Friday [nephrology] Flashcards
(113 cards)
1
Q
Anatomical position/size of the kidneys
A
The kidneys lie retroperitoneally (behind the peritoneum) in the abdomen, either side of the vertebral column.
They typically extend from T12 to L3, although the right kidney is often situated slightly lower due to the presence of the liver. Each kidney is approximately three vertebrae in length
2
Q
How are the adrenal glands separated from the kidneys?
A
The adrenal glands sit immediately superior to the kidneys within a separate envelope of the renal fascia
3
Q
What are the layers of the kidney?
A
Renal capsule – tough fibrous capsule.
Perirenal fat – collection of extraperitoneal fat.
Renal fascia (also known as Gerota’s fascia or perirenal fascia) – encloses the kidneys and the suprarenal glands.
Pararenal fat – mainly located on the posterolateral aspect of the kidney.
4
Q
Label the layers of the kidney here
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A
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5
Q
How can the renal parnechyma be subdivided?
A
Internally, the kidneys have an intricate and unique structure. The renal parenchyma can be divided into two main areas – the outer cortex and inner medulla
6
Q
How does the medulla divide in the kidneys?
A
The cortex extends into the medulla, dividing it into triangular shapes – these are known as renal pyramids.
7
Q
What is the apex of the renal pyramid called? And what is each of these associated with?
A
The apex of a renal pyramid is called a renal papilla. Each renal papilla is associated with a structure known as the minor calyx, which collects urine from the pyramids. Several minor calices merge to form a major calyx.
8
Q
Where does the urine pass through in the kidneys
A
Urine passes through the major calices into the renal pelvis, a flattened and funnel-shaped structure. From the renal pelvis, urine drains into the ureter, which transports it to the bladder for storage
9
Q
Label the kidney parts here
A
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10
Q
Name a structure that is anterior/posterior to each kidney
A
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11
Q
Main arterial supply of the blood to the kidneys
A
The kidneys are supplied with blood via the renal arteries, which arise directly from the abdominal aorta, immediately distal to the origin of the superior mesenteric artery. Due to the anatomical position of the abdominal aorta (slightly to the left of the midline), the right renal artery is longer, and crosses the vena cava posteriorly
12
Q
What happens to the renal artery as it enters the hilum?
A
The renal artery enters the kidney via the renal hilum. At the hilum level, the renal artery forms an anterior and a posterior division, which carry 75% and 25% of the blood supply to the kidney, respectively.
13
Q
What happens to the anterior and posterior divisions of the kidneys
A
Five segmental arteries originate from these two divisions
14
Q
What is the avascular plane of the kidney and what is it significant?
A
The avascular plane of the kidney (line of Brodel) is an imaginary line along the lateral and slightly posterior border of the kidney, which delineates the segments of the kidney supplied by the anterior and posterior divisions. It is an important access route for both open and endoscopic surgical access of the kidney, as it minimises the risk of damage to major arterial branches
15
Q
Why is the fact that renal artery branches are anatomical end arteries matter?
A
The renal artery branches are anatomical end arteries – there is no communication between vessels. This is of crucial importance; as trauma or obstruction in one arterial branch will eventually lead to ischaemia and necrosis of the renal parenchyma supplied by this vessel
16
Q
Bonus: how does the segmental arteries undergo further divisions?
A
The segmental branches of the renal undergo further divisions to supply the renal parenchyma:
Each segmental artery divides to form interlobar arteries. They are situated either side every renal pyramid.
These interlobar arteries undergo further division to form the arcuate arteries.
At 90 degrees to the arcuate arteries, the interlobular arteries arise.
The interlobular arteries pass through the cortex, dividing one last time to form afferent arterioles.
The afferent arterioles form a capillary network, the glomerulus, where filtration takes place. The capillaries come together to form the efferent arterioles.
17
Q
What is the peritubular network of the renal cortex?
A
In the outer two-thirds of the renal cortex, the efferent arterioles form what is a known as a peritubular network, supplying the nephron tubules with oxygen and nutrients
18
Q
What is the inner third of the cortex and medulla supplie dby?
A
The inner third of the cortex and the medulla are supplied by long, straight arteries called vasa recta.
19
Q
Label the large vessels of the kidney
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A
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20
Q
Describe how the arterial supply of the kidney can be divided into 5 segments
A
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21
Q
Why is there often variation in the arterial supply of the kidney?
A
The kidneys present a great variety in arterial supply; these variations may be explained by the ascending course of the kidney in the retroperitoneal space, from the original embryological site of formation (pelvis) to the final destination (lumbar area). During this course, the kidneys are supplied by consecutive branches of the iliac vessels and the aorta.
