Kidneys and Blood Pressure
PKGhatak, MD
A Blood Pressure (BP) of 120 mm Hg systolic and 80 mmHg diastolic, expressed as 120/80 mm Hg, is considered a normal BP in adults. When BP is over 140/80, it is called hypertension. In about 80% of cases, no definite cause of high BP will be detected. This is called Essential or Primary Hypertension. About 5 to 20 % of cases of high BP are due to kidney diseases.
Role of Kidney in maintaining a normal BP.
There are two systems that are operative. One is the Sympathetic nervous system and the other is the Angiotensin-Renin-Aldosterone system. These two systems are interconnected and act in a coordinated manner.
A. Sympathetic systems.
The BP sensors are located in the baroreceptors of Carotid bodies and Aortic bodies in the Aortic Arch. Any change in BP, high or low, initiates an impulse in the carotid stretch receptors in the carotid bodies and is carried by the Glossopharyngeal nerve and then relayed to the Hypothalamus. The pressure receptors of the aortic arch are sensitive only to falling BP. The Vagus nerve carries the sensation to the center and then relays it to the hypothalamus. From the hypothalamus, the outgoing impulse goes to the Celiac Ganglia. The postganglionic alpha fibers innervate all the systemic arteries and the beta fibers supply the heart.
The Hypothalamus also sends impulses to the adrenal glands and to the Juxtaglomerular cells of the kidneys.
Venous BP monitors: These are low-pressure monitors.
These monitors exist within large veins, pulmonary vessels, and within the walls of the right atrium and ventricle. Changes in volume influence the baroreceptors in the venous system and lead to the secretion of antidiuretic hormone and renin.
Effect of sympathetic alpha stimulation.
Arterial walls respond to alpha stimulation by increasing the tone of the muscular wall and the BP is raised. When the BP is high, the carotid body receptors produce a negative response in the hypothalamus, it prevents the further rise in BP. When BP falls, the aortic body sends positive impulses to the hypothalamus and BP is raised.
Effect of sympathetic Beta stimulation. Beta fibers mainly supply the heart. Stimulation of the beta fibers increases heart rate and force of ventricular contraction and elevation of BP.
Effect of sympathetic stimulation of Adrenal glands. It increases the production and release of Aldosterone.
Effect of sympathetic stimulation of juxtaglomerular cells. It causes the secretion of Renin.
The action of the sympathetic system
|
Agent |
Substrate |
Response |
Final effect |
|
Alpha stimulation |
Arterial wall |
Vasoconstriction |
BP elevation |
|
Beta stimulation |
Heart muscles |
Rate and force of contraction |
BP elevation |
|
|
Adrenal Glands |
Aldosterone release |
Increased Na+ absorption in exchange for K+ |
|
|
Juxtaglomerular cells |
Renin release |
Angiotensin I formation |
|
|
Posterior Pituitary |
ADH release |
Blood volume increase |
B. Angiotensin-Renin-Aldosterone system.
BP sensors.
The outer wall of the afferent arteriole of the kidney contains BP sensors. When blood flow/ pressure is low these cells secrete Paracrine molecules (paracrine are chemicals, have actions like hormones but these chemicals are locally released and locally active). These molecules stimulate Juxtaglomerular cells to produce and release Renin.
Electrolyte sensors.
The Macula Densa cells of the distal convoluted tubules are specialized endothelial cells. They continuously monitor Sodium and Chloride concentrations of the glomerular fluid. Any fall in sodium chloride concentration triggers the paracrine release. Paracrine increases the rate of excretion of Potassium+ ion and H+ion production and release in exchange for Sodium+ ion from the filtrate.
Angiotensinogen is an alpha2 globulin produced by the liver and renal endothelial cells and circulates in the blood and is a non-active molecule. Renin converts angiotensinogen to angiotensin I. Angiotensin I is carried by the renal veins to the inferior vena to the right side of the heart and then to the lungs. In the pulmonary capillaries, the endothelial cells secrete Angiotensin Converting Enzyme (ACE). ACE converts angiotensin I to angiotensin II. In the blood, angiotensin lasts about 30 seconds and in the tissues for about 15 minutes then it is degraded by ACE to Angiotensin III and Angiotensin IV. Both angiotensin III & IV have variable effects but are in the same line as angiotensin II.
Angiotensinogen is also produced by the fat cells, testicles, ovaries, brain, heart and blood vessels. In these secondary locations, its functions are limited at the local tissue levels.
Effect of Angiotensin II:
Angiotensin II has a multitude of functions. 1. It increases the tone of all systemic arteries and veins. 2 Constricts afferent and efferent arterioles of the glomerulus. and thereby increases filtration pressure and the GFR (glomerular filtration rate) is increased. 3. Angiotensin II increases the rate of Na+ ion reapportions in the proximal tubules. 4. It accelerates Na+/K+ H+ exchange in distal convoluted tubules. 5. Angiotensin II causes the secretion of aldosterone by the adrenal cortex. 6. It releases an Antidiuretic hormone from the Posterior pituitary gland.
Na+/K+H+ ion exchange and water reabsorption produce an increase in total body Sodium and a decrease in potassium. The total body intravascular volume expansion takes place. The serum becomes alkalotic due to execs HCO3- ions. This condition is called Hypokalemia alkalosis.
