ANATOMY
Vein first then artery and then pelvic
Superior mesenteric just above renal vein
Left gonadal vein drains there...so renal ca can cause left testicular varicoele
And can even extend to the left atrium
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●The kidneys are paired organs, 11–14 cm in length in adults, 5–6 cm in width and 3–4 cm in depth.
●They lie in the retroperitoneum, on either side of the vertebral column at the level of T12–L3 (the right kidney lies lower than the left, pushed down by the liver)
●Posteriorly — the diaphragm (separating pleura), quadratus lumborum, psoas, transversus abdominis, the 12th rib and three nerves—the subcostal (T12), iliohypogastric and ilio-inguinal (L1).Be careful during surgery as these three nerves can be damaged
Approach posteriorily during surgeries
●Anteriorly— the right kidney is related to the liver, the 2nd part of the duodenum (which may be opened accidentally in performing a right nephrectomy), and the ascending colon. In front of the left kidney lie the stomach, the pancreas and its vessels, the spleen, and the descending colon. The suprarenals sit on each side as a cap on the kidney’s upper pole.
The kidney has, in fact, three capsules:
●Fascial (renal fascia)
●Fatty (perinephric fat)
●true — the fibrous capsule which strips readily from the normal kidney surface but adheres firmly to an organ that has been inflamed.
Kidney therefore moves with respiration as attached to diaphragm
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Blood supply
●The renal artery derives directly from the aorta.
●The renal vein drains directly into the inferior vena cava.
●The left renal vein passes in front of the aorta immediately below the origin of the superior mesenteric artery.
●The right renal artery passes behind the inferior vena cava.Lymph drainage
●Lymphatics drain directly to the para-aortic lymph nodes.
-----------------------------Nerve supply
●The renal capsule and ureters are innervated via T10–12 and L1 nerve roots, and renal pain is felt over the corresponding dermatomes.
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Embryology
Embryological variations
As the kidney ascends from the pelvic into the abdominal cavity it derives blood supply from different sources
And sometimes canget stuck and recieve blood supply from that
And other anatomical varation
Complete list of all anatomical variations of the kidney?
Course of the ureter
ureters are running along the transverse process of l2 to l5 vertebrae
and then in front of the ischial spine and then turns forward and joins the bladder
Relation to ureterine arteries? can by mistakely cut the ureter during hysterectomy! and need repair.....
three constrictions of the ureter
1 where pelvis joins the uereter
2 pelvic brim
3. ueretic orifice - when the uereter enters the bladder
stones are most likely to be lodged here
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XRAY - KUB
Where to look for the stones - transverse process of l2 to l5 and then ischial spine and then entered bladder - junction
90% of the time they are radio opaque - not transparent
vs 10% of the time in cholelithiasis
HISTOLOGY >>>>>
HISTOLOGY
●Each kidney is enclosed in a fibrous capsule, and has an outer cortex and an inner medulla
●There are about 1 million nephrons in each kidney.
●Each nephron contains a glomerulus, proximal tubule, loop of Henle, distal tubule and collecting duct.
●All glomeruli lie in the cortex, and tubules dip in and out of the medulla, where the collecting ducts merge to form the ducts of Bellini, emptying at a papilla at the apex of renal pyramid into a calyx.
●Urine then flows through merging calyces into the renal pelvis, ureters and bladder.
●The renal arteries branch off the abdominal aorta, dividing into smaller branches until arterial blood reaches the glomerulus.
●About 25% of people have dual or multiple renal arteries on one or both sides.
●Afferent glomerular arterioles arise from interlobular branch arteries to supply the glomerular capillary tuft, which drains into efferent glomerular arterioles
●Efferent arterioles from (outer) cortical glomeruli drain into a peritubular capillary network within the renal cortex and then into increasingly large and more proximal branches of the renal vein.
●By contrast, blood from the (inner) juxtamedullary glomeruli passes via vasabrecta in the medulla and returns via the cortex to renal veins that drain into the inferior vena cava.
●A ball of capillaries makes up the glomerular tuft, enclosed by Bowman's capsule, a chamber lined with specialized parietal epithelial cells that marks the origin of the tubule
●The tuft, held together and regulated by mesangial cells, then serves as the filtration barrier, allowing filtrate from plasma to move into the urinary (Bowman's) space.