Usually the lower branches become atrophic and vanish while new, higher ones supply the kidney during its ascent. Accessory arteries are common (in about 25% of patients). An accessory artery is any supernumerary artery that reaches the kidney. If a supernumerary artery does not enter the kidney through the hilum, it is called aberrant.
22
Q
What type of arteries of common [in about 25% of patients]?
A
Accessory arteries
23
Q
Label this diagram of variation of arterial supply kidney
A
image
24
Q
Describe the venous drainage of the kidney
A
The kidneys are drained of venous blood by the left and right renal veins. They leave the renal hilum anteriorly to the renal arteries, and empty directly into the inferior vena cava.
As the vena cava lies slightly to the right, the left renal vein is longer, and travels anteriorly to the abdominal aorta below the origin of the superior mesenteric artery. The right renal artery lies posterior to the inferior vena cava.
25
Describe the lymphatics of the kidney
Lymph from the kidney drains into the lateral aortic (or para-aortic) lymph nodes, which are located at the origin of the renal arteries.
26
Give two congenital abnormalities of the kidneys
Pelvic kidney
| Horseshoe kidney
27
What is a pelvic kidney?
In utero, the kidneys develop in the pelvic region and ascend to the lumbar retroperitoneal area. Occasionally, one of the kidneys can fail to ascend and remains in the pelvis – usually at the level of the common iliac artery
28
What is a horseshoe kidney?
A horseshoe kidney (also known as a cake kidney or fused kidney) is where the two developing kidneys fuse into a single horseshoe-shaped structure.
This occurs if the kidneys become too close together during their ascent and rotation from the pelvis to the abdomen – they become fused at their lower poles (the isthmus) and consequently become ‘stuck’ underneath the inferior mesenteric artery.
This type of kidney is still drained by two ureters (although the pelvices and ureters remain anteriorly due to incomplete rotation) and is usually asymptomatic, although it can be prone to obstruction.
29
Common tumour found in kidneys
The kidney is often the site of tumor development, most commonly renal cell carcinoma.
30
How is a partial nephrectomy performed in the context of RCC?
Due to the segmental vascular supply of the kidney it is often feasible to ligate the relative arteries and veins and remove the tumour with a safe zone of healthy surrounding parenchyma (partial nephrectomy) without removing the entire kidney or compromising its total vascular supply by ischaemia.
31
Role of the kidneys
1. Regulation of extracellular fluid volume and pressure
2. Regulation of osmolarity
3. Maintenance of ion balance
4. Homeostatic regulation of pH
5. Excretion of waste
6. Production of hormones
7. Gluconeogenesis
32
Anatomy of the nephron
Afferent arteriole -> Bowman's capsule [in the glomerulus] -> Efferent arteriole
Proximal convuluted tubule -> Loop of Henle [descending then ascending] -> distal convoluted tubule -> collecting duct
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33
label these cells in the bowman's capsule
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34
Describe function of podocytes, mesenglial cells , macula densa cells and granular cells
Podocytes - filtration of substances from capilaries to the neprons
Mesenchyl cells - contraction and altering blood flow
Granular cells - mechanoreceptors that secrete renin
Mesenglial cells outisde nephron - lots of actin to alter bf
Macula densa cells - chemorecpetors that monitor NaCl content going to the DCT
35
What makes up the renal corpuscle?
glomerulus and glomerulus apsule
36
What's in the juxtaglomerular complex?
Macula densa cells, granula cells, meseglial cells
37
What are the three major renal processes?
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38
How to calculate the amount of solute excreted [solute in pee]?
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39
What is the role of the early DCT?
The role of the early DCT is the absorption of ions, including sodium, chloride and calcium. It is impermeable to water.
40
Which cells are situated in the first segment of the DCT?
The macula densa are situated in the first segment of the DCT – these are the sensing epithelium involved in tubuloglomerular feedback. This tubuloglomerular feedback allows for control of glomerular filtration rate (GFR) and blood flow within the same nephron
41
Which transporters are active in the movement of ions at the DCT?
Movement of these ions is dependent on the Na+/K+-ATPase transporter on the basolateral membrane of the cells. This excretes sodium ions into the extracellular fluid, and brings potassium ions into the cell. This channel reduces intracellular sodium levels, creating a gradient which favours movement of sodium into the cell via other channels on the apical membrane. This process is primary active transport, as ATP is directly needed to set up the gradient.
The sodium concentration gradient generated allows sodium to enter the cell from the lumen of the distal convoluted tubule, which occurs through the NCC symporter (sodium-chloride cotransporter), alongside chloride ions. The chloride ions then exit the cell through a chloride ion uniporter on the basolateral membrane into the extracellular fluid, preventing accumulation within the cell.
