnesses: smoking, hypertension, obesity, genetic factors, and exposure to certain toxic chemicals. It is most commonly seen in men aged 50-70.
One genetic cause of renal cell carcinoma is Von Hippel-Lindau disease, which is a genetic disorder in which the VHL tumour suppressor gene on chromosome 3 is mutated. There are also sporadic forms of the disease in which one of the VHL genes has been lost (due to some kind of deletion of the short arm of chromosome 3), and then the other gene becomes mutated. Inactivation of VHL results in an increase in IGF-1, which is a growth factor that can upregulate hypoxia-inducible factors and ultimately vascular endothelial growth factor (VEGF).
List, in brief, the morphological and histological features of kidney neoplasms
Renal cell carcinoma arises from the epithelial cells of the proximal convoluted tubule. The cells look clear under the microscope and yellow macroscopically (i.e. to the naked eye), as the cells are filled with carbohydrates and lipids.
Outline the clinical presentations of kidney neoplasms
Renal cell carcinoma is usually pretty silent and is often simply picked up when patients are scanned for some other reason. Alternatively, patients might not get noticed at all until their disease has become severe. In patients who do show symptoms, the classic signs include haematuria, abdominal mass, and flank pain, though there may also be other symptoms. For instance, if the carcinoma spreads into the inferior vena cava and obstructs the left gonadal vein, it can result in scrotal varices. There may also be paraneoplastic syndromes from inappropriate secretion of hormones: hypercalcaemia from parathyroid hormone-related protein (PTHrP), erythrocytosis from EPO, hypertension from renin, and even Cushing's syndrome from ectopic ACTH.
Renal cell carcinoma is relatively resistant to traditional chemotherapy and radiotherapy, so surgery is often used as treatment. Immunomodulatory and anti-VEGF treatments may also be tried.
Provide an overview of staging of kidney neoplasms
Staging of renal cell carcinoma is generally done using the TNM system. The T stands for "tumour" and refers to a tumour that has not spread beyond the original site. The N stands for "nodes" and refers to a tumour that has spread to lymph nodes. Finally, the M stands for "metastatic" and refers to a tumour that has spread around the body.
List the major types of lower urinary tract neoplastic disease
The main types of bladder tumours are urothelial carcinoma (a.k.a. transitional cell carcinoma) and squamous cell carcinoma. Urothelial carcinoma is by far the most common in Australia, though squamous cell carcinoma is more common in areas where schistosomiasis (a parasite disease) is endemic.
Outline the aetiology, risk factors for development and pathogenesis of lower urinary tract neoplastic disease
List, in brief, the morphological and histological features of lower urinary tract neoplastic disease
Smoking and certain carcinogenic substances are the main risk factors for bladder cancers. They are most commonly seen in older men.
Urothelial carcinoma may have one of two types of precursor lesions: flat or papillary. Flat precursor lesions include urothelial carcinoma in situ, whereas papillary precursor lesions include papillary urothelial carcinoma. The flat precursors are more often seen in p53-dependent tumours, which tend to be more aggressive than p53-independent tumours, which often have papillary precursors. (p53 is a tumour suppressor gene that is important in the development of many cancers.)
Urothelial carcinoma is multifocal (meaning it can affect multiple sites) and recurrent (meaning that it comes back). There are two main theories as to why this is so: field effect theory and implantation theory. The field effect theory states that whatever caused the first cancer might have affected nearby sites, whereas the implantation theory states that cells from the first tumour could have broken off and implanted somewhere else. In reality, it could be a mixture of the two.
Treatment of urothelial carcinoma is basically a mix of surgery, radiation, and/or chemotherapy, depending on the situation.
Outline the clinical presentations of lower urinary tract neoplastic disease
Bladder cancer often presents with painless haematuria. Remember: painless haematuria is malignancy unless proven otherwise.
Provide an overview of staging of lower urinary tract neoplastic disease
Just like renal cell carcinoma, urothelial carcinoma also uses TNM staging. The T stage can be further divided up depending on where the tumour is. At the T1 stage, the tumour is in the lamina propria. T2 means that the tumour is in the muscularis propria, T3 in the perivesical fat, and T4 in adjacent organs. N refers to invasion of nodes, whereas M refers to metastasis.
Kidney tumours can be either benign (e.g. renal papillary adenoma) or malignant (e.g. renal cell carcinoma). In this post, I'll only be covering renal cell carcinoma because it was the only one talked about in depth in the lectures (probably because it's by far and away the most common). Clear cell renal cell carcinomas are the most common type of renal cell carcinomas.
Outline the aetiology, risk factors for development and pathogenesis of kidney neoplasms
Risk factors of renal cell carcinoma are pretty much the same as risk factors for many other illnesses: smoking, hypertension, obesity, genetic factors, and exposure to certain toxic chemicals. It is most commonly seen in men aged 50-70.
One genetic cause of renal cell carcinoma is Von Hippel-Lindau disease, which is a genetic disorder in which the VHL tumour suppressor gene on chromosome 3 is mutated. There are also sporadic forms of the disease in which one of the VHL genes has been lost (due to some kind of deletion of the short arm of chromosome 3), and then the other gene becomes mutated. Inactivation of VHL results in an increase in IGF-1, which is a growth factor that can upregulate hypoxia-inducible factors and ultimately vascular endothelial growth factor (VEGF).
List, in brief, the morphological and histological features of kidney neoplasms
Renal cell carcinoma arises from the epithelial cells of the proximal convoluted tubule. The cells look clear under the microscope and yellow macroscopically (i.e. to the naked eye), as the cells are filled with carbohydrates and lipids.
Outline the clinical presentations of kidney neoplasms
Renal cell carcinoma is usually pretty silent and is often simply picked up when patients are scanned for some other reason. Alternatively, patients might not get noticed at all until their disease has become severe. In patients who do show symptoms, the classic signs include haematuria, abdominal mass, and flank pain, though there may also be other symptoms. For instance, if the carcinoma spreads into the inferior vena cava and obstructs the left gonadal vein, it can result in scrotal varices. There may also be paraneoplastic syndromes from inappropriate secretion of hormones: hypercalcaemia from parathyroid hormone-related protein (PTHrP), erythrocytosis from EPO, hypertension from renin, and even Cushing's syndrome from ectopic ACTH.
