Pathology 1 Congenital & Cystic diseases of the kidney Dr. Najla a Aldaoud Omar Ayman Khasawneh 1 P a g e
Slides are included بسم هللا الرحمن الرحيم Today is our first pathology lectures, Dr Najla' will give us medical kidney diseases in the first six lectures, then Dr Samer will follow her to give us lectures about bladder, renal tumors, prostate, male genital, lastly we will take female genital & breast with Dr Alia. Lectures contents ; we will discuss with Dr Najla' ; glomerular diseases, tubulointerstitial diseases (tubular and interstitial diseases are grouped together bcz the diseases affect them both at same time bcz interstitium is the CT in b/w the tubules), vascular diseases, congenital anomalies and part of infections. The other part of infections and neoplastic diseases will be discussed by Dr Samer. Just to summarize things we will go a little bit over the anatomy and physiology of the kidney. Anatomy &Histology The kidney is divided into cortex and medulla then we have the calyces(minor and major) then the renal pelvis then the ureter (which is continuation of renal pelvis) ; now each one of those compartments have its own type of disease that affect them ; we have diseases that affect renal cortex while others affect renal pelvis and ureter, and so on. The main functioning unit of the kidney is nephron which is composed of glomerulus (its tuft of capillaries with two poles "vascular & urinary"), so as the blood is coming to glomerulus through the afferent arterioles of the vascular pole it will be 2 P a g e
filtered and the substances which has been filtered will go through the urinary pole to proximal tubules then loop of Henle (descending and ascending) then the distal tubules and then to the collecting ducts. *Note : The functioning units of the kidney : (1) nephron (2) collecting ducts These are the distal convoluted tubules ; their characteristics (smaller lumen, less in number, pale cytoplasm "not eosinophilic" ) These are the proximal convoluted tubules ; their characteristics (large lumen, more abundant, eosinophilic cytoplasm ) This is the glomerulus ; it's composed of : 1.endothelial cell 2.basement membrane 3.mesangial cells and mesangial matrix (mes.. mid // angeion..vessel "BVs") ; they are in b/w the afferent and efferent arterioles & they are the main cells of the glomerulus 4. Podocytes ; they are the epithelial lining of visceral layer of bowman's space, we can't see them on H&E stain 5.the epithelial cells of the parietal layer of bowman's space ; we can see them on H&E stain *Note : Bowman's capsule composed of parietal and visceral layer ; & in b/w them the bowman's space Podocytes are on visceral layer This picture for illustrative purposes only & it's not from our slides 3 P a g e
Physiology The kidney is complex organ that carry out many functions : 1. Excretion of waste products of metabolism ( this is the main function of the kidney ) 2. Regulation of body water and salt 3. Maintenance of appropriate acid balance &secretion of variety of hormones Now, we end up talking about anatomy and physiology, more details will be discussed in their lectures, so we will start with actual pathology. What is the importance of renal diseases? Actually, the renal diseases are NOT major cause of death, so if we compare the death rates in US ; we will find that the major cause of death is the heart diseases (strokes, MI ) and of course the cancers. These are the statistics from USA : RENAL -------------- 70,000 deaths / year (USA) HEART -------------- 700,000 = CANCER ------------ 550,000 = = (USA) = (USA) STROKES -----------170,000 = = (USA ) The renal diseases per se cause death, but not as much as heart & cancer, so their importance comes from the fact that they have a great deal of morbidity ; so if the pt has (UTI, stones) ; he will be in pain and if the pt has chronic stones he might suffer from (obstructive uropathy), the pt with renal failure will go for dialysis so he will stuck to that machine for 3hrs 3 times / week & that s really disabling. as well, the pts of young age group with renal diseases will develop in future chronic renal failure and that will be the cause of death for them. >>> the underlined sentences are answer for the question. (what is the importance of renal diseases) *Note : The treatment of chronic renal failure : 1.Dialysis 2.Kidney transplant 4 P a g e
Classification of renal diseases based on the site of involvement : [glomerular diseases, tubulointerstitial diseases, vascular diseases] ; all of them at the end stage will lead to chronic renal failure & at that stage it will be difficult to know what is the cause of chronic renal failure (bcz the kidney will have obsolete glomeruli, tubular and vascular changes) ; so its important to catch the disease as early as possible to know the etiology and treat it. *Note : The same thing was applied to the liver ; if we catch the disease early we can know the cause of liver injury BUT once the liver reach to level of cirrhosis we can't know the cause. Congenital anomalies of the kidney: Agenesis and Hypoplasia Agenesis : kidney was not formed from the beginning. it can be bilateral or unilateral. If its bilateral the pts are incompatible with life so they will die in utero or soon after delivery, BUT if it's unilateral it will be an incidental