Renal diseases and pathophysiology

Kidney function tests measure how efficiently your kidneys are working. Most of these tests check how well your kidneys clear waste from your system.

Urine Tests

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Glomerulonephritis is an inflammatory process that involves glomerular structures and damage the tiny filters of kidneys. 

Most cases of primary and many cases of secondary glomerular disease probably
have an immune origin. Although many glomerular diseases are driven by immunologic events, a variety of nonimmunologic metabolic (e.g., diabetes), hemodynamic (e.g., hypertension), and toxic (e.g., drugs, chemicals) stresses can induce glomerular injury, either alone or along with immunologic mechanisms.

Glomerulonephritis can be caused by various of factors including:

• Toxins or medicines.
• Viral infections, such as HIV, hepatitis B and C viruses.
• IgA nephropathy.
• Lupus-related kidney inflammation.
• Bacterial infections that commonly cause throat and skin infections, such as strep or staph bacteria.

Two types of immune mechanisms have been implicated in the development of glomerular disease:

1. Injury resulting from antibodies reacting with fixed glomerular antigens or antigens planted within the glomerulus;
2. Injury resulting from circulating antigen–antibody complexes that become trapped in the glomerular membrane

Glomerulonephritis signs and symptoms may include:

• Pink or cola-colored urine from red blood cells in your urine (hematuria)
• Foamy or bubbly urine due to excess protein in the urine (proteinuria)
• High blood pressure (hypertension)
• Fluid retention (edema) with swelling evident in your face, hands, feet and abdomen
• Urinating less than usual
• Nausea and vomiting
• Muscle cramps
• Fatigue

Glomerulonephritis is inflammation and damage to the filtering part of the kidneys (glomerulus). It can come on quickly or over a longer period of time. Toxins, metabolic wastes and excess fluid are not properly filtered into the urine. Instead, they build up in the body causing swelling and fatigue.

The clinical manifestations of glomerular disorders generally fall into one of five categories:

1. Nephritic syndromes (proliferative inflamatory response)
2. Rapidly progressive glomerulonephritis
3. The nephrotic syndrome (↑ permeability of the glomerulus)
4. Asymptomatic disorders of urinary sediment (i.e., -hematuria, proteinuria)
5. Chronic glomerulonephritis

Nephrotic syndrome is a condition that causes the kidneys to leak large amounts of protein into the urine.

https://www.nhs.uk/conditions/nephrotic-syndrome/#:~:text=Nephrotic%20syndrome%20is%20a%20condition,greater%20chance%20of%20catching%20infections.

It can develop as  a primary or secondary to changes caused by systemic disease such as:

• diabetes mellitus;
• SLE-Systemic lupus erythematosus

Nephrotic syndrome can sometimes occur as a result of a kidney problem or another condition, such as:

• glomerulosclerosis – when the inside of the kidney becomes scarred
• glomerulonephritis – inflammation inside the kidney
• an infection – such as HIV or hepatitis
• lupus
• diabetes
• sickle cell anaemia
• in very rare cases, certain types of cancer – such as leukaemia, multiple myeloma or lymphoma

https://www.nhs.uk/conditions/nephrotic-syndrome/#:~:text=Nephrotic%20syndrome%20is%20a%20condition,greater%20chance%20of%20catching%20infections.

Signs and symptoms of nephrotic syndrome include:

• Severe swelling (edema), particularly around your eyes and in your ankles and feet
• Foamy urine, a result of excess protein in your urine
• Weight gain due to fluid retention
• Fatigue
• Loss of appetite

Types can be devided into primary and secondary nephrotic syndromes. 

Primary nephrotic syndrome

• Minimal change disease;
• Membranous glomerulonephritis;
• Focal segmental glomerulosclerosis;

Secondary nephrotic syndrome (occurs because of another disease or another cause)

• Systemic lupus erythematosus IV;
• diabetic neuropathy;
• amyloidosis;
• Hepatitis A and B;
• HIV

Answer: diabetic neuropathy

Answer: diabetic neuropathy

The nephrotic syndrome is not a specific glomerular disease but a constellation of clinical findings that result from an increase in glomerular permeability and loss of plasma proteins in the urine. 

In neprotic syndrom podocytes are injuried due to many reasons. Mainly from:

• immune complex deposition;
• complement protein activation → damage

The manifestations of CKD include:

• an accumulation of nitrogenous wastes;
• alterations in water, electrolyte, and acid–base balance (urinating more or less);
• mineral and skeletal disorders;
• anemia and coagulation disorders;
• hypertension and alterations in cardiovascular function (hypertension);
• gastrointestinal disorders (Nausea, vomiting);
• neurologic complications (Fatigue, weakness, sleep problems)
• disorders of skin integrity (dry, itchi skin);
• disorders of immunologic function

CKD can result from a number of conditions that cause permanent loss of nephrons, including diabetes, hypertension, glomerulonephritis, systemic lupus erythematosus, and polycystic kidney disease.