Renal cell carcinoma is relatively resistant to traditional chemotherapy and radiotherapy, so surgery is often used as treatment. Immunomodulatory and anti-VEGF treatments may also be tried.
Provide an overview of staging of kidney neoplasms
Staging of renal cell carcinoma is generally done using the TNM system. The T stands for "tumour" and refers to a tumour that has not spread beyond the original site. The N stands for "nodes" and refers to a tumour that has spread to lymph nodes. Finally, the M stands for "metastatic" and refers to a tumour that has spread around the body.
List the major types of lower urinary tract neoplastic disease
The main types of bladder tumours are urothelial carcinoma (a.k.a. transitional cell carcinoma) and squamous cell carcinoma. Urothelial carcinoma is by far the most common in Australia, though squamous cell carcinoma is more common in areas where schistosomiasis (a parasite disease) is endemic.
Outline the aetiology, risk factors for development and pathogenesis of lower urinary tract neoplastic disease
List, in brief, the morphological and histological features of lower urinary tract neoplastic disease
Smoking and certain carcinogenic substances are the main risk factors for bladder cancers. They are most commonly seen in older men.
Urothelial carcinoma may have one of two types of precursor lesions: flat or papillary. Flat precursor lesions include urothelial carcinoma in situ, whereas papillary precursor lesions include papillary urothelial carcinoma. The flat precursors are more often seen in p53-dependent tumours, which tend to be more aggressive than p53-independent tumours, which often have papillary precursors. (p53 is a tumour suppressor gene that is important in the development of many cancers.)
Urothelial carcinoma is multifocal (meaning it can affect multiple sites) and recurrent (meaning that it comes back). There are two main theories as to why this is so: field effect theory and implantation theory. The field effect theory states that whatever caused the first cancer might have affected nearby sites, whereas the implantation theory states that cells from the first tumour could have broken off and implanted somewhere else. In reality, it could be a mixture of the two.
Treatment of urothelial carcinoma is basically a mix of surgery, radiation, and/or chemotherapy, depending on the situation.
Outline the clinical presentations of lower urinary tract neoplastic disease
Bladder cancer often presents with painless haematuria. Remember: painless haematuria is malignancy unless proven otherwise.
Provide an overview of staging of lower urinary tract neoplastic disease
Just like renal cell carcinoma, urothelial carcinoma also uses TNM staging. The T stage can be further divided up depending on where the tumour is. At the T1 stage, the tumour is in the lamina propria. T2 means that the tumour is in the muscularis propria, T3 in the perivesical fat, and T4 in adjacent organs. N refers to invasion of nodes, whereas M refers to metastasis.
Sunday, March 24, 2019
Urinary tract congnital anomalies, cystic disease, urolithiasis, and obstructive disease
List the major types of congenital malformations affecting the
kidney
Describe the anatomical and renal functional defects of the major types of congenital malformations affecting the kidney
The major types of congenital malformations affecting the kidney are agenesis of the kidney, kidney hypoplasia, ectopic kidneys, and horseshoe kidneys.
Agenesis
Agenesis involves the absence of one or both kidneys. Bilateral renal agenesis, also known as Potter's syndrome, is incompatible with life, as not only does it result in oligohydramnios (decreased urine output), it also results in hypoplastic lungs (small lungs that haven't formed properly). Fetuses with Potter's disease tend to have very "squashed" faces. Unilateral agenesis, on the other hand, is usually asymptomatic, partly because the remaining kidney may undergo compensatory hypertrophy. Patients with unilateral renal agenesis may also be other abnormalities of the genitourinary tract.
Hypoplasia
Hypoplastic kidneys have developed normally, but are small. Usually only one kidney is affected.
Ectopic kidneys
Ectopic kidneys are kidneys that aren't where they're supposed to be (between around T12 and L3). Usually ectopic kidneys are found in the pelvis due to failure to ascend, but rarely you might get a kidney that has managed to ascend all the way into the thorax. Most ectopic kidneys are either normal sized or slightly smaller.
Horseshoe kidneys
Horseshoe kidneys are formed from fusion of the upper or lower poles of the kidneys. They are usually located quite low down as their ascension is obstructed by the inferior mesenteric artery. Usually horseshoe kidneys have numerous renal arteries supplying them.
Outline the major types of cystic disease of the kidney in terms of aetiology, pathogenesis, clinical features and complications
Cystic diseases are, well, diseases in which there are cysts. There are a range of cystic kidney diseases, but in this post we will only focus on some of the main ones.
Simple renal cysts
Simple, or localised, renal cysts are incredibly common, especially in patients over the age of 50. However, simple cysts are usually asymptomatic. There is a risk of rupture, causing haematuria, pain, and so on, but usually the biggest problem with simple renal cysts is that a malignant tumour might be mistaken as a simple renal cyst. There are some clues, however, that might help in differentiating a malignancy from a simple cyst: multiple septa, thickened cyst walls, and solid areas within or around cysts are all clues to malignancy.
Cystic renal dysplasia
Cystic renal dysplasia is malformation of the kidney (or kidneys- it can be either unilateral or bilateral) with cysts of various sizes. It is a common cause of abdominal mass in infants. Under the microscope, kidneys look abnormal and have many immature structures.
Polycystic kidney disease
Polycystic kidney disease is characterised by fluid-filled cysts in the kidney. It comes in two flavours: autosomal dominant (ADPKD) and autosomal recessive (ARPKD).
ADPKD is the most common type of polycystic kidney disease. The three main genes identified are PKD-1, PKD-2, and PKD-3. Cyst formation begins in utero but progresses very slowly, so patients usually don't present until they are in their 30s or even in their 50s. Due to the formation of cysts, the kidneys can become quite large and the cysts can compress surrounding renal tissue. The resulting damage can cause symptoms such as pain and haematuria.
ARPKD is rare and involves the PKHD1 gene. The kidneys appear smooth and have small cysts. ARPKD, unlike ADPKD, presents quite early on (in childhood or even in infancy).
Classify the different forms of urinary tract obstruction according to aetiology, pathogenesis, morphology, clinical features and complications.