finding (bcz one kidney will take over the function of the other kidney ; so the person will be ok) and it's common. Hypoplasia : the kidney is there but it's smaller than the normal size ((number of nephrons, size of kidney, and weight of kidney) will be less than normal). it might be unilateral or bilateral, it will lead to chronic renal failure in childhood especially if the pt is having bilateral hypoplasia. Ectopic kidney and horseshoe kidney Ectopic kidney : the kidney will not be placed in its normal site (normally it's retroperitoneal in the flank) mostly it will be placed in site lower than the normal site as the pelvic brim at the pelvis. It's an incidental finding (during operation or ultrasound for whatever reason) The main complications of this are obstructive uropathy which means the ureters will be more liable to have obstruction and formation of stones. Horseshoe kidney : it means fusion of both kidneys at the midline so they will be as U-shaped. 5 P a g e
Again the ureters will not be placed in their position so they are easily kinked, thus lead to obstruction and eventually they will be more liable for stones formation. Congenital cystic diseases of the kidney 1.childhood polycystic kidney disease 2.adult polycystic kidney disease <<will be discussed later in this sheet>> *Note : Whenever we find a congenital anomaly in the kidney we have to exclude the presence of another one in a site related to it (i.e. : in UGS). Cystic diseases of the kidney : It s a big list of heterogeneous group of hereditary, acquired and developmental disorders, which include : Acquired >> 1. Simple renal cyst 2. Acquired dialysis associated cystic disease ; the kidney was normal but as result of dialysis for long period of time the kidney will undergo cystic changes. Hereditary>> 1. Cystic renal dysplasia ; non functioning kidney at early age 2. polycystic kidney diseases (childhood &adult types) 3. Medullary sponge kidney 4. Nephronophthisis ; its uremic medullary cystic disease complex Now the question is why cystic renal diseases are important? It's reasonably common ; for example the pt did an ultrasound & we find a renal cyst ; so we have to know ; is it normal or not?, is it neoplastic, acquired or hereditary? ; so we have to know the answer bcz each answer has different management. 6 P a g e
It is usually present diagnostic problems for clinician, radiologist & pathologist. Some of them such as autosomal dominant polycystic kidney disease (adult type) are very important bcz they are common in our community ; we have one case of adult polycystic kidney disease in 500 and they are the major cause of chronic renal failure *Note: the pts with polycystic kidney disease will go ultimately to chronic renal failure ; it's only matter of years. To differentiate them from malignant tumors ; bcz some of malignant tumors in the kidney can have cystic component. Acquired : 1. Simple renal cyst : It s the most common cyst that will affect the kidneys ; and we know that from autopsy studies from western countries ; so it's an incidental finding & the pt will not have any complaints. So, it can be single or multiple, its size range from 1-5 cm, and as we said its common postpartum finding without clinical significance but occasionally it will produce symptoms in case of (hemorrhage inside it, if its enlarged "it will lead to stretching the renal capsule" and if its ruptured ). Again, the most important thing is to differentiate them from renal tumors and NOT to misdiagnose them with the renal neoplasm. This is an example of multiple simple renal cysts ( four cysts can be seen here) They are unilocular ( one type of cells lining the cyst) and the cysts contain clear fluid. 7 P a g e
2. Acquired renal cystic disease : It's occurred in pts who remain on dialysis for long period of time (to manage their actual disease which is chronic renal failure ), usually it's asymptomatic but sometimes the pts will have hematuria. the most ominous complication is the development of renal cell carcinoma in the cyst wall(its relative risk is about 7% over 10yrs of dialysis) This is renal cell CA arising in pt who is having acquired renal cystic disease (notice that the whole kidney was replaced by cysts "cortical & medullary" cysts ) Hereditary : The pathophysiology of hereditary cystic diseases ;1 st theory : mutations in polycystin 1,2"adult type" or fibrocystin "childhood type" will lead to some problem in cell-cell &cell-matrix interactions that will affect the tubular epithelial growth and differentiation, so if that affected thus will lead to cell proliferation, abnormal extracellular matrix, fluid secretion inside the tubules and the end result is expansion & cyst formation ; all these changes will lead to vascular damage, interstitial fibrosis & inflammation. This is a summary for what we have said. 8 P a g e
