Block 10 Flashcards
(107 cards)
1
Q
Describe the process of events that occur in pre renal acute kidney injury.
A
Low blood supply to kidneys —> reduced GFR —> accumulation of H2O and solutes in the blood. If severe hypo perfusion, glomerular necrosis may occur.
= oligurea or anurea
Blood supply to the kidneys has to fall quite low before AKI due to necrosis becomes apparent (~20% of normal). This is because the majority of energy of renal cells is used for powering Na+ pump. As perfusion and GFR decreases, there is less need for the Na+ pumps and so the cells require less energy and O2 etc.
THIS IS THE MOST COMMON CAUSE OF AKI
2
Q
What is intra renal acute renal failure?
A
Failure of the flirtation function of the kidneys due to an abnormality within the kidney itself. The most common cause is glomerulonephritis (especially post streptococcal).
Other causes: acute tubular necrosis & acute interstitial nephritis
3
Q
Describe the pathophysiology of glomerulonephritis
A
Commonly a hypersensitivity reaction usually caused post infection with a streptococcal sore throat.
It is a type 3 reaction where antigen/antibody complexes precipitate into the micro vessels of organs, especially the kidney. They become trapped in the glomerular basement membrane and cause an inflammatory reaction.
LOTS of different causes and usually results in one or both or nephritic and nephrotic syndrome.
4
Q
What is the difficulty with acute post renal failure?
A
Depending on where the blockage is, it can present very late on where irreversible kidney damage has already occurred.
This is because a blockage of one kidney can be compensated for (in most part) by the other kidney, leaving very few, if any, symptoms. This is only the case in partial or one sided blockages however.
5
Q
What are the physiological effects of acute renal failure and how these occur.
A
Oedema and hypertension
Reduced GFR –> retention of Na+ and H2O
Arrhythmia
retention of K+ –> hyperkalaemia
Metabolic acidosis
retention of H+ –> acidosis –> respiratory compensation
(A patient will die within 7-14 days if no treatment is given!)
6
Q
What is the definition of of chronic renal failure?
A
A progressive and irreversible loss of functioning nephrons.
Unfortunately, there are no/few symptoms until the number of nephrons drops by ~70% as the remainder can hypertrophy and compensate
7
Q
What are some causes of chronic renal failure?
A
Metabolic disorders (diabetes)
Hypertension
Renal vascular disorders (stenosis and atherosclerosis)
Immunological (glomerulonephritis)
Infections
Urinary tract dysfunction (prostatic hyperplasia)
Congenital disorders (PKD)
8
Q
Describe the ‘vicious cycle’ in CKD.
A
Decrease in nephron number –> Increased arterial pressure –> increased glomerular pressure –> glomerular stenosis
Hypertrophy and vasodilation of the remaining nephrons can somewhat compensate the increased GFR and delay diseases progression.
9
Q
What is the method of decreasing the progression of CKD?
A
Only way is to lower arterial pressure and reduce the resultant pressure on the glomeruli. This is done though antihypertensive medication (A/B/C/D)
10
Q
What are the other functions of the kidney (other than filtration) that are impaired in CKD.
A
EPO production –> anaemia
Vit D synthesis –> osteomalacia
Renin secretion –> hypotension (probably not common as major cause of CKD is hypertension!)
11
Q
What are some common symptoms of kidney disease?
A
Hypertension
Loin pain
Kidney mass
Ureteral bleeding
Loss of excretory function (oligurea, frequency, hesitancy)
Loss of solute homeostasis (malaise, sweats, heavy breathing)
12
Q
Name some lower urinary tract symptoms.
A
Hesitancy Delay Straining Incomplete emptying Terminal dribbling Frequency Nocturea Urgency Incontinence Dysurea
13
Q
What are the visible features of urine to note?
A
Volume Colour Odour Cloudiness Consistency Frothiness Debris
14
Q
What are the common causes of polyurea?