Explain how urinary tract obstruction can lead to kidney injury
Obstructive uropathy is a fancy term that refers to obstruction anywhere in the urinary tract. There are many causes of obstructive uropathy, but they tend to lead to dilation of the renal pelvis and calyces and eventual enlargement of the kidney. The bladder may also have a thick wall. Hydronephrosis may occur as a result of obstructive uropathy. In hydronephrosis, the urine backs up, causing distension and dilation of the renal pelvis and calyces. Eventually, this can lead to atrophy of the kidney, because while kidneys can dish out urine like it's nobody's business, they can't take it.
Urolithiasis, or kidney stones, is a common cause of obstructive uropathy. There are many types of kidney stones, all formed by various solutes precipitating out of solution. Dehydration, hypercalciuria, and several other conditions can all conspire to increase the risk of kidney stones. Certain bacteria (Proteus and Klebsiella) may even be responsible for stones that are made out of struvite (magnesium ammonium phosphate). Such stones are quite large and are sometimes known as "staghorn calculi" because they are shaped somewhat like the horns of a stag.
Kidney stones might be painless if they are small, but if they are larger, they can cause pain and other symptoms related to obstructive uropathy. If they cause damage, they may also result in haematuria and/or infection. If the kidney stones are large, one type of pain that might be experienced is "renal colic," which is an excruciating pain that radiates from the flank to the groin. Renal colic might also be accompanied with other symptoms, from haematuria to vomiting. I have discussed treatment of kidney stones here.
Describe the anatomical and renal functional defects of the major types of congenital malformations affecting the kidney
The major types of congenital malformations affecting the kidney are agenesis of the kidney, kidney hypoplasia, ectopic kidneys, and horseshoe kidneys.
Agenesis
Agenesis involves the absence of one or both kidneys. Bilateral renal agenesis, also known as Potter's syndrome, is incompatible with life, as not only does it result in oligohydramnios (decreased urine output), it also results in hypoplastic lungs (small lungs that haven't formed properly). Fetuses with Potter's disease tend to have very "squashed" faces. Unilateral agenesis, on the other hand, is usually asymptomatic, partly because the remaining kidney may undergo compensatory hypertrophy. Patients with unilateral renal agenesis may also be other abnormalities of the genitourinary tract.
Hypoplasia
Hypoplastic kidneys have developed normally, but are small. Usually only one kidney is affected.
Ectopic kidneys
Ectopic kidneys are kidneys that aren't where they're supposed to be (between around T12 and L3). Usually ectopic kidneys are found in the pelvis due to failure to ascend, but rarely you might get a kidney that has managed to ascend all the way into the thorax. Most ectopic kidneys are either normal sized or slightly smaller.
Horseshoe kidneys
Horseshoe kidneys are formed from fusion of the upper or lower poles of the kidneys. They are usually located quite low down as their ascension is obstructed by the inferior mesenteric artery. Usually horseshoe kidneys have numerous renal arteries supplying them.
Outline the major types of cystic disease of the kidney in terms of aetiology, pathogenesis, clinical features and complications
Cystic diseases are, well, diseases in which there are cysts. There are a range of cystic kidney diseases, but in this post we will only focus on some of the main ones.
Simple renal cysts
Simple, or localised, renal cysts are incredibly common, especially in patients over the age of 50. However, simple cysts are usually asymptomatic. There is a risk of rupture, causing haematuria, pain, and so on, but usually the biggest problem with simple renal cysts is that a malignant tumour might be mistaken as a simple renal cyst. There are some clues, however, that might help in differentiating a malignancy from a simple cyst: multiple septa, thickened cyst walls, and solid areas within or around cysts are all clues to malignancy.
Cystic renal dysplasia
Cystic renal dysplasia is malformation of the kidney (or kidneys- it can be either unilateral or bilateral) with cysts of various sizes. It is a common cause of abdominal mass in infants. Under the microscope, kidneys look abnormal and have many immature structures.
Polycystic kidney disease
Polycystic kidney disease is characterised by fluid-filled cysts in the kidney. It comes in two flavours: autosomal dominant (ADPKD) and autosomal recessive (ARPKD).
ADPKD is the most common type of polycystic kidney disease. The three main genes identified are PKD-1, PKD-2, and PKD-3. Cyst formation begins in utero but progresses very slowly, so patients usually don't present until they are in their 30s or even in their 50s. Due to the formation of cysts, the kidneys can become quite large and the cysts can compress surrounding renal tissue. The resulting damage can cause symptoms such as pain and haematuria.
ARPKD is rare and involves the PKHD1 gene. The kidneys appear smooth and have small cysts. ARPKD, unlike ADPKD, presents quite early on (in childhood or even in infancy).
Classify the different forms of urinary tract obstruction according to aetiology, pathogenesis, morphology, clinical features and complications.
Explain how urinary tract obstruction can lead to kidney injury
Obstructive uropathy is a fancy term that refers to obstruction anywhere in the urinary tract. There are many causes of obstructive uropathy, but they tend to lead to dilation of the renal pelvis and calyces and eventual enlargement of the kidney. The bladder may also have a thick wall. Hydronephrosis may occur as a result of obstructive uropathy. In hydronephrosis, the urine backs up, causing distension and dilation of the renal pelvis and calyces. Eventually, this can lead to atrophy of the kidney, because while kidneys can dish out urine like it's nobody's business, they can't take it.
Urolithiasis, or kidney stones, is a common cause of obstructive uropathy. There are many types of kidney stones, all formed by various solutes precipitating out of solution. Dehydration, hypercalciuria, and several other conditions can all conspire to increase the risk of kidney stones. Certain bacteria (Proteus and Klebsiella) may even be responsible for stones that are made out of struvite (magnesium ammonium phosphate). Such stones are quite large and are sometimes known as "staghorn calculi" because they are shaped somewhat like the horns of a stag.
Kidney stones might be painless if they are small, but if they are larger, they can cause pain and other symptoms related to obstructive uropathy. If they cause damage, they may also result in haematuria and/or infection. If the kidney stones are large, one type of pain that might be experienced is "renal colic," which is an excruciating pain that radiates from the flank to the groin. Renal colic might also be accompanied with other symptoms, from haematuria to vomiting. I have discussed treatment of kidney stones here.
Vascular and Tubulointerstitial Diseases of the Kidney
This lecture actually did have some more learning outcomes, but I think I might actually just stick to using the diseases as headings.
Vascular Diseases
Vascular diseases of the kidney, as the name implies, are diseases that affect the vasculature of the kidney.