●The rate of glomerular filtration is influenced by changes in the contractile tone in either the afferent or the efferent arterioles; for example, efferent vasoconstriction will increase the transglomerular capillary pressure, and increase filtration.
●Glomerular capillaries are lined with endothelial cells, fenestrated with 60–80nm pores, and covered with charged glycocalyx.
●The glomerular basement membrane (GBM), about 300 nm thick and made of type IV collagen, laminin and heparin sulphate, separates endothelium from podocytes (or visceral epithelial cells).
●Podocytes anchor on to the GBM by means of an extensive trabecular network of foot processes, and hang into Bowman's space
●The interdigitating foot processes of podocytes then form the 40-nm filtration slit, a narrow potential space traversed by a protein ‘zipper’ that may prevent the passage of larger molecules (such as albumin) into the urinary space, and regulates the architecture and function of podocytes.
●Mesangial cells (thought to be related to macrophages) sit within the tuft, able to contract and relax to control blood flow and the filtration surface area along the glomerular capillaries in response to a host of mediators.
●They also secrete the mesangial matrix, which provides the scaffolding for glomerular capillaries.
●The renal tubules are lined by epithelial cells, which alter the composition of filtrate to form urine eventually.
●Proximal tubular cells have a luminal brush border to increase (by 30fold) the surface area exposed to filtrate, rich in transporters and channels.
●The loop of Henle is lined with squamous cells, which are more permeable to water than solute, and cuboidal epithelium, when the reverse is true.
●The distal tubule regulates electrolytes and pH through cuboidal epithelium, and the cortical portion of the collecting ducts contains two cell types with different functions: principal cells (sodium, potassium and water) and intercalated cells
●Finally, resident interstitial fibroblast-like cells in the renal cortex produce erythropoietin in response to hypoxia
--------------------------------Juxtaglomerular apparatus
●The distal end of the renal tubule passes next to the glomerulus to form juxtaglomerular apparatus (juxta means “next to”)
●The juxtaglomerular apparatus regulates flow and filtration in each individual nephron.
●Columnar epithelium in the macula densa senses the concentration of tubular fluid sodium (higher filtrate flow means more delivered sodium), triggering adenosine-mediated vasoconstriction of the afferent arteriole to drop glomerular filtration (so-called tubule–glomerular feedback).
●Juxtaglomerular cells secrete renin, able to induce aldosterone release allowing the apparatus to monitor flow, and respond when necessary to drop glomerular filtration rate (GFR) and retain salt to maintain fluid balance.
-----------------------------urethra anatomy??????
Urethral issues and ruptures???
Pathology full of the kidneys (some tutes)??
Will be covered in medicine as well!!!!!??????
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PHYSIOLOGY
IMPORTANT TO KNOW RENAL FOLURE OR NOT AS DOSAGES OF DRUGS NEED TO BE REDUCED. NEED TO KNOW WHICH DRUGS ARE EXCRETED BY THE KIDNEY AND HENCE NEED DOSE ADJUSTMENTS.
NEED BMF TO KNOW WHETHER NEED RENAL PRECAUTIONS FOR THAT DRUG OR NOT.