A
Early CKD (loss of ability to concentrate) Osmotic diuresis (glucose in diabetes mellitus) Post-renal obstruction (very common) UTI
15
Q
What are the common causes of oligurea?
A
Acute Kidney Injury
16
Q
What are the common causes of anurea?
A
Complete post-renal obstruction
Severe renal failure
17
Q
What are some changes of colour in urine to note and their meanings?
A
Pale = dilute = excess water Dark = concentrated or bile pigments Pink = blood or beeturea Red = blood Brown/red = muscle breakdown
18
Q
What are the tests of a urine dipstick and their common meanings?
A
Leucocyte esterase = presence of white cells Nitrites = created from nitrates by bacteria Urobilinogen = haemolysis Protein = glomerular injury pH = high in bacterial infection/RTA Blood = damage to urinary system Specific gravity = dilute of excess ADH Ketones = ketoacidosis Bilirubin = Obstructive jaundice Glucose = Diabetes mellitus
19
Q
Advantages and disadvantages of screening an asymptomatic family member for PKD or any other inherited condition.
A
Advantages:
Aware of possible problems
Able to monitor and treat early
If female, can monitor effect in pregnancy
Disadvantages;
Employment difficulty
Insurance
Ethical issues about passing disease onto children.
20
Q
What are the advantages and disadvantages of dialysis?
A
Immediately life saving! Close intact with hospital MDT Bridge to transplantation Relief from isolation and loneliness? Opportunity for further social interaction
21
Q
Impact of dialysis on a patients life.
A
Not 100% effective so still have some level of kidney failure and accompanying symptoms
Takes up A LOT of time (travel, clinics, dialysis)
Limitation of travel
May make it hard to get out of the hose
Depression and other psychological illnesses are common
22
Q
What is GFR auto regulation?
A
A mechanism within the kidney to maintain a constant GFR.
low BP –> reduced GFR –> reduced solute in kidney –> detected by juxtaglomerular cells –> renin release –> RAAS –> angiotensin 2 causes efferent arteriole vasoconstriction
This increases the BP in the glomeruli (among many other things) which causes a resultant GFR
23
Q
What are the hormonal and neural influences which determine if Na+ is retained or lost?
A
Retaining: RAAS Renal nerve stimulation Noradrenaline ADH
Loosing: ANP Prostaglandins Bradykinin Dopamine
24
Q
What is the main change which causes vasopressin release?
A
An increase in blood osmolarity (measured by osmoreceptors in hypothalamus)
25
What are the consequences of basement membrane damage of the glomeruli (glomerulonephritis)?
Protein loss: (usually >3.5g/day)
Nephrotic syndrome = peripheral oedema, proteinurea, hypoalbuminaemia, hypercholesterolaemia
Blood loss:
Nephritic syndrome = haematurea, hypertension, AKI, oligurea, proteinurea, oedema (2˚ to oligurea)
26
What are the main causes of nephrotic syndrome in both adults and children?
```
Adults:
Membranous glomerulonephritis
IgA nephropathy
Diabetic nephropathy
SLE
Amyloidosis
```
Children:
Minimal change glomerulonephritis
Focal-segmental glomerulonephritis
27
What is sensitivity?
The number of people WITH the disease who will have a positive result.
No. of true positives / ALL those with disease
28
What is specificity?
The number of people WITHOUT the disease who will have a negative result.
No. of true negatives / ALL those without disease
29
What is positive predictive value?
No. of true positives / ALL those testing positive
30
What is negative predictive value?
No. of true negatives / ALL those testing negative
31
What happens to sensitivity, specificity, PPV and NPV as prevalence of the disease rises?
sensitivity and specificity remain constant
PPV value will RISE
NPV value will FALL
32
What can a test with a high sensitivity but a low specificity be used for?
Ruling out a disease.
A positive result may be a false positive , however, a negative result is very unlikely to be a false negative.
33
What can a test with a low sensitivity but a high specificity be used for?
