Kidney Function 1

  • Created by: LBCW0502
  • Created on: 16-02-19 16:12
What are the functions of the kidney? (1)
Excretion of metabolites or ingested substances. Process plasma portion of the blood by removing substances in it (some cases adding substances). Generation of urine. Urea from protein catabolism. Uric acid from nucleic acid breakdown
1 of 67
What are the functions of the kidney? (2)
Creatinine from muscle creatinine. Hormone metabolites (e.g. growth hormone metabolites, insulin metabolites). Foreign chemicals (medicinal/non-medicinal, drugs, pesticides, food additives/metabolites). End products of Hb breakdown (yellow urine)
2 of 67
How does the kidney control body fluid composition? (1)
Directly controls composition of plasma (indirectly control composition of interstitial fluid/intracellular fluid). Volume regulation (directly linked to control of Na plasma concentration). Osmoregulation (water balance)
3 of 67
How does the kidney control body fluid composition? (2)
pH regulation (secretes H+, reabsorbs bicarbonate ions)
4 of 67
Which hormones act on the kidney?
ADH (vasopressin), aldosterone, natriuretic peptides, PTH, FGF23
5 of 67
Which hormones are produced by the kidney?
Renin, vitamin D3 (calcitriol), erythropoietin, prostaglandins, alpha-Kltho
6 of 67
Outline the gross structure of the kidney (1)
Two kidneys (one on either side of vertebral columns, situated between thoracic 12 vertebra and lumbar 3). Right kidney lower than left kidney to make way for the liver. Kidney size of a fist. Situated at back of abdominal cavity/outside peritoneum
7 of 67
Outline the gross structure of the kidney (2)
Each kidney has a convex surface (faces abdominal wall) and concave surface which faces each other. Concave surface has ureter which connects kidney to bladder. Urine passed via peristalsis through ureter to bladder (out through urethra)
8 of 67
Outline the gross structure of the kidney (3)
Kidney has two distinct tissue regions - outer cortex region and inner medulla region
9 of 67
Outline the basic unit of the kidney
Nephron (each kidney has over 1 million nephrons. Consists of initial filtering component (renal corpuscle) with a thin-walled, hollowed tube extending from this (tubule). Compact/folded appearance
10 of 67
Describe features of the renal corpuscle (1)
Two components. Glomerulus (capillaries) - compact interconnected capillary loops supplied with blood from afferent arteriole. Blood leaves via efferent arteriole. Bowman's capsule (analogy - fluid filled balloon punched with fist)
11 of 67
Describe features of the renal corpuscle (2)
Fluid filled - two sides of the Bowman's capsule do not meet/separated by Bowman's space. 20% of plasma entering glomerulus is filtered into Bowman's space across filtration interface
12 of 67
Describe features of the filtration interface (1)
Composed of 3 layers. Walls of capillaries (composed of endothelial cells) - fenestrated/highly permeable, pore size of <~15 nm, highly leaky (compared to skeletal capillaries of 5 nm and brain capillaries of 1 nm)
13 of 67
Describe features of the filtration interface (2)
Endothelial cells rest on basement membrane (basal laminar). Sites of fixed negative charges (polyanions). Walls of Bowman's capsule (composed of epithelial cells - highly specialised/podocytes - filtration slits with diameter of 8 nm)
14 of 67
Describe features of the filtration interface (3)
Direction of fluid movement across filtration interface - from lumen of glomerular capillaries to fluid filled Bowman's space
15 of 67
Describe features of podocytes
Cells have central cell body with long processes extending from it (pedicels - interlock but don't touch). Between pedicels are filtration slit proteins (nephrin and podocin)
16 of 67
The tubule is divided into which 8 distinct segments? (1)
PCT, proximal straight tubule, descending thin limb of Henle's loop, ascending thin limb of Henle's loop, thick ascending limb of Henle's loop, DCT, cortical collecting duct, medullary collecting duct
17 of 67
The tubule is divided into which 8 distinct segments? (2)
Urine drains from collecting duct into central cavity of the kidney (renal pelvis - goes through ureter to bladder for storage)
18 of 67
What are the two distinct nephron types?
85% - cortical type (renal corpuscle located in outer 2/3 of cortex, short loop of Henle. 15% - juxtamedullary (renal corpuscle located in inner 1/3 of cortex, long loop of Henle, produce concentrated urine)
19 of 67
Why does filtration only occur in the cortex?
This is where the renal corpuscle is located (responsible for filtration)
20 of 67
Describe features of the juxtaglomerular apparatus (1)
Composed of 3 cell types. Macula densa cells (located in wall of ascending limb of loop of Henle just as it turns into DCT). They directly oppose cells in walls of afferent arteriole (juxtaglomerular cells)
21 of 67
Describe features of the juxtaglomerular apparatus (2)
In-between maculae densa/juxtaglomerular cells are the extraglomerular mesangial cells (extra - outside glomerulus).
22 of 67
How many sets of capillary beds are there in the nephron?
2 - glomeruli (in glomerulus) and peritubular (close to tubule). Vasa recta (capillaries close to loop of Henle)
23 of 67