42
Which drugs used to treat HTN and HF inhibit the NCC transporter?
Thiazide diuretics, used to treat hypertension and heart failure, inhibit the NCC.
43
Which other ion uses the sodium gradient?
Calcium (Ca2+) absorption also utilizes the sodium gradient established from the Na+/K+-ATPase channel. On the basolateral membrane, there is also an NCX channel (sodium-calcium antiporter). This is responsible for transporting calcium ions out into the extracellular fluid, and sodium ions into the cell. The reduction in intracellular calcium creates a gradient which draws calcium ions from the lumen of the tubule into the cell, through a calcium ion uniporter. Since ATP is not directly required, this is secondary active transport
44
Which other hormone works on calcium absorption?
Parathyroid hormone (PTH) also acts here – binding of PTH to its receptor causes more Ca2+ channels to be inserted and increases Ca2+ reabsorption.
image
45
What are the two main cell types in the late DCT and CD?
There are two main cell types in this region: principal cells and intercalated cells.
46
Main function of principle cells
Principal cells make up the majority of the tubular cells. They are mainly involved in the uptake of sodium ions and extrusion of potassium ions.
47
How the principle cells carry out their function
This exchange is, again, driven by a Na+/K+-ATPase on the basolateral membrane This sets up a gradient for sodium to enter the cell through ENaC channels (epithelial Na+ channel).
Sodium ions are positively charged, so as they are extruded an electrical gradient is formed. Additionally, potassium ions accumulate within the cell due to the Na+/K+-ATPase. Both of these factors promote secretion of potassium ions into the lumen of the tubule through a potassium uniporter.
48
Type of intercalated cells?
Type A and type B
49
How do type A intercalated cells work?
Intercalated cells assist in acid-base control, by controlling the levels of hydrogen (H+) and bicarbonate ions (HCO3–). Type A intercalated cells utilise hydrogen-ATPase and H+/K+-ATPase transporters to secrete H+ into the lumen, whilst reabsorbing HCO3–. Bicarbonate is formed intracellularly by carbonic anhydrase acting on carbon dioxide and water (similarly to in the PCT). The difference between the PCT and type A intercalated cells, is that these cells can actively secrete H+ into the lumen against a large concentration gradient, allowing for H+ secretion in response to acidosis. Once in the lumen of the tubule, the hydrogen ions react with either phosphate (HPO42-) or ammonia (NH3). This prevents the ions from re-entering the cell, as both new compounds (NH4+ and H2PO4–) are charged. Hence, they are unable to travel back across the membrane, and so are excreted.
To prevent an accumulation of chloride ions and potassium ions within the cell, a K+/Cl– symporter on the basolateral membrane allows leakage of these ions back into the extracellular fluid.
50
How do type B intercalated cells work?
Conversely, type B intercalated cells have H+ and HCO3– channels on opposite sides of the cell. The net effect in type B cells is secretion of HCO3– and reabsorption of H+, important in the body’s response to alkalosis.
51
What is the main role of the CD?
The main role of the collecting duct is the reabsorption of water, through the action of anti-diuretic hormone (ADH) and aquaporins.
52
Where does ADH act?
ADH is produced in the hypothalamus, and stored in the posterior pituitary gland until it is released. This hormone acts on kidney tubules to increase the number of aquaporin 2 channels (water channels) in the apical membrane of collecting duct tubular cells.
53
How does ADH work?
ADH binds to V2 receptors on the tubule cells, which activate adenylyl cyclase hence increasing production of cyclic AMP. Subsequently, vesicles containing the aquaporin 2 channels deposit their contents into the apical membrane of the tubular cells (the basolateral membrane always contains aquaporin 3 and 4 channels, so is always permeable). Increasing the number of channels increases the permeability of the cell, resulting in the ability to reabsorb more water from the filtrate and create smaller volumes of more concentrated urine.
54
How does ADH act in the urea cycle?
Increase urea reabsorption in the medullary collecting duct
55
Where does ADH act on the nephron for the urea cycle?
The thick ascending limb of the nephron is impermeable to water, but permeable to urea. This means that the urea is able to pass from the interstitium back into the thick ascending limb down its concentration gradient (urea recycling). Whilst in the interstitium, urea acts as an effective osmole and hence allows greater volumes of water to be reabsorbed in the nephron.
56
What is SiADH?
This syndrome is where excessive ADH is released. As a result, there is increased aquaporin expression in the collecting duct and excess water retention.
57
What does excess water retention in SiADH cause?