2 nd theory ; it s a recent theory suggests that there is an abnormality in cilia centrosome complex of tubular epithelial cells (actually cilia centrosome complex is like a mechanosensors to feel the amount of fluid inside the tubules) ; so it seems that the mutation in polycystin gene will affect the mechanosensors & will lead to interference with fluid absorption & cellular maturation and ultimately will lead to cyst formation. We call this "Ciliopathy". 1. Adult polycystic kidney disease "APKD" ; it's an autosomal dominant, we call it adult bcz the manifestation will occur during adulthood (so the kidneys at the beginning were normal). 2. Childhood polycystic kidney disease "CPKD" ; it's an autosomal recessive ; we call it childhood bcz the pt will be delivered with cysts inside his kidneys. Its an autosomal dominant, in this entity the pt will have multiple expanding cysts in both kidneys that will eventually destroy the intervening parenchyma, so usually those babies are delivered normal (their kidneys have nothing in them) but a long the years there will be cyst formation which affect both cortex and medulla so it will cause atrophy of the functioning kidney. It will take at least 40yrs before the pt comes for medical intervention ; bcz the manifestation will not appear till the whole functioning kidney has been vanished. As we said its common (1 per 500-1000), & it's responsible for about 10% of pts with chronic renal failure. Mutations usually occur in PKD gene which encodes for polycystin protein : 1- PKD1 on chr(16) encodes for polycystin 1, & it s the most common mutation ( 90% of cases) 2- PKD2 on chr(4) encodes for polycystin 2, & it s the next common one (10% of cases) 3- PKD3 in very few cases. Morphology : it's bilateral, so both kidneys will be enlarged and reached up to 4Kg! (normal kidney weight is about 150gm). also there will be numerous cysts varying in size and affecting both cortex and medulla, & these cysts usually will be filled with clear fluid but sometimes we can find hemorrhage inside them. 9 P a g e
Clinical features : Gradual onset of chronic renal failure The pts will be liable for infections(uti) and stones formation ; bcz we have a stagnant fluid inside the cysts Flank pain and dragging sensation bcz the pt has very enlarged kidneys so he will feel dragging pain his flank. It can lead to intermittent gross hematuria 75% of those pts will suffer from HTN mostly due to chronic renal failure. *Note : the renal failure can lead to HTN, also, the HTN can lead to renal failure. In APKD the chronic RF lead to HTN. They found also in those pts that they are not liable to have cysts in the kidneys only, but they also can have cysts in liver and pancreas ; so we can see liver cysts in 40% of the cases. 10-30% of those pts will have berry aneurysms (which we took in CNS) & it's on of the common causes of their death ; so if it's ruptured thus lead to subarachnoid hemorrhage & those pts will die bcz of intracranial hemorrhage. As we can see it s a huge kidney, all of the parenchyma is replaced by variable sized cysts, and we can see a stone inside on of those cysts. *Note : If we have cysts the first thing we have to know ; is it bilateral or unilateral? ; bcz bilateral usually is a hereditary while unilateral will be something else. APKD is an AD and a lot of relatives are marrying each other so if we pick it up we have to consult those parents bcz there will be a higher probability to transfer the ds to their children. 10 P a g e
This autopsy for a pt who had APKD with involvement of both kidneys & he had undergone kidney transplant bcz of his chronic RF. *Note : kidney transplantation in pts with chronic RF bcz of APKD will be better prognosis than in pts with chronic RF bcz of glomerulonephritis disease ; bcz in the latter there will be high rate of recurrence. It's an autosomal recessive, usually its present early in life & some of them can even die in utero (stillbirth). It also eventually will lead to chronic renal failure It affects certain parts of the kidney (unlike APKD which affect the whole kidney) ; so here it will affect the collecting tubules peculiarly ; and that s why on examination before opening the kidney, it has a smooth kidney surface bcz PCT,DCT & glomeruli are not involved.(unlike APKD which we can easily differentiate it even before open the kidney bcz it will be as a bag of cysts). The cystic dilated tubules will have a certain arrangement ; so they will be perpendicular to the surface. Nearly all cases are associated with liver cysts. *Note : both APKD & CPKD are associated with liver cysts,but they are more common with CPKD. The pts with mild form of this disease their renal function will be ok but they will suffer later on from another entity which is congenital hepatic fibrosis (we took it in GI). Its resulted from mutation in PKHD1 on chr(6) which encodes for fibrocystin (from book NOT mentioned in slides) 11 P a g e
A : this is APKD bcz we can see from external surface of the kidney before opening it we have multiple cysts bulging out B : this is across section from A C : this is CPKD (AR) ; bcz the kidney has smooth surface since the involved part is the collecting ducts not the whole kidney D : this is a liver cyst in a pt with CPKD(AR) This is an example of CPKD in very young pt ; we can see the dilated channels perpendicular to the cortex. 12 P a g e
Here is the histology of CPKD ; we can see that there are the collecting tubules dilated & they are arranged perpendicular to the renal cortex & nothing is bulging outside (smooth surface) DONE Here I'm done with my sheet, this is the last module in our basic years hoping for you happy end. GOOD LUCK in our next clinical years. Your colleague : Omar Ayman Khasawneh 13 P a g e