What are the basic renal processes?
Glomerular filtration, tubular reabsorption and tubular secretion
24 of 67
Describe features of glomerular filtration (1)
The movement of fluid and solutes from glomerular capillaries into Bowman's space. 20% of plasma that enters glomerulus if filtered (80%- passes into efferent arteriole). Initial filtrate in Bowman's space (start of urine formation/ultrafiltrate
25 of 67
Describe features of glomerular filtration (2)
Passive process which relies on local hydrostatic/osmotic pressure gradients. Filtration is a non-selective process (body eliminates substances from the blood without having a specific protein expressed for this)
26 of 67
Describe features of tubular secretion (1)
Secretion of solutes from peritubular capillaries into lumen of tubules. Movement of molecules from within walls of epithelial cells in tubule into lumen of tubule
27 of 67
Describe features of tubular secretion (2)
Secretion occurs predominantly in PCT but also occurs in collecting ducts
28 of 67
Describe features of tubular reabsorption
Movement of materials from filtrate in tubules into peritubular capillaries. Reabsorption can occur throughout whole of tubule
29 of 67
The amount of excreted urine is equal to what?
Amount filtered + amount secreted - amount reabsorbed
30 of 67
How is para-aminohippuric acid handled in the kidney?
Filtered and secreted but not reabsorbed (20% enters Bowman's space). Molecule is excreted in urine. Complete elimination from the blood through a single pass in the kidney (rare)
31 of 67
How is water and electrolytes handled in the kidney?
Filtered and some is reabsorbed. Some are passed into urine
32 of 67
How are glucose and bicarbonates handled in the kidney?
Freely filtered with complete reabsorption (not normally present in urine)
33 of 67
Give an example of a substance which is eliminated by the body via renal metabolism (in tubules)
Glutamine
34 of 67
Which molecules are found in the plasma but not in the filtrate?
Proteins - filtrate depends on molecular size/shape/charge
35 of 67
Outline features of molecular size and filtration
Molecular mass of <700 Da (same concentration in plasma and filtrate e.g. glucose and inulin with ratio of 1.0). Larger proteins (myoglobin - partially filtered, ratio of < 1.0). Albumin (completely excluded from filtrate)
36 of 67
Outline features of molecular charge and filtration
Large positively charged molecules have a greater ability to reach filtrate compared to uncharged or anionic molecule. Due to basement membrane having sites of fixed polyanions (attraction of + charged molecules, repel - charged molecules)
37 of 67
Describe features of the ultrafiltrate composition (1)
Similar composition to plasma but some differences in concentrations of some molecules e.g. proteins and molecules binding to proteins e.g. Ca 2+ (prevented from being freely filtered, 40% of Ca 2+ bound to proteins)
38 of 67
Describe features of the ultrafiltrate composition (2)
Drugs also bind to proteins/prevented being being freely filtered. Albumin binds acidic drugs but alpha 1-acid glycoprotein binds basic drugs
39 of 67
Infection, damage to glomerulus and very high BP can result in what?
Protein in urine (proteinurica). Hb in urine (haemoglobinuria). RBCs in urine (haematuria)
40 of 67
What is GFR?
Volume of fluid filtered from glomeruli per minute (mL/min)
41 of 67
GFR depends on a combination of what?
Starling forces (hydrostatic/osmotic pressure), SA of filtration interface (which is changeable) and hydraulic permeability of capillaries (leaky/fenestrated) - regulated by neural and hormonal input
42 of 67
Describe features of Starling forces (opposing) (1)
Hydrostatic pressures (60 mmHg - 15 mmHg) and colloid osmotic/oncotic pressure (29 mmHg - 0 mmHg. Fluid moves from lumen to capsular space. Ultrafiltrate has less (or no) proteins than in plasma. Few proteins (considered as 0)
43 of 67
Describe features of Starling forces (opposing) (2)
Net glomerular filtration pressure = (60-15) - (29-0) = 16 mmHg (fluid moves from capillary lumen to capsular space)
44 of 67
How can we control glomerular filtration rate? (1)
Restrict or dilate afferent arteriole. E.g. afferent arteriole constriction - reduced flow into glomerulus, reduced hydrostatic pressure gradient, reduce GFR. Efferent arteriole constriction - increase hydrostatic pressure, increase GFR
45 of 67
How can we control glomerular filtration rate? (2)
Dilate efferent arteriole - reduced hydrostatic pressure gradient, reduce GFR. Dilate afferent arteriole - increase hydrostatic pressure, increase GFR
46 of 67
How do we change the SA of filtration interface to change GFR?
Glomerular mesangial cells (found over glomerular capillaries within glomerulus). Contain smooth muscle actin, innervated by sympathetic NS (when activated, smooth muscle contracts, reduces SA for filtration)
47 of 67
What is the value for GFR?
125 mL/min of filtrate formed (180 L/day). Much higher than 4 L/day across all other capillaries in body (leaky). Urine output ~ 1.5 L/day due to reabsorption occurring
48 of 67
Where does reabsorption predominantly occur?
In the PCT and proximal straight tubule
49 of 67
Outline the structure of the tubule wall
