HCR 240: Nephrology and Urology

what is nephrology, urology, and another word for kidney

- nephrology: study of kidneys and kidney-related disease
- urology: study of bladder and bladder-related diseases
- the term renal may be used to refer to kidneys

where are the kidneys located and primary functions

- humans have 2 kidneys which are located in retroperitoneum
- primary functions of kidneys are to maintain optimal internal environments for tissue and cell metabolism

what is the functional unit of the kidney referred to as and its function

- the functional unit of the kidney is referred to as nephron
- nephron produces urine by filtering plasma through glomerulus → some substances may be reabsorbed or filtered through renal tubules → urine is then collected in calyces and renal pelvis to be transported to ureter

where does urine goes after being transported to ureter

urine then travels from ureter down to bladder → bladder has nonvoluntary internal urethral sphincter and a voluntary external urethral sphincter → distension of bladder triggers micturition reflex and relaxation of internal urethral sphincter (controlled by sympathetic and parasympathetic nerve fibers)

what is a urinary tract obstruction

- refers to the interference with the flow of urine at any site along the urinary tract
- onstructions can be further classified as upper urinary tract or lower urinary tract

what does severity of a urinary tract obstruction depend on

- cause of lesion
- duration of blockage (chronic or acute)
- location of blockage (closer to kidney is worse)
- degree of completeness
- whether it involves 1 or both urinary tract systems (unilateral or bilateral)

what is an upper urinary tract obstruction

- obstructions in upper urinary tract lead to increased hydrostatic pressure and dilation of ureter → renal pelvis → calyces → renal parenchyma → glomerulus
- this leads to reduced glomerulus filtration rate (GFR) and reflexive dilation of structures (hydroureter, hydronephrosis)

what are kidney stones

- most common cause of upper urinary tract obstruction is kidney stones
- also called renal calculi or urolithiasis
- kidney stones are masses of crystals, proteins, or mineral salts that form in urinary tract → the supersaturation of one or more salts lead to precipitation and then crystallization or aggregation into a stone

what are inhibitors of stone and crystal formation for kidney stones

pyrophosphate, potassium citrate, and magnesium

what are risk factors for kidney stones

- male gender
- inadequate fluid intake
- geographic location (high temperature/humidity)
- dietary patterns
- most people with kidney stones will develop their first stones before 50

what are clinical manifestations and treatment for kidney stones

- clinical manifestations: renal pain and signs/symptoms of urinary tract obstruction
- treatment:
→ pain management
→ smaller stones may pass without treatment
→ larger stones may require lithotripsy (shockwaves or laser to externally break down stone into smaller pieces)
→ stones that lead to complications like renal failure or obstruction may require surgical removal

what is a lower urinary tract obstruction

- relates to the ability of the bladder to empty into bladder outlet
- different causes of lower urinary tract obstruction include: neurogenic bladder, urethral stricture, and benign prostate hypertrophy

what are the different causes of a lower urinary tract obstruction

- neurogenic bladder: (cant pee/release urine) can be caused by lesions in brain or spinal cord that lead to loss of coordinated neuromuscular contraction
- urethral stricture: infection, surgery, or injury leads to narrowing of urethra
- benign prostate hypertrophy: most common cause in men; enlargement of prostate leads to obstruction of bladder outlet

what are renal tumors

- renal adenomas: benign solid tumors of the renal cortex which can transform into malignant tumors
- renal cell carcinoma (on inside): adenocarcinomas from tubular epithelial cells

describe renal cell carcinoma in renal tumors (risk factor, clinical manifestation, treatment)

- most common malignant renal cancer
- risk factors: male gender, smoking, obesity, hypertension, and renal failure
- clinical manifestation: hematuria (blood in urine), dull and aching flak pain, palpable flank mass in thinner individuals
- treatment:
→ localized disease: surgical removal of affected kidney (radical nephrectomy) or partial nephron-sparing nephrectomy for smaller tumors
→ combination of surgery, chemotherapy, radiation

what are bladder tumors (risk factor, clinical manifestations, treatment)