Ruling IN a disease.
A negative result may be a false negative, but having a high specificity means that a positive result is very unlikely to be a false positive.
34
What are the signs and symptoms of nephritic syndrome?
Blood in the urine:
Haematurea
Proteinurea
Oligurea
Oedema (2˚ to oligurea)
35
What are the signs and symptoms of nephrotic syndrome?
Protein in the urine:
Proteinurea
Hypoalbuminaemia
Hypercholesterolaemia (reduction in lipoprotein lipase leads to reduced breakdown of LDL)
Oedema
36
What are the main classes of post-renal failure? Give some examples of each
Kidney:
prolapse, calculus, neoplasm, narcotising papillitis
Ureters:
stricture, stenosis, kinks, infection, valve, retrocaval, neoplasm, calculus, compression, peri-ureteral inflammation (appendicitis)
Bladder:
uterocele, neoplasm, calculus, foreign body
Urethra:
Neoplasm, stricture, stenosis, diverticulum
Prostate:
BPH, prostatitis, neoplasm, cyst
37
What are the symptoms of post-renal failure?
```
Abdo pain
Unrelenting full bladder
Frequency
Retention
Dysurea
Hesitancy
Slow flow
Recurrent UTIs
Intermittency
Nocturea
```
38
What are the 3 TYPES of obstruction that post-renal failure can be classified as?
MURAL (to do with the wall)
LUMINAL
EXTRA-MURAL
39
What are the two muscles of the bladder and their function?
Detrusor = major muscle of the bladder, rugaeted on inside, contracts to high pressure (~50mmHg)
MAIN MUSLCE OF MICTURITION
Trigone = forms triangle between ureters and urethra. A smooth muscle. Detects stretch of the bladder
40
What is the sympathetic innervation to the bladder?
L2 --> hypogastric plexus --> detrusor and trigone
Innervates blood vessels and mediates their contraction. Not to do with the muscles directly.
41
What are the two sphincters within the bladder?
Internal sphincter = functional sphincter within the elastic tissue of the bladder neck. Natural tone which prevents emptying until a certain pressure is reached.
External sphincter = muscle within the perineum under somatic control. Function to prevent micturition in the presence of autonomic impulses.
42
What and where are the sensory and motor fibres innervating the bladder?
S2-S4 --> pelvic nerves --> sacral plexus --> bladder
Sensory mainly comes from the trigone and strong impulses from the INTERNAL SPHINCTER
Skeletal motor fibres to the external sphincter to via the pudendal nerve.
43
What is the micturition reflex?
The autonomic reflex to cause micturition when the bladder becomes full.
These come in waves and get more frequent and stronger as the bladder gets fuller. If the bladder does not empty after one of these 'waves' then it dissipates again until the next one comes. (NERVES ARE INHIBITED)
Once the waves become too powerful they can override the central voluntary control of the external sphincter to cause urination.
44
What are the two different types of nephron and their differing blood supply?
Cortical nephrons = L of H defends slightly into the medulla, supplied from peritubular capillaries from radial arteries of the arcuate arteries. Drains into the stellate vain
Juxtamedullary nephrons = L of H is entirely in the kidney medulla. Supplied from vasa recta directly from the acriate artery, drains into the arcuate vein.
45
What are the main areas of a nephron?
```
Glomerulus
Bowman’s capsule
Proximal tubule
Loop of Henle
Macula densa
Distal tubule
Collecting duct
```
46
What is the histology of the proximal tubule?
Cuboidal epithelial cells
Rich in mitochondria (lots of re-absorption)
Brush border microvilli to increase luminal surface area for absorption.
Infoldings of the basal membrane to increase surface area
47
What are the 3 layers of the glomerular cell wall, and how do they control filtration?
Podocytes internally - surround the capillaries with pedicles which have small slit pores to restrict molecular size. Nephrin in the slit pores is negatively charged to repel proteins.
