Kidney disease Flashcards
How is filtrate formed in the kidneys?
The renal corpuscle forms the filtrate from blood that is free of cells, larger polypeptides and proteins
This filtrate then leaves the renal corpuscle and enters the tubule
As it flows through the tubule substances are added or removed from it e.g. salts (NaCl), urea
Ultimately, the fluid remaining at the end of each nephron combines in the collecting ducts and exits as urine.
What are the four processes that occur in the kidneys?
- Filtration
- Reabsorption
- Secretion
- Excretion
What is the structure of the nephron
Bowman’s capsule
Loop of Henle –> consists of a descending limb from the proximal tubule and an ascending limb leading to the distal convoluted tubule
- Counter current multiplier system –> two different directions, left hand side very permeable to water, encourages water reabsorption facilitated by aquaporins. Right hand side, not very water permeable, NaCl reabsorption.
Fluid flows from the distal convoluted tubule into the collecting ducts system, which is composed of the cortical collecting-duct system
What does the kidney control?
Total body water
Electrolytes - Na, Ca and Mg –> reabsorbed
- K –> absorbed
pH –> 7.4
Nitrogenous waste materials –> urea
Endocrine
- Erhyropoietin –> link to blood volume, kidney stimulate RBC production from stem cells if volume low
- Renin –> blood pressure regulation
- Vitamin D –> calcium absorption from gut
How do the kidneys help with blood pressure control?
Blood pressure regulation is determined by cardiac output and diameter of blood vessels/ resistance.
Blood vessel diameter and resistance involves renin which is released by the kidneys
The more your heart pumps out and the smaller the bv diameter the higher the blood pressure
Control of fluid volume in the blood will have an affect on bp. The more fluid the higher the bp
Discuss the renin-angiotensin-aldosterone system
Mechanism
Juxtaglomerular apparatus responds to 3 types of stimulation
- reduced salt
- reduced pressure
- adrenoreceptor stimulation
In response to this the kidney releases renin –> an enzyme which enters the blood stream
At the same the liver is producing Angiotensinogen
Renin cleaves Anigotensinogen to form Angiotensin 1 which remains in circulation around the lungs.
The lungs produce an enzyme called ACE which then helps with mediating bp
ACE cleaves Angiotensin 1 to Angiotensin 2
Angiotensin 2 can bind to a number of different cell receptors and stimulate a number of processes
- Sympathetic activity
- Increase the number of proteins to be embedded into the tubular causing an increase in Na reabsorption, passive affect is then absorbing more H2O (can also be hormone stimulated - aldosterone) Also stimulates K excretion and Cl reabsorption
- Adrenal gland secretes aldosterone, lipid based steroid hormone (can diffuse across plasma membrane quickly)
- Arteriolar vasoconstriction –> increase in blood pressure
- ADH mediated secretion mediated by the pituitary gland causing H2O absorption in the collecting duct
Mechanisms are in place to reduce the physiological strain on the body which caused the body to produce renin in the first place.
Occurs in normal physiological states
What is the rate of glomerular filtration?
The volume of fluid filtered from the glomeruli into Bowman’s space per unit time is known as glomerular filtration rate (GFR)
GFR is determined by net filtration pressure, the permeability of the corpuscular membranes, osmotic force of any proteins there, and the surface area available for filtration. Large surface area helps with effectiveness
Average person –> renal blood flow is 180L/day / 125ml/ min
Total plasma volume in the circulatory system is around 3L, so the kidneys filter the entire plasma around 60 times per day. Efficient mechanism for waste product removal as it filters so quickly
This allows the kidneys to rapidly regulate the constituents of the internal environment and excrete large quantities of waste products
What is acute kidney injury?
AKI is defined as an abrupt (within hours) decreases in kidney function, which encompasses both injury (structural damage) and impairment (loss of function)
- AKI is the same as acute renal failure
It is a syndrome that rarely has a sole and distinct pathophysiology
Many patients with AKI have a mixed aetiology where the presence of sepsis, ischaemia and nephrotoxicity often co-exist and complicate recognition and treatment
What are the causes of AKI?
Pre-renal –> relate to decreased perfusion pressure
Post-renal –> obstructive
Intrinsic –> related to pathology of the vessels, glomeruli, or tubules-intestitium
If the Pre and or post renal conditions persist, they will eventually evolve to renal cellular damage and hence intrinsic renal damage
What are the intrinsic causes of AKI?