Tubular lumen. Wall composed of single layer of epithelial cells. Peritubular capillaries close to wall. Luminal membrane of tubule cells faces filtrate. Basolateral membrane faces peritubular capillary
50 of 67
Describe features of the structure of the proximal tubule (1)
Walls are a single layer of columnar cells. Only segment which has brush border luminar membrane with numerous microvilli (increased SA for exchange to occur)
51 of 67
Describe features of the structure of the proximal tubule (2)
Densely packed with mitochondria (generate ATP - required by transporters e.g. primary/secondary active transporters, direct/indirect provided by ATP hydrolysis to ADP)
52 of 67
What is required for the proximal reabsorption of organic nutrients e.g. glucose and amino acids?
Na+ coupled co-transpoter (secondary active symporter expressed on lumen of epithelial cells). Tubular maximum system. Specific transporters for glucose and amino acids
53 of 67
Describe features of glucose reabsorption (1)
Filtered glucose normally reabsorbed. SGLT-Na+ dependent glucose co-transporter (Na moves from filtrate into cell down conc. gradient, provides energy for glucose to move from filtrate into cell against conc. gradient, transporter is saturable/Tm)
54 of 67
Describe features of glucose reabsorption (2)
Na in cell has low conc. compared to outside of cell due to activity of Na-K ATPase pump (in basolateral membrane, moves Na out of cell into EC fluid against conc. gradient and moves K against conc. gradient into cell)
55 of 67
Describe features of glucose reabsorption (3)
Na-K ATPase maintains low Na inside cell. Glucose inside cell and moves into EC fluid via facilitated diffusion (in basolateral membrane) using GLUT
56 of 67
Describe features of renal handling of plasma glucose (graph) (1)
Filtered load linearly proportional to plasma concentration. Filtered load matches reabsorption below plasma concentrations of 200 mg/dL = 11 mM. Plasma glucose doesn't rise above 150 mg/dL even after a sugary meal
57 of 67
Describe features of renal handling of plasma glucose (graph) (2)
Reabsorbed line shows variation with plasma glucose conc. Excreted = filtered - reabsorbed. Shows renal threshold of 200 mg/dL due to transport saturation (SGLT)
58 of 67
Describe features of amino acids (1)
Reabsorbed PT. At least 8 amino acid transporters (transport similar structures e.g. +/- charged, neutral amino acids). Overlapping amino acid specificity. 6 Na+ dependent amino acid transported expressed in PCT
59 of 67
Describe features of amino acids (2)
Mutations in PT basic amino acid transporters can cause kidney cystine stones. Majority of filtered protein reabsorbed in PCT by endocytosis and degraded to amino acids
60 of 67
Describe features of amino acids (3)
Important for destruction/inactivation of small polypeptide hormones e.g. insulin and growth hormone
61 of 67
Summarise PCT reabsorption
Na+ coupled transporters for glucose, amino acids, phosphate and sulphate. Passive reabsorption of urea, chloride, potassium, calcium (movement down conc. gradient) and bicarbonate (relates to H+ secretion, important in acid-base balance)
62 of 67
Describe features of secretion in proximal tubule
Two stage process, involves luminal/basolateral membrane transporters. Transporters are broadly selective (transport organic acids/bases). Only means of excretion for some protein bound molecules
63 of 67
Give examples of organic acids which are secreted in proximal tubule
Endogenous molecules e.g. bile salts, fatty acids, prostaglandins (renal vessel tone). Drugs e.g. furosemide, penicillin, acetazolamide. Diagnostic agent e.g. para-aminohippuric acid
64 of 67
Describe features of organic anion secretion in proximal tubule
OA- enters in cell/exchanged with dicarboxylate. DC- accumulates in cells my metabolism and Na+ coupled co-transport. OA- enters tubule lumen via ATP dependent transporters (MRP2, MRP4, ABCG2 - breast cancer protein)
65 of 67
Give examples of organic bases which are secreted in proximal tubule
Endogenous molecules e.g. creatinine, dopamine, choline, guanidine, histamine, serotonin, adrenaline. Drugs e.g. atropine, cimetidine, morphine
66 of 67
Describe features of organic cation secretion in proximal tubule
Enter cell via facilitated OCT2 (on basolateral membrane). Enter tubule lumen via multidrug and toxin extrusion proteins (MATE1/2) - antiporter in exchange for H+ and/or OCTN. MATE2-K only found in kidney, MATE1 found in other barriers
67 of 67

Other cards in this set

Card 2

Front

What are the functions of the kidney? (2)

Back

Creatinine from muscle creatinine. Hormone metabolites (e.g. growth hormone metabolites, insulin metabolites). Foreign chemicals (medicinal/non-medicinal, drugs, pesticides, food additives/metabolites). End products of Hb breakdown (yellow urine)

Card 3

Front

How does the kidney control body fluid composition? (1)

Back

Preview of the front of card 3

Card 4

Front

How does the kidney control body fluid composition? (2)

Back

Preview of the front of card 4

Card 5

Front

Which hormones act on the kidney?

Back

Preview of the front of card 5
View more cards

Comments

No comments have yet been made

Similar Pharmacy resources:

See all Pharmacy resources »See all Filtration, secretion, re-absorption resources »