- urothelial carcinoma: cancer of uroepithelial cells of the inner lining of the ureters, bladder, and urethra
- risk factor: smoking, aromatic amines, arsenic in drinking water 
- clinical manifestations: gross (visible to eye) hematuria which may be episodic and accompanied by other nonspecific urinary tract symptoms like dysuria (pain while urinating), urgency, incontinence
- treatment: combination surgery, radiation, chemotherapy

what is a urinary tract infection, most common type, and common pathogen

- infection of urinary tract; may affect urethra, bladder, ureters, or kidneys
- most common type of UTI is cystitis, or inflammation/infection of bladder
- typically caused by genitourinary bacterial flora which overgrows or travel backwards into host’s body → common pathogens = E. coli and Staph saprophyticus

what are risk factors for a urinary tract infection

- premature newborns
- sexually active and pregnant women
- women who are on certain antibiotics
- patients with indwelling urinary catheters
- patients with diabetes mellitus

what are clinical manifestations of urinary tract infection

- some individuals with mild cystitis may be asymptomatic 
- common symptoms include frequency, urgency, dysuria (pain while urinating), hematuria, and/or cloudy foul-smelling urine, flank pain

how do you evaluate and treat a urinary tract infection

- evaluate: urine culture of specific microorganisms with counts of 10,000/mL or more
- treatment: antimicrobial therapy

what is pyelonephritis

- infection of upper urinary tract system (ureters, renal pelvis, kidneys) (*looks similar to UTI but more systemic symptoms)
- risk factor: female gender, kidney stones, vesicoureteral reflux (urine going backwards), pregnancy, neurogenic bladder, instrumentation, and sexual trauma

what are clinical manifestations and treatment for pyelonephritis

- clinical manifestations: acute onset of systemic symptoms (fever and chills). may have costovertebral angle tenderness (touching spot of kidney will hurt)
- treatment: antimicrobial therapy (typically more intense and longer than cystitis/UTI)

what is acute glomerulonephritis

- inflammation of glomerulus
- may be caused by immunological responses, ischemic injury, free radicals, drugs, toxins, infections, or as a consequence of chronic diseases like diabetes or lupus
→ immunological responses are most often immune complex mediated (type III hypersensitivity) but may also be type II or IV

what does acute glomerulonephritis lead to

- leads to decreased glomerular filtration rate (GFR) due to decreased blood flow and scarring
- increase in filtration pore size leads to loss of proteins, WBC, and RBCs in urine
- treatment: supportive care; find and treat underlying cause

what are clinical manifestations of acute glomerulonephritis

- frothy brown-tinged urine (cola-colored) from hematuria and proteinuria 
- low serum albumin due to loss in urine
- edema caused by decreased intravascular oncotic pressure
- severe or progressive glomerular disease can lead to eventual oliguria (urine output <30)

what is chronic glumerulonephritis

- if left untreated, acute glomerulonephritis can become chronic and eventually lead to chronic kidney disease (if its acute and you treat, it goes away; if its chronic it is permanent)
- most commonly chronic glomerulonephritis is due to secondary causes like diabetes or lupus
- injury to glomeruli can also lead to nephritic and nephrotic syndromes

what is renal failure

- develops once kidney function becomes impaired (anytime kidney is not doing its job)
- typically measured by certain factors like serum creatinine levels, glomerular filtration rate (GFR - higher value is better), and albuminuria

what can renal failure be categorized as

- acute (sudden onset; may be temporary or irreversible depending on underlying cause)
- chronic (progressive renal failure typically caused systemic disease process)

what is renal insufficiency, renal failure, and end stage renal disease in renal failure

- renal insufficiency: renal function reduced by 25%
- renal failure: renal function reduced significantly
- end stage renal disease: less than 10% of renal function remains

what is acute kidney injury (AKI)