The excessive dilution of blood lowers the sodium concentration and causes hyponatraemia, presenting with symptoms such as nausea, vomiting and lethargy. Aldosterone secretion is also decreased in response to fluid retention, further reducing sodium uptake in the kidney and thus exacerbating hyponatraemic symptoms.
58
Give a potential cause of SiADH
One potential cause of SIADH is a paraneoplastic syndrome – for example, ectopic ADH secretion from a small cell lung carcinoma. Treatment primarily includes fluid restriction.
59
Sx of DI
This form of diabetes also involves the classic presentation of polyuria (increased frequency of urination), and subsequent polydipsia (excessive thirst)
60
Cause of DI
It can be due to either insufficient ADH release from the posterior pituitary gland (central diabetes insipidus), or the collecting ducts not responding to ADH (nephrogenic diabetes insipidus). If the actions of ADH are ineffective, less water will be reabsorbed from the filtrate. This means there will be a greater volume of filtrate, hence producing a greater volume of urine, causing the polyuria and polydipsia
61
What test can be used to cofirm DI?
A water deprivation test can be used as a confirmatory test for diabetes ins, after ruling out other common causes of polydipsia, such as hypercalcaemia.
62
Mx of DI
Management depends on the cause; in central DI, desmopressin (synthetic ADH) can be used whilst thiazide diuretics are used in the treatment of nephrogenic DI.
63
Main way sodium can enter principle cells from the lumen?
ENaC
64
Channel mainly responsible for reabsorption of potassium from the lumen into the cell in the DCT?
H+-K+-ATPase
65
Two ions excreted forms of hydrogen ion by intercalated cells?
Hydrogen phosphate and ammonium [NH4+]
66
Components of the glomerulus
- Endothelial cells of glomerular capillaries
- Glomerular basement membrane
- Epithelial cells of Bowman’s Capsule (podocytes
67
Describe structure of the endothelial cells
The glomerular capillary endothelium has many perforations called fenestrae, which are pores about 70nm in diameter. These pores actually do not restrict the movement of water and proteins or large molecules but instead prevent the filtration of blood cells (e.g. RBCs).
Surrounding the luminal surface of the endothelial cells is a glycocalyx consisting of negatively charged glycosaminoglycans. This functions to hinder the diffusion of negatively charged molecules by repelling them due to like charges.
68
Describe structure of the glomerular BM
The basement membrane surrounds the capillary endothelium and is mostly made up of type IV collagen, heparan sulfate proteoglycans and laminin. In particular, heparan sulfate proteoglycans help restrict the movement of negatively charged molecules across the basement membrane.
69
Layers of the BM
The basement membrane consists of 3 layers:
An inner thin layer (lamina rara interna)
A thick layer (lamina densa)
An outer dense layer (lamina rara externa)
These layers help to limit the filtration of intermediate and large sized solutes.
70
Describe the structure of epithelial cells
Podocytes are specialised epithelial cells of Bowman’s capsule which form the visceral layer of the capsule.
Foot-like processes project from these podocytes and interdigitate to form filtration slits. These filtration slits are bridged by a thin diaphragm (the slit diaphragm) which has very small pores. The pores prevent large molecules, such as proteins, from crossing. Similar to the endothelial cell glycocalyx, negatively charged glycoproteins cover the podocytes, restricting filtration of large anions.
71
What is ultrafiltration?
In the glomerulus, blood filters into the Bowman’s capsule in a process called ultrafiltration. Ultrafiltration is simply filtration that occurs under pressure. In this case, the afferent and efferent arterioles are responsible for generating pressure. The afferent arteriole (at the proximal glomerulus) dilates, while the efferent arteriole (at the distal glomerulus) constricts. This creates a pressure gradient throughout the glomerulus, causing filtration under pressure.
72
What is the filtration rate of molecules determined by?
The filtration rate of molecules of the same charge across the filtration barrier is inversely related to their molecular weight. Small molecules like glucose (180 Da) are freely filtered whereas albumin (69 kDa) is barely able to cross the barrier. The electrical charges on molecules also play a role in affecting their filtration rate. Negatively charged large molecules filter less easily than positively charged ones of the same size.
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Triad of nephrotic syndrome
Nephrotic syndrome is a triad of symptoms: proteinuria, hypoalbuminemia and oedema.
74
How common is minimal change disease as a cause for nephrotic syndrome?