AND CHECK UP WHETHER NEED DOS ADJUSTMENTS
FUNCTIONS:
1.Excretory
1.Regulatory
1.Metabolic
1.Endocrine Excretions:
●Metabolic waste products - creatinine, urea, uric acid, urobilinogen
●Foreign chemicals - drugs and metabolites of drugs and various hormones and food additivesRegulatory -
●Control of body fluid volume and composition
- Regulation of water and electrolyte balances
- Regulation of body fluid osmolality and electrolyte concentrations
●Regulation of acid-base balance
●Regulationof arterial blood pressureMetabolic -
●Metabolism of vitamin D
●Metabolism of small molecular weight proteins ex: insulin, PTH, calcitonin
●GluconeogenesisEndocrine - production of ●Erythropoietin
●1,25 - DHCC
●Renin
●Prostaglandins
●Kinins
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Glomerular filtration
●Fluid transfers/filters from glomerular capillaries into Bowman's capsule
●Glomerular filtrate -
- Isotonic to plasma
- Water
- Glucose
- Waste products
- Electrolytes
- Free of protein, fat and blood cells
Glomerular filtration rate (GFR)
●An index of renal function
●125ml/min/1.73m2 in a healthy adult male
●This is the total rate of filtration by all glomeruli in both kidneys
●In health GFR depends on
- Age - elderly people have lower GFR
- Gender - in female 10% less compared to male
- Body surface areaFactors that determine GFR
1.Net filtration pressure
- Hydrostatic pressure
- Osmotic pressure
1.Glomerular ultrafiltration coefficient - Kf
- Surface area of filtration
- Permeability of membrane
- More permeable than the other membranes
- Size and charge of molecules
●Changes in renal blood flow
●Glomerular Hydrostatic pressure
- Mean arterial blood pressure
- Afferent and efferent arteriolar constriction
●Hydrostatic pressure in Bowman's capsule
- Obstruction in the ureters
- Edema of the kidney inside tight kidney capsule
●Glomerular Osmotic pressure
- Changes in plasma protein concentration
●Kf
- Changes in membrane permeability and surface areaRenal clearance
●The volume of plasma that is completely cleared of the substance by the kidneys in unit time
●Amount of a substance (X) removed by the kidney in unit time
= Ux mg/ml * V ml/min
●Clearance of substance X (Cx) = Ux mg/ml * V ml/min
Px mg/mlZero clearance
●All the substance filtered is completely reabsorbed at PCT
●Clearance is zero
●Concentration in renal artery = renal vein
Ex: Glucose Complete clearance
●Almost completely removed in a single circulation
●By filtration and tubular secretion
Ex: Para-aminohippuric acid (PAH)
Partial clearance
●By filtration and tubular secretion
Ex: Creatinine
●The concept of ‘clearance’ can be used to measure GFR and RBF
Serum creatinine level as a measure of renal function
●Glomerular filtration is the main process responsible for excretion of creatinine
●When GFR is reduced, theoretically there should be an increase n serum creatinine levels
●Serum creatinine is used more often than creatinine clearance
●Relationship between serum creatinine and GFR is not linear
important!!
Urea
●Urea is another waste product that can be used to assess GFR
●Urea excretion - 95% by the kidney
●Serum urea is influenced by many factors
●Increased urea levels
- High protein diet
- High protein catabolism
- Dehydration
- Bleeding into the GIT
●Reduced urea levels
- Low protein diet
- Liver failure
- Old agePAH clearance
●Applying ‘Fick principle’ we can determine the renal blood flow
●Renal blood flow = Rate of removal of PAH
Arterio-venous difference of PAH across the kidney
●Effective renal plasma flow = PAH clearanceRenal blood flow
Kidneys receive extremely high blood flow - 1200ml/min
●To supply nutrients
●To remove waste products
●To supply enough plasma for high rates of glomerular filtration
Autoregulation - Intrinsic renal mechanism
●Change of arterial pressure between 90 - 220 mmHg
●Renal vascular resistance varies
●Keeps RBF and GFR relatively constant RBF depends on MAP
●When the pressure is high,
AA constrict in response to stretch - contractile response of vascular smooth muscles to stretch - NO may play a role
●When the pressure is low,
EA constrict angiotensin llPhysiological control of GFR and RBF
●Autoregulation
- Tubuloglomerular feedback
- Myogenic contractions of vessels to stretch
- Glomerulotubular balance
●Reflex activation of sympathetic nervous system
- Renal vasoconstriction - reduced RBF and GFR
●
Hormones and autocoids
(autocoids are vasoactive substances released in the kidneys and act locally
Hormonal and autocoid control of renal circulation
●Noradrenaline and adrenaline - vasoconstriction
●Endothelin - vasoconstriction
Released from damaged vascular endothelial cells of the kidney
●Angiotensin ll more vasoconstriction on EA than AA
●Dopamine, endothelial derived NO - vasodilation
●Prostaglandins vasodilation
>>>>> TUBULAR FUNCTION NEXT CARD
Tubular functions
●Tubular reabsorption
●Tubular secretion
●Changes the composition of the filtrate
●Tubular reabsorption is highly selective
●Depending on the requirement of the body, kidney can regulate the excretion of solutes independently of one anoth
er
●Urinary excretion of a substance =
[Glomerular filtration - tubular reabsorption] + tubular secretion Transportation of water and solutes
●Transcellular route - through cell membrane themselves
●Paracellular route - through the junctional spaces between cells Transport systems in tubules
●Passive diffusion - between cells - water
●Facilitated diffusion - through cells down the chemical and electrical gradients - water, urea
●Active transport - Na+, glucose
●Endocytosis - small proteins and peptide hormones - in the PCT
>>> in the distal tubule chlroide chlrodie co transporter ....