Hypertensive nephrosclerosis
Hypertensive nephrosclerosis is scarring (sclerosis) of the kidney (nephro-) due to hypertension. Hypertensive nephrosclerosis can be either benign or malignant. Benign nephrosclerosis is due to chronic hypertension, defined as a blood pressure greater than 140/90, whereas malignant nephrosclerosis is due to accelerated hypertension (i.e. a rapid spike in blood pressure) or malignant hypertension, defined as a blood pressure greater than 180/110 with acute end-organ damage.
Benign hypertensive nephrosclerosis is the third most common cause of chronic renal failure. Over time, the small arteries and arterioles become thickened and there is damage to the glomeruli and tubules. Benign hypertensive nephrosclerosis may be asymptomatic with proteinuria, but over time it may progress to chronic renal failure. Malignant hypertensive nephrosclerosis is a medical emergency in which the damage is quite severe, and may present as acute renal failure. Under the microscope, there is fibrinoid necrosis of arterioles and hyperplastic arteriolosclerosis.
Renal artery stenosis
Renal artery stenosis is narrowing (stenosis) of the renal artery, which can lead to secondary hypertension. (As you can see, there can be a bit of interplay between the kidneys and hypertension: renal artery stenosis can lead to hypertension, which can lead to hypertensive nephrosclerosis.) Renal artery stenosis is usually due to atherosclerosis in elderly patients, but it can also be due to fibromuscular dysplasia in young women. (Fibromuscular dysplasia involves segmental thickening of arteries, which looks kind of like a string of beads on angiography. So far, the cause of this is unknown.)
One of the problems with renal artery stenosis is that it decreases blood flow to the kidneys, activating the RAAS, which increases vasoconstriction. The vasoconstriction triggered by the RAAS exacerbates the problem, forming a vicious cycle.
Tubulointerstitial Diseases
Tubulointerstitial diseases are diseases that affect the tubules and the interstitium of the kidney. (I love it when names are logical!)
Acute tubular necrosis
Acute tubular necrosis is one of the most common causes of renal failure. Acute tubular necrosis is necrosis of the kidney tubules (again, I'm loving these logical names), which may be due to ischaemia or toxins. There are three main phases of acute tubular necrosis: initiation, maintenance, and recovery. In the initiation phase, there is mild oliguria and a mild increase in serum creatinine. In the maintenance phase, oliguria and the increase in serum creatinine continue. There may also be uraemia. Finally, in the recovery phase, there is a large amount of diuresis (peeing). Because you're losing a lot of fluid pretty rapidly, you're also losing a lot of electrolytes at the same time, which can pose other problems.
Tubulointerstitial nephritis
Tubulointerstitial nephritis is inflammation of the tubules of the kidney. Tubulointerstitial nephritis may be either acute or chronic, with the chronic form being irreversible. There are many causes of tubulointerstitial nephritis but the main one to be aware of is drugs, particularly NSAIDs, proton pump inhibitors, and antibiotics. Unfortunately, drug-related tubulointerstitial nephritis is somewhat hard to predict: we don't really know who will get it and at what dose. It is thought that drugs act as a hapten in order to trigger an immune response (see here for information on what a hapten is).
It is important to distinguish between acute tubulointerstitial nephritis and acute pyelonephritis, as the two conditions may present similarly. (Apparently we will be learning about acute pyelonephritis next week, so stay tuned!) While acute tubulointerstitial nephritis is often drug-related and can be treated by simply removing the drug (and perhaps also giving some steroids), acute pyelonephritis is usually due to an ascending UTI that can be treated with antibiotics.
Chronic pyelonephritis
Chronic pyelonephritis is chronic inflammation of the kidney. It is usually due to either reflex nephropathy (reflux of urine back into the kidney) or obstructive nephropathy (some obstruction to urinary outflow). The kidney surface can have very deep, irregular scars, and under the microscope the inflammation can be so severe that the tubules look almost like the follicles of the thyroid gland. (This is also known as "tubular thyroidisation.")
Myeloma kidney
Myeloma kidney is a result of plasma cell myeloma (a.k.a. multiple myeloma). As the name suggests, plasma cell myeloma is a malignant proliferation of plasma cells (i.e. antibody-producing B cells). Plasma cell myelomas secrete large amounts of the same antibody, and sometimes these antibodies might be abnormal. For instance, the antibodies that are secreted might only consist of light chains. There are a range of complications that can result from myeloma kidney, but for now we'll only focus on two: myeloma cast nephropathy and amyloidosis.
Myeloma cast nephropathy occurs when abnormal light chains precipitate out of solution, forming casts. These casts can clog up the tubules, resulting in acute renal failure. Under immunofluorescence, these light chains will consist of only kappa chains or only lambda light chains (remember, in myeloma, large amounts of the same antibody are being made).
Amyloidosis is characterised by a build-up of amyloid, which consists of abnormally-folded extracellular proteins that resist degradation. Amyloid can be visualised with the Congo red stain. Under the Congo red stain, they stain salmon-pink, and if seen under polarised light while stained, they appear apple-green. In myeloma kidney, amyloidosis occurs due to the light chains in myeloma, and thus this type of amyloid is called AL-amyloid. Amyloid can deposit in a range of places in the kidney, causing a lot of problems.
Vascular Diseases
Vascular diseases of the kidney, as the name implies, are diseases that affect the vasculature of the kidney.
Hypertensive nephrosclerosis
Hypertensive nephrosclerosis is scarring (sclerosis) of the kidney (nephro-) due to hypertension. Hypertensive nephrosclerosis can be either benign or malignant. Benign nephrosclerosis is due to chronic hypertension, defined as a blood pressure greater than 140/90, whereas malignant nephrosclerosis is due to accelerated hypertension (i.e. a rapid spike in blood pressure) or malignant hypertension, defined as a blood pressure greater than 180/110 with acute end-organ damage.
Benign hypertensive nephrosclerosis is the third most common cause of chronic renal failure. Over time, the small arteries and arterioles become thickened and there is damage to the glomeruli and tubules. Benign hypertensive nephrosclerosis may be asymptomatic with proteinuria, but over time it may progress to chronic renal failure. Malignant hypertensive nephrosclerosis is a medical emergency in which the damage is quite severe, and may present as acute renal failure. Under the microscope, there is fibrinoid necrosis of arterioles and hyperplastic arteriolosclerosis.