Minimal change disease is responsible for 10%-25% of cases of nephrotic syndrome. In minimal change disease, glomeruli appear normal under a light microscope but pathology of the podocytes can be detected under an electron microscope. There is diffuse effacement of the podocytic foot processes, causing widening of filtration slits and visible microvillous changes
75
Simple PP of nephrotic syndrome
The pathology is still unclear and considered idiopathic. However, it is thought to be due to a T-cell-derived factor. Most patients respond well to steroids but, symptoms may relapse if they come off steroid therapy. Some patients become steroid dependant but most do not progress to chronic renal failure: those that do usually have focal segmental glomerulosclerosis as well.
76
Type of inheritance is Alport syndrome?
| [bonus: principle part of kidney affected]
Alport Syndrome is a X-linked genetic disease, which causes mutations of the gene coding for α-5 chain of type IV collagen.
77
Simple PP of Alport syndrome and presentation
It presents as progressive chronic kidney disease with haematuria, sensorineural deafness and ocular abnormalities. This results in thinning of the lamina densa in the glomerular basement membrane, with areas of multi-layering producing a basket-weave appearance.
78
Later stages of the disease and Tx for it
In later stages of the disease, glomerulosclerosis, interstitial fibrosis and tubular atrophy occur. There is no curative treatment for Alport syndrome. However ACE inhibitors can reduce progression of renal disease and proteinuria, as well as to control hypertension.
79
How is the structure of the PCT specalised for reabsorption?
The proximal convoluted tubule (PCT) has a high capacity for reabsorption, hence it has specialised features to aid with this. It is lined with simple cuboidal epithelial cells which have a brush border to increase surface area on the apical side. The epithelial cells have large amounts of mitochondria present to support the processes involved in transporting ions and substances.
Moreover, they also have a large number of channels on both the apical and basolateral membrane which provides a large surface area for transport of ions and other substances to occur
80
Main parts of the PCT
The proximal tubule can be divided into pars convolute and pars recta. The pars convolute resides in the renal cortex and it can further be divided into 2 segments; S1 (segment 1) and the proximal part of S2. The pars recta is a straight segment present in the outer medulla. It makes up the distal part of S2 and S3
81
Reabsorption function of the PCT
A large amount of reabsorption occurs in the PCT. Reabsorption is when water and solutes within the PCT are transported into the bloodstream. In the PCT this process occurs via bulk transport. The solutes and water move from the PCT to the interstitium and then into peri-tubular capillaries. The reabsorption in the proximal tubule is isosmotic.
The proximal tubules reabsorb about 65% of water, sodium, potassium and chloride, 100% of glucose, 100% amino acids, and 85-90% of bicarbonate. This reabsorption occurs due to the presence of channels on the basolateral (facing the interstitium) and apical membranes (facing the tubular lumen).
There are two routes through which reabsorption can take place: paracellular and transcellular. The transcellular route is transporting solutes through a cell. The paracellular route is transporting solutes through the intercellular space.
The driving force for the reabsorption in the PCT is sodium. On the apical membrane, it is usually co-transported with solutes e.g. amino acids and glucose, or in later segments of the tubule with chloride ions. The S1 segment of the PCT is not permeable to urea and chloride ions, hence their concentration increases in S1 which creates a concentration gradient which can be utilised in the S2 and S3 segments. Additional sodium is transported via a counter-transport mechanism that reabsorbs sodium whilst secreting other ions, especially H+.
On the basolateral side of the PCT cells, the 3Na-2K-ATPase pumps out intracellular Na+ ions. This transporter uses primary active transport. This movement of Na+ creates an electrochemical gradient favouring the movement of Na+ into the cell from the tubule lumen.
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How the pCT works as a co-transport
Co-transport refers to the movement of multiple solutes through the same channel.
The sodium concentration gradient allows other molecules, such as glucose, to be transported across the apical membrane against their concentration gradient. For example, SGLT transporters move glucose together with two sodium ions across the apical membrane. Glucose then crosses the basolateral membrane via facilitated diffusion.
Na+/Amino acid symporters are present on the apical side of cells in the S1 segment of the PCT which reabsorbs all the amino acids in the PCT.
Na+/H+ antiporter is another protein of the apical side of the cells in the PCT. It is an antiporter, and therefore transports ions across the cell membrane in opposite directions. In this case, the Na+ ions move into the tubular cells and the H+ is expelled into the tubule. The primary function of this transport it to maintain the pH.
83
How the PCT works to move water
In the PCT, large volumes of solute area transported into the bloodstream. This means that as we move along the tubule, the solute concentrations in the tubule are decreasing while the solute concentrations in the interstitium are increasing.