>>> in the collecting ducts ENaC - epithelial sodium channels .
Glucose reabsorption
●Na+ dependent llry active transport (SGLT2)
●Completely reabsorbed at PCT
●Renal threshold for glucose - 200mg/dl [artery]
180mg/dl [vein]
●Tm for glucose - 375mg/min (male), 300mg/min (female)
Tm - Tubular maximum
Water excretion
●GFR 125ml/min = 180L/day
●Urine 1L/day
Water reabsorption
At the PCT,
●Passive diffusion of water occurs due to osmotic pressure difference in the tubular lumen and interstitial fluid
- Simple diffusion
- Water channels - aquaporin 1
- Na+ dependent
At the CD,
●Water reabsorption is independent of Na+ reabsorption
●ADH dependent - insertion of water channels (aquaporin 2)
●A healthy person should excrete 600/700 mosm of solutes each day in order to get rid of waste products of metabolism
●Maximum urine concentrating ability - 1200 mosm/L
●Minimum osmotic load that has to be excreted per day - 600 mosm/L
Obligatory urine volume = 600
1200
= 0.5 L
Water excretion
Kidneys regulate water excretion independently of solute excretion
●When there is excess water in the body,
Kidneys produce dilute urine by inhibiting ADH
●When there is a water deficit,
Kidneys produce concentrated urine by increasing levels of ADH
Requirements for forming concentrated urine
●Vasopressin or ADH
●Hyperosmolarity of the medullary interstitium - the mechanism responsible for this is “Countercurrent mechanism”
●Gradient of increasing osmolarity along the medullary pyramids
●Gradient is created and maintained by Countercurrent mechanism
●Low medullary blood flow minimizes the loss of solutes from the medullary interstitium
●Recirculation of urea in the medulla contributes to the medullary hyperosmolarity
Countercurrent mechanism
●Inflow runs parallel
Counter
Close proximity to outflow
●Countercurrent multiplier - LOH of juxtamedullary nephrons
●Countercurrent exchanger - Vasa recta
Role of urea
●About 20-50% of filtered urea is excreted
●Rate of urea excretion depends on
- [urea] in plasma
- GFR
●About 40-50% urea is reabsorbed passively by PCT
●Thick LOH, DCT and cortical CD are relatively impermeable to urea
●Permeability of medullary collecting ducts to urea is increased by ADH
●Recirculation of of urea contributes to hyperosmotic medullary interstitium
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Regulation of ECF osmolality and ECF volume
●Osmolality (total solute concentration in ECF) = Total solutes in ECF
Total body water
●280-296 mosm/kg of water
●Regulation of ECF osmolality and [Na+] are closely linked
●Volume = Total amount of osmotically active solutes in the ECF
(The amount of Na+ in the ECF)
Defence of the osmolality of the ECF ECF [Na+] and osmolality are regulated by the amount of water in the ECF
1.Thirst mechanism
1.Osmoreceptor - ADH (vasopressin) system
Factors that increase ‘Renin’ secretion
●Intra-renal baroreceptor mechanism - reduced pressure in AA
●Decreased delivery of Na+ and Cl- to the DCT - detected by ‘macula densa cells’
●Increased sympathetic stimulation via renal nerves
●Increased circulating catecholamines
●Prostaglandins - by a direct action on JG cells
●Inhibited by Angiotensin ll, ADH and ANP
Natriuretic hormones
- ANP (Atrial Natriuretic Peptide)
- BNP (Brain NP)
- CNP (C-type NP)
Actions
●Dilate AA
●Relax mesangial cells
●Inhibit Na+ reabsorption
●Increase capillary permeability. Decrease in blood pressure
Defenses against changes in H+ concentration
- Buffers in blood and intracellular proteins
- Respiratory contribution
- Renal contribution - Kidneys can excrete either acidic or basic urine
- HCO3- are filtered and reabsorbed
- New HCO3- are produced