Basal membrane - also negatively charged
Endothelial membrane - fenestrations to only allow the passage of small molecules.
Substances with sizes greyer than 67 kDa (size of albumin) are restricted, with negatively charged molecules entering less easily.
48
What are the 3 areas of the loop of Henle and their histology?
Thin descending limb - squamous epithelium with few mitochondria
Thin ascending limb - Same as TDL
Thick ascending limb - Cuboidal epithelial cells rich in mitochondria (same as the proximal tubule, without the brush border)
49
What are the two final areas of a nephron and their histology?
Distal tubule - Cuboidal epithelial cells with lots of mitochondria and without a brush border
Collecting duct - Principle cells (Na+ regulation) and intercalated cells (acid-base balance)
50
What is the rate of renal filtration? In terms of: % blood flow, mL/min and L/day
20% of plasma volume
125 mL/min
180 L.day
51
What are the 3 properties that the glomerulus discriminates against when filtering?
Size
Negative charge
Shape
52
What is the equation that calculates GFR?
Starling equation
GFR = Kf x (Pc + Ob - (Pb + Oc)
```
Kf = filtration coefficient (surface area x permeability)
Pc = hydrostatic pressure of capillary
Pb = hydrostatic pressure of Bowman’s space
Oc = oncotic pressure of capillary
Ob = oncotic pressure of Bowman’s space
```
53
What is the net filtration pressure of a glomerulus with these figures?
```
Pb = 20mmHg
Ob = 3mmHg
Pc = 60mHg
Oc = 25mmHg
```
Net = Pc+Ob - (Pb + Oc)
= 60 + 3 - (20+25)
= 63 - 45
= 18mmHg
54
What are the different mechanisms which are used to hold the GFR steady?
Contraction of Mesangial cells in bowman’s capsule, decreasing surface area and, therefore, reducing filtration coefficient
Myogenic mechanism - systemic but important in AFFERENT arterioles. When a blood vessel dilates, it becomes more permeable to Ca2+, causing smooth muscle contrition and restriction of the blood vessel, reducing flow.
Flow dependant mechanism - decreased blood flow decreases GFR, which slows filtrate and increases Na+ resorption in the early distal tubule lowering amount in the filtrate. Macula densa senses decreased Na+ in filtrate. Causes decrease in afferent arteriole resistance and release of Renin which activates the RAA system. This increase blood pressure and, therefore, GFR through various different mechanisms.
55
What are the two main substances used to measure GFR?
Inulin as none is reabsorbed or secreted so concentration in ruing = GFR. However, invasive as inulin is not found in the body so requires IV.
Creatinine (muscle breakdown product) more commonly used to get an ‘estimated GFR’. Not as accurate as although it is freely filtered, it is also secreted by the peritubular capillaries so it is an overestimate.
Also varies on muscle mass so people with more can have higher clearance and still be normal.
Formulas are used to approximate GFR based on serum creatinine, taking into account age, gender and weight.
56
What is Tmax?
The maximum concentration of a substance that can be reabsorbed by the kidney before it starts appearing in the urine. Glucose is a good example, before 200mg/100ml all can be reabsorbed. After this point the kidney cannot filter any more out so any increase in blood glucose after that point leads to increased glucose in the urine.
Limited by number of transport proteins - occurs when all transporters are saturated.
57
Why does the kidney have the process of filtration and reabsorption rather than purely excretory.
1) Only transporters for essential substances are required
2) Water balance can be controlled by a reabsorpative process
3) Requires less energy as many solutes can be reabsorbed with Na+
58
What is the basic process for solute reabsorption in the kidneys?
1º active transport in the basal membrane to maintain cellular homeostasis (Na+/K+ ATPase)
2º active transport in the luminal membrane, where specialised carriers transport Na+ down its concentration gradient with other molecules (glucose, amino acids etc.)
Other solute efflux pathways on the basal membrane to remove things other than Na+ into the interstitial fluid.