Renal artery stenosis
Renal artery stenosis is narrowing (stenosis) of the renal artery, which can lead to secondary hypertension. (As you can see, there can be a bit of interplay between the kidneys and hypertension: renal artery stenosis can lead to hypertension, which can lead to hypertensive nephrosclerosis.) Renal artery stenosis is usually due to atherosclerosis in elderly patients, but it can also be due to fibromuscular dysplasia in young women. (Fibromuscular dysplasia involves segmental thickening of arteries, which looks kind of like a string of beads on angiography. So far, the cause of this is unknown.)
One of the problems with renal artery stenosis is that it decreases blood flow to the kidneys, activating the RAAS, which increases vasoconstriction. The vasoconstriction triggered by the RAAS exacerbates the problem, forming a vicious cycle.
Tubulointerstitial Diseases
Tubulointerstitial diseases are diseases that affect the tubules and the interstitium of the kidney. (I love it when names are logical!)
Acute tubular necrosis
Acute tubular necrosis is one of the most common causes of renal failure. Acute tubular necrosis is necrosis of the kidney tubules (again, I'm loving these logical names), which may be due to ischaemia or toxins. There are three main phases of acute tubular necrosis: initiation, maintenance, and recovery. In the initiation phase, there is mild oliguria and a mild increase in serum creatinine. In the maintenance phase, oliguria and the increase in serum creatinine continue. There may also be uraemia. Finally, in the recovery phase, there is a large amount of diuresis (peeing). Because you're losing a lot of fluid pretty rapidly, you're also losing a lot of electrolytes at the same time, which can pose other problems.
Tubulointerstitial nephritis
Tubulointerstitial nephritis is inflammation of the tubules of the kidney. Tubulointerstitial nephritis may be either acute or chronic, with the chronic form being irreversible. There are many causes of tubulointerstitial nephritis but the main one to be aware of is drugs, particularly NSAIDs, proton pump inhibitors, and antibiotics. Unfortunately, drug-related tubulointerstitial nephritis is somewhat hard to predict: we don't really know who will get it and at what dose. It is thought that drugs act as a hapten in order to trigger an immune response (see here for information on what a hapten is).
It is important to distinguish between acute tubulointerstitial nephritis and acute pyelonephritis, as the two conditions may present similarly. (Apparently we will be learning about acute pyelonephritis next week, so stay tuned!) While acute tubulointerstitial nephritis is often drug-related and can be treated by simply removing the drug (and perhaps also giving some steroids), acute pyelonephritis is usually due to an ascending UTI that can be treated with antibiotics.
Chronic pyelonephritis
Chronic pyelonephritis is chronic inflammation of the kidney. It is usually due to either reflex nephropathy (reflux of urine back into the kidney) or obstructive nephropathy (some obstruction to urinary outflow). The kidney surface can have very deep, irregular scars, and under the microscope the inflammation can be so severe that the tubules look almost like the follicles of the thyroid gland. (This is also known as "tubular thyroidisation.")
Myeloma kidney
Myeloma kidney is a result of plasma cell myeloma (a.k.a. multiple myeloma). As the name suggests, plasma cell myeloma is a malignant proliferation of plasma cells (i.e. antibody-producing B cells). Plasma cell myelomas secrete large amounts of the same antibody, and sometimes these antibodies might be abnormal. For instance, the antibodies that are secreted might only consist of light chains. There are a range of complications that can result from myeloma kidney, but for now we'll only focus on two: myeloma cast nephropathy and amyloidosis.
Myeloma cast nephropathy occurs when abnormal light chains precipitate out of solution, forming casts. These casts can clog up the tubules, resulting in acute renal failure. Under immunofluorescence, these light chains will consist of only kappa chains or only lambda light chains (remember, in myeloma, large amounts of the same antibody are being made).
Amyloidosis is characterised by a build-up of amyloid, which consists of abnormally-folded extracellular proteins that resist degradation. Amyloid can be visualised with the Congo red stain. Under the Congo red stain, they stain salmon-pink, and if seen under polarised light while stained, they appear apple-green. In myeloma kidney, amyloidosis occurs due to the light chains in myeloma, and thus this type of amyloid is called AL-amyloid. Amyloid can deposit in a range of places in the kidney, causing a lot of problems.
Glomerulonephritis
Yes, I'm skipping ahead to another pathology lecture. Yes, I know that I've written more about pathology than about any other field this year. Unfortunately, pathology is the area that I've been struggling with the most, so it's the area I'm writing about the most, and unless anyone comments asking for me to cover a different topic, I'm just going to keep ploughing ahead.
This lecture was long, but it only had one learning outcome: "Classify glomerulonephritis with reference to aetiology, pathogenesis, clinical presentation, key morphological findings and natural history." I will be using my own headings for this post instead.
Clinical Presentations of Renal Disease
There are four (or five, depending on how you count them) main presentations of renal disease: acute renal failure, chronic renal failure, nephritic syndrome, and nephrotic syndrome. There is also rapidly-progressing glomerulonephritis, which is a subset of nephritic syndrome. Renal diseases are very common: around 40% of adults over 75 will have indicators of chronic kidney disease, and this number is even higher in Indigenous populations.
Acute renal failure
Acute renal failure is characterised by azotaemia, which is a rapid rise in serum urea and/or creatinine (a marker of renal function). There may also be uraemia, which is essentially just symptomatic azotaemia (symptoms include lethargy, decreased appetite, shortness of breath, peripheral neuropathy, and oedema). Other symptoms include oliguria (reduced urine output), or maybe even anuria (no urine output). Symptoms arise over days to weeks and may completely resolve (though there is a chance of progressing to chronic renal failure).
Causes of renal failure can be classified into three categories: pre-renal, renal, and post-renal. Pre-renal causes encompass basically anything that affects the blood supply to the kidneys. Renal failure encompasses intrinsic kidney diseases, and post-renal causes encompass anything that affects urine outflow.
Chronic renal failure
Chronic renal failure is basically the same as acute renal failure, but it is over a longer period of time (months to years). Furthermore, chronic renal failure is irreversible and will eventually progress to end-stage renal failure, defined as a glomerular filtration rate of less than 5% of normal. Treatment of chronic renal failure aims to delay progression.