The difference in concentration gradient results in the water moving into the interstitium via osmosis. Water mainly takes the paracellular route to move out of the renal tubule but it can also take the transcellular route
84
Summarise the function of the PCT
image
85
Secretion from the PCT
Secretion is when substances are removed from the blood and transported into the PCT. This is very useful as only 20% of the blood is filtered in the glomerulus every minute, so this provides an alternative route for substances to enter the tubular lumen. The PCT secretes:
Organic acids and bases e.g. bile salts, oxalate and catecholamines (waste products of metabolism)
Hydrogen ions- important in maintaining acid/base balance in the body. H+ secretion allows reabsorption of bicarbonate via the use of the enzyme carbonic anhydrase (Fig 2). The net result is for every one molecule of H+ secreted, one molecule of bicarbonate and Na+ is reabsorbed into the blood stream. As the H+ is consumed in the reaction in the tubular lumen, there is no net excretion of H+. In this way, about 85% of filtered bicarbonate is reabsorbed in the PCT (the rest is reabsorbed by the intercalated cells at the DCT/CD later on)..
Drugs/toxins: Secretion of organic cations such as dopamine or morphine occurs via the H+/OC+ exchanger on the apical side of the tubule cell, which is driven by the Na+/H+ antiporter
86
Most common primary renal malignancy whcih originates form the PCT? [bonus: mutation, onset, RF, presentation]
Renal cell carcinoma (RCC) is the most common primary renal malignancy which originates from the PCT. It has been related to alterations in chromosome 3 which can non-hereditary or hereditary. Most commonly it occurs in men between the ages of 50-70.
Incidence of renal cell carcinoma has been linked with smoking and obesity. It can present clinically with haematuria, flank pain, fever and weight loss. It can invade in to the renal vein and then into the inferior vena cava. From here, it can metastasize hematogenously to lung and bones. RCC can also have paraneoplastic effects. In RCC paraneoplastic effects are caused by release of ACTH or PTHrP
87
What can acute tubular necrosis be caused by?
ATN can be caused by ischaemia which is usually occurs secondary to reduced renal blood flow (for example hypotension or sepsis). It can also be caused by nephrotoxic agents such as aminoglycosides and myoglobin. The ischaemia and toxins results in the death of tubular cells particularly the cells of the PCT.
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The ion chanels that can be affected by ATN
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89
What are SGLT2 inhibitors and how do they work?
Known as ‘gliflozins’ these are relatively new drugs used in the treatment of type 2 diabetes, however recent studies have shown benefit in non-diabetic cardiovascular disease and progression of CKD as well. Inhibition of the SGLT2 transporter leads to glucose being excreted, lowering blood glucose levels and contributing to some weight loss. Side effects include frequent UTIs, fungal infections and reported ‘euglycaemic diabetic ketoacidosis’.
90
Configuration of the Loop of Henle
Ion transport along the nephron is essential for the reabsorption of sodium and water, maintenance of plasma volume and blood pressure and production of urine. The Loop of Henle contributes to the absorption of approximately 25% of filtered sodium and can be targeted by diuretic therapy.
The Loop of Henle has a hairpin configuration with a thin descending limb and both a thin and thick ascending limb. The thin descending and ascending segments have thin epithelial membranes with no brush borders and minimal metabolic activit
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Function of the thick ascending limb in the Loop of Henle
The primary site of sodium reabsorption in the Loop of Henle is the thick ascending limb (TAL). The TAL is impermeable to water. Sodium (Na+ ) reabsorption is active- the driver is the Na+/K+ ATPase on the basolateral membrane which actively pumps three Na+ ions out the cell into the interstitium and two potassium(K+) ions into the cell. By creating a low intracellular concentration of sodium, the inside of the cell becomes negatively charged, creating an electrochemical gradient.
Sodium then moves into the cell (from the tubular lumen) down the electrical and chemical gradient, through the NKCC2 transporter on the apical membrane This transporter moves one Na+ ion, one K+ ion and two Cl– ions across the apical membrane. .
Potassium ions are transported back into the tubule by ROMK channels on the apical membrane to prevent toxic build up within the cell. Chloride ions are transported into the tissue fluid via CIC-KB channels.
The overall effects of this process are:
Removal of Na+ whilst retaining water in the tubules – this leads to a hypotonic solution arriving at the DCT.
Pumping Na+ into the interstitial space contributes to a hyperosmotic environment in the kidney medulla (see below)
There is also significant paracellular reabsorption of magnesium, calcium, sodium and potassium.
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Function of the thin ascneding limb in the Loop of Henle
Sodium reabsorption in the thin ascending limb is passive. It occurs paracellularly due to the difference in osmolarity between the tubule and the interstitium.
As the thick ascending limb is impermeable to water, the interstitium becomes concentrated with ions, increasing the osmolarity. This drives water reabsorption from the descending limb as water moves from areas of low osmolarity to areas of high osmolarity. This system is known as counter-current multiplication.