59
How are solutes absorbed into the peritubular capillaries from the interstitial fluid?
Accumulation of H2O = high interstitial fluid hydrostatic pressure
Efferent arteriole is narrow so decreased capillary hydrostatic pressure.
Proteins remain in the blood, giving it a high colloid oncotic pressure.
ALL of which favour absorption!
60
Describe the difference parts of the nephron, the solutes which are absorbed and secreted in each of the different areas.
```
Proximal tubule (Iso-osmotic)
Reabsorbed = Na+, Cl-, HCO-, K+, H2O, glucose and amino acids (65%)
Secreted = H+, organic acids, organic bases
```
Thin descending loop of Henle (Hypo-osmotic)
Reabsorbed = H2O
Secreted = nothing
Thick ascending loop of Henle (Hype-rosmotic)
Reabsorbed = Na+, Cl-, K+, Ca2+, HCO3-, Mg2+ (25%)
Secreted = H+
Distal tubule
Reabsorbed Na+, Cl-, Ca2+, Mg2+
Secreted = nothing
Collecting ducts
Principle cells = Na+ balance
Intercalated cells = acid-base balance
61
Describe the counter current mechanism in the Loop of Henle which is required to concentrate the interstitial fluid within the kidney.
Pumps in the thick ascending loop are capable of creating a 200 mOsm/L gradient between the filtrate and the interstitial fluid.
Water leaves the thin descending loop by osmosis to equalise the concentration in the loop and interstitial fluid. This concentrates the filtrate, making it hyper-osmotic.
The hyper-osmotic fluid moves into the thick ascending loop where solutes are pumped out into the interstitial fluid. This makes: the interstitium more concentrated by 200 and also makes the filtrate hypo-osmotic.
A repetition of this process allows the interstitium to concentrate to 1500, equal to that of the most concentrated urine.
62
How are solutes absorbed in the proximal tubule?
Mainly through 2º active transport with Na+
Basal Na+/K+ ATPase created a diffusion and electrochemical gradient within the epithelial cell which allows Na+ to move across through facilitated diffusion with other molecules (glucose, amino acids, Cl-)
Hydrogen is extruded through a Na+/H+ exchanger
Ca2+ enters though luminal channels, down the electrochemical gradient set up by Na+
63
How does ADH concentrate the urine?
ADH acts on the distal tubule and the collecting ducts to increase permeability to H2O and cause increased osmosis.
At the end of the Loop of Henle, filtrate is around 100 mOsm/L (1/3 concentration of plasma). This is the concentration of urine when no ADH is present.
ADH binds to V2 receptors in epithelial cells, increasing cAMP generation and activation of PKA which causes fusion of aquaporin 2 with the luminal membrane. This forms channels through which water can flow easily, down the gradient achieved through the counter current mechanism. This allows concentration of urine up to 1500 mOsm/L!
64
What is diabetes insipidus?
A disorder in which ADH secretion by the anterior pituitary fails, causing the symptoms commonly seen in diabetes, but without the raised blood glucose.
Polyurea, nocturea, polydipsia
65
What are the two functions of the kidney in terms of acid-base balance?
Secretion of non-volatile acids (HCl, H2SO4, etc.)
Regeneration of HCO3(4-) lost in the buffering of organic acids.
66
What is the cellular mechanism for the regeneration of HCO3(4-) in the renal epithelium?
Carbonic anhydrase catalyses hydration of H2O and CO2 to H2CO4 which dissociates —> HCO3(4)- + H+
HCO3(4-) is removed into the interstitial fluid and then back into the blood via efflux pumps.
H+ is excreted into the lumen of the nephron.
67
What are the two different things that can happen to H+ in the lumen of the nephron?
Reacts with HCO3(4-) to form CO2 and H2O (catalysed by carbonic anhydrase)
CO2 is reabsorbed into the epithelial cells where it is again converted by carbonic anhydrase to regenerate HCO3(4-)
Reacts with urinary buffers (HPO42-, H2PO44-, NH3). These are then lost in the urine, removing H+ from the body.