Tubular
- Renal ischaemia –> e.g. complication of surgery, pancreatitis, pregnancy, trauma
- Nephrotoxic drugs –> antibiotics, antineoplastic drugs, anaesthetic drugs, heavy metals
- Endogenous toxins –> myoglobin, haemoglobin, uric acid (in proper breakdown can be toxic)
Glomerular
- Acute post-infectious glomerulonephritis
- Lupus nephritis
- IgA glomerulonephritis
Interstitium
- Infections –> bacterial, viral
- Medications
Vascular
- Large vessels –> bilateral renal vein thrombosis
- Small vessels –> vasculitis, malignant hypertension, atherosclerosis
How can AKI lead to multi-organ injury?
AKI leads to distant organ injury through a combination of pro-inflammatory and oxidative stress-mediated mechanisms
Serum and distal organ cytokine levels (IL1, IL6, IL10 and TNFa) cause an increase in immune system response by increase leukocyte trafficking (neutrophil, lymphocyte and macrophage) and increased oxidative stress (glutathione depletion).
In addition, sodium and water channel dysregulation in the lungs in aggravate pulmonary oedema.
What is chronic kidney disease?
Presence of kidney damage or estimated glomerular filtration (eGFR) less than 60ml/min/1.73m2, persisting for 3 months of more, irrespective of the cause. –> 50% of functional reserve from kidney lost (normal value 120)
Progressive loss of kidney function ultimately resulting in the need for renal replacement therapy (dialysis or transplantation)
Kidney damage refers to pathologic abnormalities either suggested by imaging studies or renal biopsy abnormalities in urinary sediment or increased urinary albumin excretion rates.
Patients rarely recover from CKD
Chronic and sustained insults from chronic progressive nephropathies (cause loss of function) evolve to progressive kidney fibrosis and destruction of the normal architecture of the kidney.
This affects all 3 compartments, mainly glomeruli, the tubules, interstitium and the vessels.
It manifests histologically as glomerulosclerosis (scaring), tubulointerstitial fibrosis and vascular sclerosis
What are the units of GFR?
ml/min/1.73m2
What is the pathophysiology of of CKD?
Chronic and sustained insults from chronic progressive nephropathies (cause loss of function) evolve to progressive kidney fibrosis and destruction of the normal architecture of the kidney.
This affects all 3 compartments, mainly glomeruli, the tubules, interstitium and the vessels.
It manifests histologically as glomerulosclerosis (scaring), tubulointerstitial fibrosis and vascular sclerosis.
Reduced glomerular surface area which affects glomerular filtration rate.
The sequence of events which lead to scarring and fibrosis are complex, overlapping and are multistage phenomena.
Infiltration of damaged kidneys with extrinsic inflammatory cells
Activation, proliferation and loss of intrinsic renal cells through apoptosis, necrosis etc
Activation and proliferation of extracellular matrix e.g. connective tissue, producing cells including myofibroblasts (usually disappear during wound healing) - don’t undergo normal apoptosis
- Deposition of ECM replacing the normal architecture
Inflammatory cascade
What are the 5 stages of CKD and linked GFR?
Stage 1
- eGFR –> 90 or more ml/min/1.73m2
- Normal kidney function but with some kidney damage or disease
- e.g. Protein or blood in urine, kidney inflammation
Stage 2
- eGFR –> 60-89ml/min/1.73m2
- Mildly reduced kidney function AND you are already to have some kidney damage or disease.
- People with a eGFR or 60-80 without any known kidney damage or disease are not considered to have CKD
Stage 3 A & B
- eGFR –> A = 45-59ml/min/1.73m2 B = 30-44ml/min/1.73m2
- Moderately reduced kidney function –> with or without known kidney disease
Stage 4
- eGFR –> 15-29ml/min/1.73m2
- Severely reduced kidney function
Stage 5
- eGFR –> <15ml/min/1.73m2
- Very severely reduced kidney function
- Sometimes called end-stage kidney failure or established renal failure
There is an increased plasma concentration of Cystatin C with kidney damage as it is usually removed when kidney working healthily
High levels of creatinine also indicate CKD as its usually filtered out.