93
Function of the thin descending limb
The descending limb is highly permeable to water, with reabsorption occurring passively via AQP1 channels. Very low amounts of urea, Na+ and other ions are also reabsorbed. . As mentioned above, water reabsorption is driven by the counter-current multiplier system set up by the active reabsorption of sodium in the TAL.
94
Summarise the ion and water reabsorption within the Loop of Henle
image
95
What is bartter syndrome?
Bartter syndrome is a group of autosomal recessive conditions caused by genetic mutations in the genes that code for the NKCC2 transporter, apical potassium channel or basolateral chloride ion channel. The consequences are biochemically similar to administration of loop diuretics (see below). It results in hyponatraemia, hypokalaemia and metabolic alkalosi
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How do loop diuretics work?
Loop diuretics such as furosemide inhibit the NKCC2 transporter in the thick ascending limb. Loss of sodium reabsorption reduces the hypertonicity of the renal medulla, which impairs water reabsorption in the DCT and CD. This leads to increased excretion of sodium in the urine and significant diuresis, reducing plasma volume. By increasing sodium delivery to the DCT, there is increased potassium excretion. This is the mechanism behind the hypokalaemia frequently observed with loop diuretics.
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Where are chloride ions reabsorbed the most?
S2 and S3 of the PCT
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How is sodium reabsorbed in the thin ascneding limb?
Passively via paracellular routes
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How is sodium reabsorbed in the thick ascending limb?
Through the NKCC2 transporter
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What is excreted large amounts due to Furosemide?
water, sodium, cholride ion yes, glucose no
101
What is glomerulonephritis?
Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name,[1] but not all diseases necessarily have an inflammatory component.
Not strictly single disease and presentation depends on specific disease entity; may present wiht isolated haematuria and /or proteinuria, or as nephrotic syndrome, nepthritic syndrome, AKI, CKD
102
What is hydronephrosis?
[bonus: cause]
Hydronephrosis describes hydrostatic dilation of the renal pelvis and calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dilation of the entire upper urinary tract (both the renal pelvicalyceal system and the ureter).
The most common causes of hydronephrosis in children are anatomical abnormalities. These include vesicoureteral reflux, urethral stricture, and stenosis. The most common cause of hydronephrosis in young adults is kidney stones, or renal calculi. In older adults, the most common cause of hydronephrosis is benign prostate hyperplasia (BPH), or intrapelvic neoplasms such as prostate cancer. [4]
Compression of one or both ureters can also be caused by other developmental defects not completely occurring during the fetal stage such as an abnormally placed vein, artery, or tumor. Bilateral compression of the ureters can occur during pregnancy due to enlargement of the uterus. Changes in hormone levels during this time may also affect the muscle contractions of the bladder, further complicating this condition.
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What is kidney stone disease?
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is when a solid piece of material (kidney stone) develops in the urinary tract.[2] Kidney stones typically form in the kidney and leave the body in the urine stream.[2] A small stone may pass without causing symptoms.[2] If a stone grows to more than 5 millimeters (0.2 in), it can cause blockage of the ureter, resulting in severe pain in the lower back or abdomen.[2][7] A stone may also result in blood in the urine, vomiting, or painful urination.[2] About half of people who have had a kidney stone will have another within ten years.
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prevention/Tx kidney stones
Drinking fluids such that more than two liters of urine are produced per day.
If not effective, thiazide diuretic, citrate, allopurinal may be taken
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How common are kidney stones?
between 1-15% people globally affected by kidney stones some point in their lives
106
Define kidney failure [bonus; Sx and Cx]
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys are functioning at less than 15% of normal levels.[2] Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible.[6] Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion.[2] Complications of acute and chronic failure include uremia, high blood potassium, and volume overload.[3] Complications of chronic failure also include heart disease, high blood pressure, and anemia.
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What is nephrotic syndrome? [bonus: causes/Dx]
Nephrotic syndrome is a collection of symptoms due to kidney damage.[1] This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling.[1] Other symptoms may include weight gain, feeling tired, and foamy urine.[1] Complications may include blood clots, infections, and high blood pressure.[1]
Causes include a number of kidney diseases such as focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease.[1][2] It may also occur as a complication of diabetes or lupus.[1] The underlying mechanism typically involves damage to the glomeruli of the kidney.[1] Diagnosis is typically based on urine testing and sometimes a kidney biopsy.[1] It differs from nephritic syndrome in that there are no red blood cells in the urine
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What is minimal change disease?