Hypertension and diabetic kidney disease are the two main causes of CKD in the United States

CKD can be caused by:

• high blood pressure (hypertension)– over time, this can put strain on the small blood vessels in the kidneys and stop the kidneys working properly (one if the most common cause)
• diabetes – too much glucose in your blood can damage the tiny filters in the kidneys
• high cholesterol – this can cause a build-up of fatty deposits in the blood vessels supplying your kidneys, which can make it harder for them to work properly
• kidney infections
• glomerulonephritis – kidney inflammation
• polycystic kidney disease – an inherited condition where growths called cysts develop in the kidneys
• blockages in the flow of urine – for example, from kidney stones that keep coming back, or an enlarged prostate
• long-term, regular use of certain medicines – such as lithium and non-steroidal anti-inflammatory drugs (NSAIDs)

https://www.youtube.com/watch?v=fv53QZRk4hs

CKD is a condition in which the kidneys are damaged and cannot filter blood as well as they should. Because of this, excess fluid and waste from blood remain in the body and may cause other health problems, such as heart disease and stroke.

CKD is defined as either kidney damage or a glomerular filtration rate (GFL) less than 60 mL/min/1.73 m² for 3 months or longer

Normaly blood urea gets excreted through the urine. During decreased glomerular filtration rate (GFL), less urea gets filtered out and therefore it has no where else to go besides the blood. Urea starts build up in the blood, which conditions is called azotemia. 

1. Azotemia

Azotemia can cause → general symptoms: nausea, loss of appetite; 

Azotemia can cause → CNS related symptoms: Encephalopathy - asterixis (tremor of the hands);

Azotemia can cause → pericarditis and increase chances of bleeding, because excess of urea makes less likely platelets to stick with each other (less clot formation)

Azotemia can cause → uremic frost → urea cristals deposit in skin, and they look like powdery snowflakes 

2.Hyperkalemia

In addition to get rid of waste, kidneys play an important role at electrolite balance. Potassium (K⁺) levels are particularly important and normaly the kideny helps with potassium excretion. In CKD, just like with urea, less potassium is excreted and so more builds in the blood. This leads to hyperkalemia

Hyperkalemia → cardiac arrythmias 

3. Disbalance in calcium level:

↓ Glomerular filtration rate → ↓ of activation of Vitamin D → ↓ Ca²⁺ absorption from the diet → hypocalcemia (low Ca level) → Parathyroid hormone release → bones lose Ca²⁺ → Renal osteodystrophy (bones become weak and brittle) 

4. Hormonal disbalance:

↓ Glomerular filtration rate → renin hormone release → increase blood pressure → hypertension → ↓↓↓ Glomerular filtration rate

↓ Glomerular filtration rate → ↓ level of erythropoietin → lower production of RBC in bone marrow → anemia  

Hydronephrosis is a condition where one or both kidneys become stretched and swollen as the result of a build-up of urine inside them.

Hydronephrosis is swelling of one or both kidneys. Kidney swelling happens when urine can't drain from a kidney and builds up in the kidney as a result. This can occur from a blockage in the tubes that drain urine from the kidneys (ureters) or from an anatomical defect that doesn't allow urine to drain properly.

Complete or partial unilateral/bilateral hydronephrosis

Distention (расширение) of the collecting system and renal capsule → pain;

Kidney stone lodge in the ureter→acute supravesical obstruction→severe pain;

Partial bilateral obstruction of urinary tract (kidney+ureter) → inability to concentrate urine → polyuria, nocturia

Obstruction of urinary tract → decreased Glomerular filtration rate (GFR) → renin secretion ↑ → ↑ blood pressure (hypertension) (more common in unilateral obstruction)

Hydronephrosis doesn't always cause symptoms. When they occur, signs and symptoms of hydronephrosis might include:

• Pain in the side and back that may travel to the lower abdomen or groin
• Urinary problems, such as pain with urination or feeling an urgent or frequent need to urinate
• Nausea and vomiting
• Fever
• Failure to thrive, in infants

Some common causes of hydronephrosis include:

• Partial blockage in the urinary tract. Urinary tract blockages often form where the kidney meets the ureter. Less commonly, blockages may occur where the ureter meets the bladder.
• Vesicoureteral reflux. Vesicoureteral reflux happens when urine flows backward through the ureter from the bladder up into the kidney. Typically, urine flows only one way in the ureter. Urine flowing the wrong way makes it difficult for the kidney to empty properly and causes the kidney to swell.

Hydronephrosis is usually treated by addressing the underlying disease or cause.

• Infections can be treated with antibiotics.
• A kidney stone can pass through by itself or might be severe enough to require removal with surgery.

In cases of severe blockage and hydronephrosis, excess urine may need to be removed using either a catheter to drain urine from the bladder or a special tube called a nephrostomy (see pic.) that drains urine from the kidney.