68
How is H+ excreted into the nephron lumen from the epithelial cell?
Mainly through Na+/H+ antiporters in the proximal tubule.
H+ ATPases in the intercalated cells of the collecting ducts
69
What are the classes and main causes of obstructive uropathy?
Partial, complete, bilateral, unilateral
Congeintal abnormalities (stenosis, valve, stricture, vesicoureteral reflux)
Urinary calcuil
Benign prostatic hypertrophy
Tumors (kidney, ureters, bladder, prostate)
External compression (tumors, mass)
Inflammation (prostatitis, ureteritis, uretitis)
Blood clots / necrotising papillae
Pregnancy
Uterine prolapse (cystocele)
Functional disorders (spinal abnormalities)
70
What is hydronephrosis?
Hydronephrosis is a dilation of the ureters and renal pelvis, with back flow of urine through the renal calyces/tubules etc. into the blood.
Caused by obstruction of outflow of urine
Characterised by blunted calyces, thinned cortex and dilated pelvis.
71
Why does renal obstruction cause kidney damage?
Significant interstitial inflammation and corticular atrophy which destroyed nephrons which cannot then be replaced.
In late stage kidney obstruction the organ becomes almost a ’thin walled cyst’ with no filtration potential.
72
What would the clinical features of an acute kidney obstruction be?
Severe pain due to distention of collecting system.
Symptoms usually due to where the cause (calculi) is:
Bladder = dysurea, nocturea, difficult urination, hesitancy, retention
Ureter = renal colic
73
What would the clinical features of a unilateral complete obstruction be?
May remain silent for long periods of time.
Unfortunate that it remains asymptomatic because if caught early damage is reversible.
Can lead to chronic kidney damage in the effected kidneys.
74
What would the clinical features of bilateral partial kidney obstruction?
Inability to concentrate urine = polyurea and nocturea
Hypertension is common
75
What would the clinical features of complete bilateral kidney obstruction be?
Oligurea / anurea
| Incompatible with life after a certain period, if the blockage isn’t removed.
76
Where are the 3 positions urinary calculi are most likely to be found + why?
The three narrowings of the ureter.
Uretopelvic junction
Crossing of the pelvic brim at the branching of the common iliac vessels
Entry to the bladder (vesicoureteral junction). The ureter passes through the wall of the bladder for a few cm before entering the bladder at an oblique angle. This forms a physiological sphincter. When the bladder contracts it closes the ureter and prevents reflux.
77
What are the main causes of urinary calculi formation?
Most important is an increase of solute excretion above the solubility in the filtrate (supersaturation). This causes crystals to precipitate out of solution.
Infection and bacterial presence (mainly Proteus mirabilis)
Stasis of urine flow (in similar way to thrombogenesis)
78
What are the common manifestations of renal calcuil, large and small?
Small = most dangerous as can pass into the ureters causing renal colic and obstruction.
Large = remain in the renal pelvis/calcuil. Cause partial obstruction but nothing major. Usually manifest by haematurea.
Also predispose the patient to renal superinfection
79
What are the common tumours of the kidney?
```
Benign:
Papillary adenomas (rarely causes clinical problems)
Oncotocytoma (although benign, can grow very large ~10cm and cause obstruction )
```
Malignant (1º and 2º)
1º = Renal cell carcinoma (adenocarcinoma of kidney)
these account for ~85% cancers of kidney. Arise from the tubular epithelium
1º = Urothelial (transitional cell) carcinomas of pelvis
2º = uncommon
80
What are the common metastatic paths of carcinomas and sarcomas?
Carcinomas = of endodermal origin
Usually lymphatic spread
Sarcomas = of mesenchymal origin
Usually haematogenous spread
81
What are the classifications of renal adenocarcinoma?