Minimal change disease (also known as MCD, minimal change glomerulopathy, and nil disease, among others) is a disease affecting the kidneys which causes a nephrotic syndrome.[1] Nephrotic syndrome leads to the loss of significant amounts of protein in the urine, which causes the widespread edema (soft tissue swelling) and impaired kidney function commonly experienced by those affected by the disease.[1] It is most common in children and has a peak incidence at 2 to 6 years of age.[2] MCD is responsible for 10-25% of nephrotic syndrome cases in adults.[3] It is also the most common cause of nephrotic syndrome of unclear cause (idiopathic) in children.
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What is WIlm's tumour?
[bonus: Sx]
Wilms' tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children, rarely in adults.[1] It is named after Max Wilms, the German surgeon (1867–1918) who first described it,
Approximately 650 cases are diagnosed in the U.S. annually.[3] The majority of cases occur in children with no associated genetic syndromes; however, a minority of children with Wilms' tumor have a congenital abnormality.[3] It is highly responsive to treatment, with about 9/10 children being cured.
Typical signs and symptoms of Wilms' tumor include the following:
```
a painless, palpable abdominal mass
loss of appetite
abdominal pain
fever
nausea and vomiting
blood in the urine (in about 20% of cases)
high blood pressure in some cases (especially if synchronous or metachronous bilateral kidney involvement)
Rarely as varicocel
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What is renovascular hypertension?
Renovascular hypertension is a condition in which high blood pressure is caused by the kidneys' hormonal response to narrowing of the arteries supplying the kidneys.[1] When functioning properly this hormonal axis regulates blood pressure. Due to low local blood flow, the kidneys mistakenly increase blood pressure of the entire circulatory system. It is a form of secondary hypertension - a form of hypertension whose cause is identifiable
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What is PKD? [bonus: Sx, Tx, cause, Dx, Cx]
Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a genetic disorder in which the renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney.[5] These cysts may begin to develop in utero, in infancy, in childhood, or in adulthood.[6] Cysts are non-functioning tubules filled with fluid pumped into them, which range in size from microscopic to enormous, crushing adjacent normal tubules and eventually rendering them non-functional as well.
PKD is caused by abnormal genes that produce a specific abnormal protein; this protein has an adverse effect on tubule development. PKD is a general term for two types, each having their own pathology and genetic cause: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). The abnormal gene exists in all cells in the body; as a result, cysts may occur in the liver, seminal vesicles, and pancreas. This genetic defect can also cause aortic root aneurysms, and aneurysms in the circle of Willis cerebral arteries, which if they rupture, can cause a subarachnoid hemorrhage.
Diagnosis may be suspected from one, some, or all of the following: new onset flank pain or red urine; a positive family history; palpation of enlarged kidneys on physical exam; an incidental finding on abdominal sonogram; or an incidental finding of abnormal kidney function on routine lab work (BUN, serum creatinine, or eGFR). Definitive diagnosis is made by abdominal CT exam.
Complications include hypertension due to the activation of the renin–angiotensin–aldosterone system (RAAS), frequent cyst infections, urinary bleeding, and declining renal function. Hypertension is treated with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Infections are treated with antibiotics. Declining renal function is treated with renal replacement therapy (RRT): dialysis and/or transplantation. Management from the time of the suspected or definitive diagnosis is by a board-certified nephrologist.
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What is renal agenesis?
Renal agenesis is a medical condition in which one (unilateral) or both (bilateral) fetal kidneys fail to develop.
Unilateral and bilateral renal agenesis in humans, mice and zebra fish has been linked to mutations in the gene GREB1L.[1] It has also been associated with mutations in the genes RET or UPK3A.[2] in humans[3] and mice respectively.
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What is multicystic dysplastic kidney?
[bonus: Sx and Sx]
Multicystic dysplastic kidney (MCDK) is a condition that results from the malformation of the kidney during fetal development. The kidney consists of irregular cysts of varying sizes. Multicystic dysplastic kidney is a common type of renal cystic disease, and it is a cause of an abdominal mass in infants.
When a diagnosis of multicystic kidney is made in utero by ultrasound, the disease is found to be bilateral in many cases. Those with bilateral disease often have other severe deformities or polysystemic malformation syndromes.[6] In bilateral cases, the newborn has the classic characteristic of Potter's syndrome.[7][8]
The bilateral condition is incompatible with survival, as the contralateral system frequently is abnormal as well. Contralateral ureteropelvic junction obstruction is found in 3% to 12% of infants with multicystic kidney and contralateral vesicoureteral reflux is seen even more often, in 18% to 43% of infants. Because the high incidence of reflux, voiding cystourethrography usually has been considered advisable in all newborns with a multicystic kidney.