Nephritic syndrome
Nephritic syndrome is a set of symptoms that includes azotaemia/uraemia, oliguria, macroscopic haematuria (blood in the urine that you can see), mild/moderate proteinuria, and hypertension. It is usually caused by glomerulonephritis (disease that affects the glomerulus). Rapidly-progressive glomerulonephritis (RPGN) is a subset of nephritic syndrome in which the rise in serum urea and creatinine is very rapid. RPGN is usually due to a subset of glomerulonephritis called crescentic glomerulonephritis.
Nephrotic syndrome
Nephrotic syndrome is a set of symptoms that includes proteinuria (>3.5g/24h), hypoalbuminaemia, peripheral oedema, hyperlipidaemia, and lipiduria. Nephrotic syndrome, like nephritic syndrome, is usually due to glomerulonephritis. If glomerulonephritis increases the permeability of glomerular capillaries, proteins can leak out into the urine, resulting in proteinuria. Since protein is leaving the body through the urine, there is low protein in the serum, leading to hypoalbuminaemia and a reduced serum oncotic pressure, which in turn can lead to peripheral oedema. At the same time, there is increased hepatic lipid synthesis, leading to hyperlipidaemia and eventually lipiduria.
Glomerulonephritis
I've mentioned glomerulonephritis before, but what is it exactly? Well, glomerulonephritis refers to a range of diseases that affect the glomeruli of the kidneys. Most of these diseases are mediated by the formation of immune complexes or structural issues. Diagnostic tools for glomerulonephritis include light microscopy, immunofluorescence, and electron microscopy. Glomerulonephritis can be iether primary or secondary: primary glomerulonephritis has no identifiable cause, whereas secondary glomerulonephritis is due to a recognisable cause (e.g. drugs, infections, etc.).
Glomerulonephritis can present in different ways, depending on the specific disease. Some types of glomerulonephritis have a presentation resembling nephrotic syndrome, whereas others have a presentation resembling nephritic syndrome. In this post, I'll be starting with the most "nephrotic" types of glomerulonephritis and working my way towards the most "nephritic" types of glomerulonephritis.
Minimal change disease
Minimal change disease is a type of glomerulonephritis that mainly affects children and presents with nephrotic syndrome. It is a disease mediated by structural changes, in particular of the podocytes surrounding glomerular capillaries. As you can guess by the name, there are minimal changes in the diagnostic tests. Light microscopy and immunofluorescence both look normal: you have to use electron microscopy to see the difference. Normal podocytes have "slit diaphragms" between the foot processes, and these "slit diaphragms" have the negative charge that repels proteins and stops them from getting into the urine. In minimal change disease, foot processes are effaced and fused together, meaning that the slit diaphragms and the repulsive negative charge are lost, allowing proteins to leak into the urine, resulting in nephrotic syndrome.
Prognosis of minimal change disease is very good in children, as it responds well to steroids in this population. The response in adults, however, is less predictable.
Membranous nephropathy
Membranous nephropathy mainly affects adults and results in nephrotic syndrome. It is mediated by immune complexes that deposit in the subepithelial space (i.e. under the podocytes but outside the basement membrane... I think). Basement membrane "spikes" (thickening of the basement membrane) appear between the deposits of immune complexes. Immunofluorescence shows granular IgG and C3.
Unlike with other forms of glomerulonephritis, primary membranous nephropathy now has an identifiable cause. Primary membranous nephropathy is due to autoantibodies to the podocyte phospholipase A2 receptor. Secondary membranous nephropathy can be all the usual suspects: drugs, infections, autoimmune diseases, etc.
Prognosis of membranous nephropathy is quite variable. 40% of patients will go into pontaneous remission. However, 40% of patients will progress to chronic renal failure. The remaining 20% of patients will have stable disease.
Focal segmental glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis (FSGS) is focal, meaning that less than 50% of all glomeruli are affected, and segmental, meaning that less than 50% of an individual glomerulus is affected. (Just for comparison: diffuse means that more than 50% of all glomeruli are affected, whereas global means that more than 50% of individual glomeruli are affected). FSGS is the most common cause of nephrotic syndrome in adults and is due to structural abnormalities in the podocytes.
As the "sclerosis" part of the name suggests, there is scarring involved in FSGS. Scarring can be seen under both light and electron microscopy. FSGS is not immune-mediated, but due to scarring, larger antibodies such as IgM may be trapped and can be identified under immunofluorescence. Sometimes, complement molecules such as C3 may be also be activated by the trapping of IgM.
Prognosis of FSGS is not the worst, but it's not the best either. Around 30% of patients respond to steroids, but the rest progress to chronic renal failure.
IgA nephropathy (a.k.a. Berger's disease)
IgA nephropathy is the most common cause of glomerulonephritis worldwide and usually affects young adults. It is immune-complex mediated and presents with nephritic syndrome (note: this is the first type of glomerulonephritis I've spoken about so far that presents with nephritic, rather than nephrotic, syndrome). Under light microscopy, there is mesangial matrix expansion and hypercellularity, and under electron microscopy, the immune-complexes can be seen. Immunofluorescence reveals granular IgA (hence why this disease is called IgA nephropathy).
Prognosis of IgA nephropathy follows the "Rule of Thirds": around 1/3 resolve spontaneously, 1/3 have stable disease, and 1/3 progress to FSGS and/or chronic renal failure.
Post-infectious glomerulonephritis (a.k.a. acute proliferative glomerulonephritis or post-streptococcal glomerulonephritis)
Post-infectious glomerulonephritis usually affects children around 1-4 weeks after a bout of cellulitis or pharyngitis. It is immune-complex mediated and is often a response to streptococcal pyrogenic exotoxin B, which is why this disease is sometimes called post-streptococcal glomerulonephritis. (Note, however, that Streptococcus species are not the only species that can cause this disease.) Post-infectious glomerulonephritis presents with nephritic syndrome. Microscopy reveals inflammation and immune-complex deposits, whereas immunofluorescence reveals granular IgG and C3.
There is no such thing as primary post-infectious glomerulonephritis: it is always secondary to infection (hence the "post-infectious" in the name). As mentioned before, it is usually due to Streptococcus, but not always. Prognosis is very good in children, with nearly all children recovering with only conservative treatment. However, prognosis is not so good in adults: around 40% of adults with post-infectious glomerulonephritis progress to chronic renal failure.