Clear cell type = large cells with lots of glycogen containing cytoplasm, usually well differentiated.
Papillary type = from distal tubules (commonly haemorrhagic and cystic)
82
What are the features of uncomplicated and complicated UTI?
```
Uncomplicated:
Occurs in healthy individuals
Usually women
Usually cystitis
Increased risk factors (antimicrobials, Sex, reduced oestrogen and concomitant reduction of lubrication)
```
Complicated:
Occurs when something is abnormal within the patient (anatomically or metabolically e.g. vesicoureteral reflux and immunocompromised)
Also occurs in pregnancy
83
Why are UTIs in pregnancy dangerous?
Cn induce labour
Can lead to preeclampsia
Can lead to septicaemia and possible stillbirth.
84
What are the steps to take when a patient presents with macroscopic heamaturea?
Exclude UIT (dipstick, MSU)
Exclude neoplasm (Ultrasound, cytoscopy, CT)
85
What are the 3 cell types within the glomerulus?
Podocytes = epithelial cells
Endothelial cells
Mesangial cells
86
What is the mesangial cell of the glomerulus and what is its function?
Secretes the mesnagium = extracellular matrix
Phagocytosis and exocytosis of trapped residue and aggregated proteins
Structural support for the glomerulus
Modulation of glomerular distention - regulate glomerular distention in response to blood pressure.
87
Why might high levels of urea or creatinine be found in the blood?
Failure of excretion by the kidneys.
88
Why might low levels of Ca2+ be found in the blood?
Falure of hydroxylation of 25OH-D3 to 1,25OH-D3 by the enzyme 1-alpha hydroxyls within the kidney.
89
Why might high levels of phosphate be found in the blood?
Failure of secretion within the nephron of the kidney.
90
Why might high levels of PTH be found in the blood of patients with chronic kidney failure and what is the consequence of this?
Increased levels of phosphate cause the release (PTH normally reduces reabsorption of phosphate),
Causes increased levels of alkaline phosphatase in the blood due to release from bone,
91
Why would urine protein levels be high in chronic kidney failure?
Failure of the glomerular filtration barrier, allowing small proteins to mass though (mainly albumin)
92
Why would blood Hb be low in chronic kidney failure?
No production of EPO by the kidneys which acts to increase proliferation of the pro-erythroblast lineage.
93
What is the main cause of mortality in chronic kidney failure?
Vascular disease causing heart failure
Calcification of arteries, causing reduction in elasticity.
Complicated but involves:
- high phosphate levels,
- high PTH levels,
- low levels of chemicals which keep calcium phosphate crystals in solution
- conversion of myocytes in tunica media of muscles into osteoblasts
94
Why is arterial (aortic) elasticity very important?
```
Reduces after load on left ventricle
Decreases end organ perfusion pressure
Decreases stresses on artery itself
Maintains BP
Maintains perfusion of cardiac vessels which are perfused in diastole.
```
95
What are the main hormones which act on the kidney?
```
Aldosterone
Angiotensin 2
ADH
Atrial Natriuretic Peptide
PTH
```
96
Aldosterone’s effect on the kidney
| What, how, where
What =
Increased Na+, Cl-, H2O resorption and increased K+ secretion
How =
Increased activity of basal Na+/K+ ATPase on tubule cell basal membrane. Increased permeability of luminal membrane to Na+
Where =
Collecting tubule and ducts
97
Angiotensin 2’s effect on the kidney
| What, how, where
What =
Increased resorption of: Na+, Cl-, H2O and increased H+ secretion
```
How =
Stimulation of aldosterone secretion from adrenal cortex
Efferent arteriole constriction
Stimulation of basal Na+/K+ ATPase
Stimulation of luminal Na+/H+ pump
```
Where =
TAL of Henle, distal tubule, collecting ducts
98
ADH’s effect on the kidney
| What, how, where
What =
Increases H2O reabsorption
How =
Formation of H2O channels by aquaporin 2.