Effect of Anti Diuretic Hormone (ADH).
ADH increases water absorption in the collecting tubules from the filtrate, thereby increasing blood volume. However, expansion of blood volume takes place only when both kidneys are ischemic. If only one kidney remains normal then increased glomerular filtrate and loss of Sodium and water by the normal kidney in the urine keep the blood volume normal but BP remains high.
Role of Kidneys in producing High BP:
Any condition producing a decrease in blood flow in the Kidneys (ischemic) produces high BP.
Renal causes of hypertension are discussed under
Renal- vascular
Renal parenchymal causes.
Of all the causes of Hypertension, renovascular hypertension has the most potential to be cured by corrective surgery and usually, the patients are not required to take BP medications. It is essential to find the cause of high BP before much damage takes place.
1. Common causes of Renovascular hypertension.
In children:
Common causes are coarctation of the aorta, Moyamoya disease. Kawasaki disease, Takayasu arteritis, renal artery trauma, congenital renal artery hypoplasia or renal artery stenosis and renal graft stenosis following renal transplantation.
Moyamoya disease is more prevalent in Japan and is probably inherited by autosomal dominant inheritance. Cerebral arteries are deformed and various degrees of neurological symptoms develop at a very early age. Kawasaki disease is a multisystem inflammatory disease that usually follows a viral infection and produces signs and symptoms involving the skin, mucous membrane and lymph nodes and internal organs. It is more prevalent in China. Takayasu arteritis is an inflammatory disease of the aorta and its main branches producing narrowing of blood vessels and aneurysms producing severe ischemia to the involved areas like arms, neck, brain and kidneys. There is no known cause and treatment is not effective. It is often seen in Japan, Mexico and India.
In adults:
The common pathology is renal artery stenosis due to atheromatous plaques.
The narrowing may be in one or both renal arteries. The plaques may be only segmental or in multiple areas, commonly involves the proximal third of the artery. The plaques develop the same way as in the coronary arteries. The risk factors are diabetes, high BP, high cholesterol, obesity, cigarette smoking, sedentary lifestyle and runs in family.
Other causes of renal artery diseases are Congenital stenosis, Renal artery thrombosis, emboli, aortic dissection, A-V malformation, and aneurysm of the abdominal aorta.
In young females:
Fibromuscular dysplasia. This condition is largely confined to females of childbearing age. The condition may run in families. The medium size arteries are involved. Common sites are renal, intracranial, face and abdominal. The distal 2/3rd of the renal artery shows dysplasia. The changes may be confined in one or all three layers of the arterial wall. Bead-sized aneurysms are seen in cerebral branches of carotid arteries.
Risk factors are female hormones, the higher incidence of methysergide use in migraine, cigarette smoking, alpha 1 antitrypsin deficiency, cystic medial necrosis, neurofibromatosis, coarctation of the aorta and Ehler-Danlos syndrome.
The patients with fibromuscular hypoplasia are mostly symptoms free. A cerebrovascular episode like TIA, (transient ischemic attack) or subarachnoid hemorrhagic may lead to a diagnosis of fibromuscular dysplasia of the renal artery.
2. Renal parenchymal diseases cause hypertension.
Almost all inflammatory diseases of the kidneys raise BP. A few common conditions are: -
Polycystic disease of the kidney. Glomerulonephritis.
Polycystic disease of the kidney is the most common hereditary kidney disease in adults causing hypertension and other complications. It is inherited as a dominant mode, and the expression of the defective gene penetration is variable. In children, the disease is much less aggressive and provides a better prognosis.
Glomerulonephritis is generally due to post-streptococcal pharyngitis, also seen in secondary to Bacterial endocarditis, Hepatitis B, hepatitis C, HIV infection and now COVID -19. Other less common causes are autoimmune glomerulonephritis. Lupus, Goodpasture syndrome, IgA nephropathy, Diabetic microvascular disease,
Investigation and Diagnosis:
The renal parenchymal disease is evident by the presence of protein, RBC, red cell casts and granular casts in the urine. If active infection is present, an increased number of WBCs and WBC casts are detected in urine. Further tests, including IgG, IgA and other serological tests are generally required for the determination of the etiology in individual cases. In most cases, needle biopsy of the kidney and special immunological staining is required to properly direct medical therapy and evaluate prognosis.
Renovascular disease is detected by an Ultrasonography of the abdomen. It is a noninvasive test and can easily detect abdominal aortic aneurysm, dissection of the aorta, atheromatous changes and fibromuscular dysplasia. The new generation Doppler ultrasound study gives flow and degree of stenosis. In case the presence of gas in the bowel interferes with the ultrasound study MRI is an excellent alternative. The functional status of kidneys is determined by serum creatinine, urinary creatinine and GFR, electrolytes. Radio-opaque dye administration is held off till a definite surgery is planned. In a situation that is likely to be associated with vascular abnormalities of the brain and other vital organs, then a whole body angiogram may be completed before surgery.
Treatment:
Renal artery stenosis is treated by angioplasty and stent placement. This is the preferred treatment for fibromuscular dysplasia and a stent often is not needed.
Resection, repair and Dacron graft are used based on the nature of the pathology. In unilateral and atrophic kidney nephrectomy is indicated. Post-surgery prognosis is very good for children and young individuals.
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