Crescentic glomerulonephritis
As mentioned earlier, crescentic glomerulonephritis is a subset of glomerulonephritis that can present with rapidly progressive glomerulonephritis (a subset of nephritic syndrome). Crescentic glomerulonephritis is not a diagnosis- it is simply a histological pattern with an underlying cause that needs to be identified.
The "crescents" in crescentic glomerulonephritis are formed by a proliferation of parietal epithelial cells, which are epithelial cells lining Bowman's capsule. The crescents can fill up Bowman's space and block it, leading to chronic renal failure within weeks to months. There are three main categories of crescentic glomerulonephritis. Type I crescentic glomerulonephritis is characterised by anti-glomerular basement membrane (anti-GBM) autoantibodies, type II is immune complex mediated, and type III is "pauci-immune" (which I think means that there is minimal evidence of hypersensitivity).
Type I crescentic glomerulonephritis
Type I crescentic glomerulonephritis, or anti-GBM disease, involves autoantibodies against the α3 chain of the Type IV collagen in the glomerular basement membrane. These autoantibodies may cross-react with the basement membranes of other tissues, notably in the lung, resulting in a syndrome called pulmonary-renal syndrome. Pulmonary-renal syndrome is also known as Goodpasture syndrome.
Type II crescentic glomerulonephritis
Type II crescentic glomerulonephritis is immune-complex mediated and includes several types of glomerulonephritis that I've already written about above, including post-infectious glomerulonephritis and IgA nephropathy.
Type III crescentic glomerulonephritis
Type III crescentic glomerulonephritis, or pauci-immune glomerulonephritis, involves an antibody called ANCA. ANCA stands for anti-neutrophil cytoplasmic antibody, and as the name suggests, it acts against cytoplasmic enzymes in neutrophils. Type III crescentic glomerulonephritis is associated with small-vessel vasculitis, including Wegener's granulomatosis (a.k.a. granulomatosis with polyangiitis, or GPA), and Churg-Strauss syndrome (a.k.a. eosinophilic granulomatosis with polyangiitis, or EGPA). GPA involves necrotising granulomatous inflammation of the respiratory tract and kidney. EGPA is similar, but there may also be asthma and eosinophil-rich granulomas.
This lecture was long, but it only had one learning outcome: "Classify glomerulonephritis with reference to aetiology, pathogenesis, clinical presentation, key morphological findings and natural history." I will be using my own headings for this post instead.
Clinical Presentations of Renal Disease
There are four (or five, depending on how you count them) main presentations of renal disease: acute renal failure, chronic renal failure, nephritic syndrome, and nephrotic syndrome. There is also rapidly-progressing glomerulonephritis, which is a subset of nephritic syndrome. Renal diseases are very common: around 40% of adults over 75 will have indicators of chronic kidney disease, and this number is even higher in Indigenous populations.
Acute renal failure
Acute renal failure is characterised by azotaemia, which is a rapid rise in serum urea and/or creatinine (a marker of renal function). There may also be uraemia, which is essentially just symptomatic azotaemia (symptoms include lethargy, decreased appetite, shortness of breath, peripheral neuropathy, and oedema). Other symptoms include oliguria (reduced urine output), or maybe even anuria (no urine output). Symptoms arise over days to weeks and may completely resolve (though there is a chance of progressing to chronic renal failure).
Causes of renal failure can be classified into three categories: pre-renal, renal, and post-renal. Pre-renal causes encompass basically anything that affects the blood supply to the kidneys. Renal failure encompasses intrinsic kidney diseases, and post-renal causes encompass anything that affects urine outflow.
Chronic renal failure
Chronic renal failure is basically the same as acute renal failure, but it is over a longer period of time (months to years). Furthermore, chronic renal failure is irreversible and will eventually progress to end-stage renal failure, defined as a glomerular filtration rate of less than 5% of normal. Treatment of chronic renal failure aims to delay progression.
Nephritic syndrome
Nephritic syndrome is a set of symptoms that includes azotaemia/uraemia, oliguria, macroscopic haematuria (blood in the urine that you can see), mild/moderate proteinuria, and hypertension. It is usually caused by glomerulonephritis (disease that affects the glomerulus). Rapidly-progressive glomerulonephritis (RPGN) is a subset of nephritic syndrome in which the rise in serum urea and creatinine is very rapid. RPGN is usually due to a subset of glomerulonephritis called crescentic glomerulonephritis.
Nephrotic syndrome
Nephrotic syndrome is a set of symptoms that includes proteinuria (>3.5g/24h), hypoalbuminaemia, peripheral oedema, hyperlipidaemia, and lipiduria. Nephrotic syndrome, like nephritic syndrome, is usually due to glomerulonephritis. If glomerulonephritis increases the permeability of glomerular capillaries, proteins can leak out into the urine, resulting in proteinuria. Since protein is leaving the body through the urine, there is low protein in the serum, leading to hypoalbuminaemia and a reduced serum oncotic pressure, which in turn can lead to peripheral oedema. At the same time, there is increased hepatic lipid synthesis, leading to hyperlipidaemia and eventually lipiduria.
Glomerulonephritis
I've mentioned glomerulonephritis before, but what is it exactly? Well, glomerulonephritis refers to a range of diseases that affect the glomeruli of the kidneys. Most of these diseases are mediated by the formation of immune complexes or structural issues. Diagnostic tools for glomerulonephritis include light microscopy, immunofluorescence, and electron microscopy. Glomerulonephritis can be iether primary or secondary: primary glomerulonephritis has no identifiable cause, whereas secondary glomerulonephritis is due to a recognisable cause (e.g. drugs, infections, etc.).
Glomerulonephritis can present in different ways, depending on the specific disease. Some types of glomerulonephritis have a presentation resembling nephrotic syndrome, whereas others have a presentation resembling nephritic syndrome. In this post, I'll be starting with the most "nephrotic" types of glomerulonephritis and working my way towards the most "nephritic" types of glomerulonephritis.