Activation of receptor —> increased cAMP —> protein kinase activity —> binding of AQP-2 with luminal membrane
Where =
Distal tubule, collecting tubule and duct
99
ANP’s effect on the kidney
| What, how, where
What=
Decreased Na+ / Cl- reabsorption
```
How =
Increases GFR
Suppresses renin secretion
Suppresses aldosterone secretion
Actively decreases Na+ reabsorption
Increases blood flow in vasa recta
```
Where = TAL of Henle onwards
100
PTHs effect on the kidney
| What, how, where
What =
Decreases phosphate reabsorption
Increases Ca2+ reabsorption
How =
??
Where =
Proximal tubule,loop of Henle, distal tubule
101
How can the level of inulin be worked back to calculate GFR (equation)?
GFR = (U x V) / Pa = C
```
U = urine concentration
V = urine flow rate
Pa = plasma concentration
C = clearance rate
```
This works because inulin is neither reabsorbed or secreted on the L of H
(125 x 1) / 0.5 = 250
If 125mg was filtered in 1 min and the plasma concentration was 0.5mg then 250mg of blood would have to be filtered in 1 min.
= GFR
= 250ml/min
102
What are the 3 types of acute renal failure? Describe them.
| Give examples of each.
Pre-renal acute renal failure.
= failure resulting from reduced blood supply to the kidneys
= heart failure, hypotension, shock, haemorrhage, renal artery stenosis
Intra-renal renal failure
= failure deu to abnormalities within the kidney
= blood vessels, glomerular nephritis, necrosis etc.
Post-renal renal failure
= failure due to obstruction of outflow.
= Calculi, prostatic hypertrophy, congenital, etc.
103
Describe the process of pre-renal failure.
Low blood supply —> reduced GFR —> accumulation of H2O and solutes —> reduced urine output —> olugurea/anurea
A very low blood supply (20-25% normal) can result in infarction of the kidneys and resultant ischaemia. This destroys glomeruli and is irreversible. Ischaemic time of the kidney = 20-30mins
This causes progression to INTRA-RENAL FAILURE
104
Describe the process of glomerular nephritis.
Antibody mediated damage to glomeruli (usually post infection)
Precipitation of antibody/antigen complexes
Trapped in glomeruli
Blockage of glomeruli
(Type 3 hypersensitivity reaction)
105
What are the physiological effects of acute renal failure?
Retention of H2O in blood —> increased hydrostatic pressure —> oedema + hypertension
Retention of potassium = hyperkalaemia
H+ retention can cause metabolic acidosis
(Patient can die within 2 weeks of cardiac failure if no treatment is given)
106
How is H+ homeostasis maintained in the body?
Kidney and lungs.
Lungs:
The majority of CO2 is carried in the blood as bicarbonate ions. Carbonic anhydrase forms this into CO2 and H2O. To reduce blood bicarbonate, and therefore, H+, respiration rate increases and more CO2 is given off.
Kidney:
H+ is secreted into the lumen by H+/Na+ exchangers. This is combined with bicarbonate to form H2CO3 which is broken down by carbonic anhydrase to CO2 and H2O. These diffuse into the renal tubular cells and reformed into H2CO3. Bicarbonate can then be reabsorbed into the blood and H+ secreted. This causes loss of H+ without loss of HCO3-.
H+ can also combine with buffers in the filtrate (NH3 --> NH4+) which are then excreted.
The majority of acid homeostasis in the kidneys occurs in the intercalated cells of the collecting ducts.
alpha intercalated cells secrete acid!!
beta intercalated cells secrete base!!
107
What are hyaline casts?
Quite normally found in the urine.
Only suggestive that the patient had concentrated urine at the time of collection. Very common after exertion and during febrile states.
Formed by strands of "Tamm-Horsfall" proteins that are secreted by the thick ascending limb and coagulate into a gel-like structure when there is moderate stasis of urine.