- H+ are secreted and excreted
●H+ secretion > HCO3- reabsorption - Kidneys excrete acidic urine
●HCO3- excretion > H+ secretion - Kidneys excrete basic urine
Buffers in the tubules
●Bicarbonate buffer system - filtered HCO3-
Important role in PCT - 24 mEq/L
Minor role in late DCT and CD - concentration low
●Phosphate buffer system - filtered HPO42-
Minor role in PCT - 1.5 mEq/L
Important role in late DCT and CD - concentration high
●Ammonia buffer system - made in renal tubular cells
Factors that increase H+ secretion and HCO3- reabsorption by the renal tubules
●Increased pCO2
●Increased H+, reduced HCO3-
●Reduced ECF volume
●Increased Angiotensin ll
●Increased Aldosterone
●Hypokalemia
BLADDER >>>
BLADDER
PATHOLOGY
Crescentic (Rapidly progressive) GN
●Characterized by rapid and progressive loss of renal function associated with severe oliguria
●There is crescent formation in most glomeruli
●Crescents are formed by proliferation of parietal epithelial cells and infiltration by monocytes and macrophages
●Occurs in response to leakage of fibrin in to Bowman's space due to glomerular necrosis
REST OF PATH >>>>>
AKD
PHARMACOLOGY OF NEPHRO
QUESTIONS AND ANSWERS
1.Regarding the anatomy of the kidney
A.They are in the peritoneal cavity
B.The blood supply is derived from the coeliac axis
C.The hilum of the left kidney is lower than that of the right
D.The hilum of the left kidney is at the level of L1 spine
E.Can be surface marked anteriorly by the lumbar triangle
1.A. F - situated retroperitoneally
B. F - from the abdominal aorta
C. F - right lower than the left, due to presence of liver
D. T
E. F - lumbar triangle is formed by free Posterior border of external oblique, anterior border of latissimus dorsi and the iliac crest
02. Following are actively reabsorbed in the PCT
A.Chloride
B.HCO3-
C.Water
D.Na+
E.Glucose 02. A. F - mainly by diffusion in second half of PCT
B. F - passive diffusion with formation of H2CO3
C. F - 60-70% passively via Aquaporin 1 channels
D. T - 60% mainly actively via Na+/H+ exchanger
E. T - 100% actively via Na+/Glucose co-transporter
03. Regarding the filtrate of the PCT
A.It is formed by active transport
B.Na concentration is 140 mmol/l
C.Contains plasma protein
D.Is isotonic to plasma
E.Becomes progressively hypertonic as it goes towards the medulla
03. A. T
B. T
C. F - not filtered from glomerulus
D. T - with similar proportions of reabsorption of salt and water
E. T - due to hypertonic medullary interstitium and since descending limb of loop of Henle is permeable to water, but not to solutes
04. Which of the following is true
A.H+ ATPase - distal tubule
B.Na+/2Cl-/K+ transporter - ascending limb of loop of Henle
C.Na+/Cl- co-transporter - distal convoluted tubule
D.Na+/Glucose co-transporter - distal convoluted tubule
E.Epithelial Na+ channel - collecting duct
04. A. T - Na+/H+ exchanger in PCT
B. T - thick ascending limb. Reabsorbs 30% sodium
C. T - reabsorbs 7% sodium
D. F - PCT
E. T - reabsorbs 3% : regulated by Aldosterone
05. Regarding the minimal change disease
A.Is the commonest cause of adulthood nephrotic syndrome
B.Microscopy reveals widespread fusion of podocyte foot processes
C.Give rise to nephritic syndrome with normal renal sediments
D.Chronic kidney disease is a common sequelae
05. A. F - Childhood nephrotic. Adult nephrotic is mainly due to membranous nephropathy
B. F - light microscopy shows no change in glomeruli. Only electron microscopy shows this change
C. F - nephrotic syndrome with bland sediment (similarly FSGS, membranous types give bland sediments. Proliferative types give active sediments)
D. F - very rarely even in adults (less than 5%)