Minimal change disease
Minimal change disease is a type of glomerulonephritis that mainly affects children and presents with nephrotic syndrome. It is a disease mediated by structural changes, in particular of the podocytes surrounding glomerular capillaries. As you can guess by the name, there are minimal changes in the diagnostic tests. Light microscopy and immunofluorescence both look normal: you have to use electron microscopy to see the difference. Normal podocytes have "slit diaphragms" between the foot processes, and these "slit diaphragms" have the negative charge that repels proteins and stops them from getting into the urine. In minimal change disease, foot processes are effaced and fused together, meaning that the slit diaphragms and the repulsive negative charge are lost, allowing proteins to leak into the urine, resulting in nephrotic syndrome.
Prognosis of minimal change disease is very good in children, as it responds well to steroids in this population. The response in adults, however, is less predictable.
Membranous nephropathy
Membranous nephropathy mainly affects adults and results in nephrotic syndrome. It is mediated by immune complexes that deposit in the subepithelial space (i.e. under the podocytes but outside the basement membrane... I think). Basement membrane "spikes" (thickening of the basement membrane) appear between the deposits of immune complexes. Immunofluorescence shows granular IgG and C3.
Unlike with other forms of glomerulonephritis, primary membranous nephropathy now has an identifiable cause. Primary membranous nephropathy is due to autoantibodies to the podocyte phospholipase A2 receptor. Secondary membranous nephropathy can be all the usual suspects: drugs, infections, autoimmune diseases, etc.
Prognosis of membranous nephropathy is quite variable. 40% of patients will go into pontaneous remission. However, 40% of patients will progress to chronic renal failure. The remaining 20% of patients will have stable disease.
Focal segmental glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis (FSGS) is focal, meaning that less than 50% of all glomeruli are affected, and segmental, meaning that less than 50% of an individual glomerulus is affected. (Just for comparison: diffuse means that more than 50% of all glomeruli are affected, whereas global means that more than 50% of individual glomeruli are affected). FSGS is the most common cause of nephrotic syndrome in adults and is due to structural abnormalities in the podocytes.
As the "sclerosis" part of the name suggests, there is scarring involved in FSGS. Scarring can be seen under both light and electron microscopy. FSGS is not immune-mediated, but due to scarring, larger antibodies such as IgM may be trapped and can be identified under immunofluorescence. Sometimes, complement molecules such as C3 may be also be activated by the trapping of IgM.
Prognosis of FSGS is not the worst, but it's not the best either. Around 30% of patients respond to steroids, but the rest progress to chronic renal failure.
IgA nephropathy (a.k.a. Berger's disease)
IgA nephropathy is the most common cause of glomerulonephritis worldwide and usually affects young adults. It is immune-complex mediated and presents with nephritic syndrome (note: this is the first type of glomerulonephritis I've spoken about so far that presents with nephritic, rather than nephrotic, syndrome). Under light microscopy, there is mesangial matrix expansion and hypercellularity, and under electron microscopy, the immune-complexes can be seen. Immunofluorescence reveals granular IgA (hence why this disease is called IgA nephropathy).
Prognosis of IgA nephropathy follows the "Rule of Thirds": around 1/3 resolve spontaneously, 1/3 have stable disease, and 1/3 progress to FSGS and/or chronic renal failure.
Post-infectious glomerulonephritis (a.k.a. acute proliferative glomerulonephritis or post-streptococcal glomerulonephritis)
Post-infectious glomerulonephritis usually affects children around 1-4 weeks after a bout of cellulitis or pharyngitis. It is immune-complex mediated and is often a response to streptococcal pyrogenic exotoxin B, which is why this disease is sometimes called post-streptococcal glomerulonephritis. (Note, however, that Streptococcus species are not the only species that can cause this disease.) Post-infectious glomerulonephritis presents with nephritic syndrome. Microscopy reveals inflammation and immune-complex deposits, whereas immunofluorescence reveals granular IgG and C3.
There is no such thing as primary post-infectious glomerulonephritis: it is always secondary to infection (hence the "post-infectious" in the name). As mentioned before, it is usually due to Streptococcus, but not always. Prognosis is very good in children, with nearly all children recovering with only conservative treatment. However, prognosis is not so good in adults: around 40% of adults with post-infectious glomerulonephritis progress to chronic renal failure.
Crescentic glomerulonephritis
As mentioned earlier, crescentic glomerulonephritis is a subset of glomerulonephritis that can present with rapidly progressive glomerulonephritis (a subset of nephritic syndrome). Crescentic glomerulonephritis is not a diagnosis- it is simply a histological pattern with an underlying cause that needs to be identified.
The "crescents" in crescentic glomerulonephritis are formed by a proliferation of parietal epithelial cells, which are epithelial cells lining Bowman's capsule. The crescents can fill up Bowman's space and block it, leading to chronic renal failure within weeks to months. There are three main categories of crescentic glomerulonephritis. Type I crescentic glomerulonephritis is characterised by anti-glomerular basement membrane (anti-GBM) autoantibodies, type II is immune complex mediated, and type III is "pauci-immune" (which I think means that there is minimal evidence of hypersensitivity).
Type I crescentic glomerulonephritis
Type I crescentic glomerulonephritis, or anti-GBM disease, involves autoantibodies against the α3 chain of the Type IV collagen in the glomerular basement membrane. These autoantibodies may cross-react with the basement membranes of other tissues, notably in the lung, resulting in a syndrome called pulmonary-renal syndrome. Pulmonary-renal syndrome is also known as Goodpasture syndrome.
Type II crescentic glomerulonephritis
Type II crescentic glomerulonephritis is immune-complex mediated and includes several types of glomerulonephritis that I've already written about above, including post-infectious glomerulonephritis and IgA nephropathy.
Type III crescentic glomerulonephritis
Type III crescentic glomerulonephritis, or pauci-immune glomerulonephritis, involves an antibody called ANCA. ANCA stands for anti-neutrophil cytoplasmic antibody, and as the name suggests, it acts against cytoplasmic enzymes in neutrophils. Type III crescentic glomerulonephritis is associated with small-vessel vasculitis, including Wegener's granulomatosis (a.k.a. granulomatosis with polyangiitis, or GPA), and Churg-Strauss syndrome (a.k.a. eosinophilic granulomatosis with polyangiitis, or EGPA). GPA involves necrotising granulomatous inflammation of the respiratory tract and kidney. EGPA is similar, but there may also be asthma and eosinophil-rich granulomas.
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