- sudden decline in kidney function
- clinical measured by decreased GFR, increased serum creatinine, increased blood urea nitrogen (BUN - toxic), and reduced urine output
- causes of AKI can be divided into 3 main categories: pre-renal, intrarenal, post-renal

what is the pre-renal cause of acute kidney injury

- inadequate renal perfusion leads to eventual decrease in glomerular filtration pressure (problem with blood flow)
- ex: hypotension of any cause, hypovolemia from acute blood loss/hemorrhage, renal vasoconstriction caused by NSAIDs (ibuprofen)

what is the intrarenal cause of acute kidney injury

- direct injury of renal parenchyma or interstitial cells (kidney itself is injured and you directly injured kidney)
- ex: acute tubular necrosis, exposure to nephrotoxic contrast dye, acute glomerulonephritis, graft rejection, rhabdomyolysis

what is the post-renal cause of acute kidney injury

- urinary tract obstruction leads to increased intratubular pressure and decreased GFR (problem with flow of urine/blockage)
- ex: tumors, kidney stones, neurogenic bladder

what are clinical manifestations of acute kidney injury (AKI)

- fatigue, nausea, vomiting
- oliguria: reduced urine output of less than 30ml/hour
- anuria: severely reduced urine output of less than 10ml/hour or complete absence of urine production
- electrolyte disturbances: hyperkalemia and hyperphosphatemia
- metabolic acidosis: secondary to hyperkalemia
- decreased GFR, elevated BUN and creatinine

how do you prevent and treat acute kidney injury

- prevention: maintenance of fluid volume before and after surgery/diagnostic procedures when nephrotoxic drugs or contrast agents are used
- treatment: supportive care (correct fluid and electrolyte disturbances, normal blood pressure levels, prevent/treat infections, adequate nutrition, avoid nephrotoxic meds)
→ if reversible, recovery may take up to a year

what is chronic kidney disease (CKD)

- progressive loss of renal function; typically caused by underlying systemic diseases like uncontrolled hypertension, diabetes, systemic lupus erythematous, or intrinsic kidney disease
- can be measured by decreased GFR, increased serum creatinine, increased blood urea nitrogen (BUN), degree of albuminuria, reduced urine output

what are factors that contribute to chronic kidney disease

- proteinuria contributes to tubulointerstitial injury by promoting inflammation and progressive fibrosis → peeing out proteins - proteins do not belong in urine so when we pee out protein, it is slipping through glomerulus and entering renal tubules. the proteins are banging against walls of renal tubules and damages it, causing injury/inflammation
- angiotensin II promotes glomeruli hypertension which may progress to tubulointerstitial fibrosis and scarring → renin-angiotension-aldosterone pathway

what is the renin-angiotensin-aldosterone pathway

liver secretes angiotensinogen that does not do anything and just sits in blood → if kidney recognize that blood flow is low, it will secrete renin and renin will activate angiotensinogen into angiotensin I → angiotensin I will travel to lungs where there is angiotensin converting enzyme and it will cleave angiotensin I into angiotensin II → angiotensin II causes vasoconstriction

what are clinical manifestations of chronic kidney disease

- similar to AKI but they do not appear until after 25% of renal function is lost
- can develop life-threatening hyperuremic syndrome (deadly, can cause heart failure, happens when BUN gets too high) → toxic build up of end-products of metabolism leading to hypertension, anorexia, nausea/vomiting, diarrhea, constipation, malnutrition, weight loss, seizures, cardiovascular disease

what are other considerations in CKD in regards to fluids, potassium/phosphate, and metabolism

- edema and fluid overload → need careful balance of salt/water intake in diet, too much fluid = pulmonary edema and dyspnea, weight gain
- decreased urinary excretion of potassium and phosphate lead to electrolyte disturbances → high potassium = life threatening cardiac irregularities, metabolic acidosis, low levels of calcium (chvostek and trousseau sign)
- patient develops altered protein, carbohydrate, and fat metabolism → nausea and vomiting = malnutrition and weight loss, associated with glucose intolerance and dyslipidemia 

what are other considerations of CKD in regards to cardiovascular considerations

- cardiovascular abnormalities are more common in patients with CKD → hypertension, glucose intolerance, inflammation, potassium abnormalities can lead to increase cardiovascular risk

what are other considerations of CKD in regards to hematological considerations

- kidneys are responsible for producing erythropoietin to stimulate new production of RBCs; failing kidneys means less or no erythropoietin and development of anemia
- loss of protein leads to loss of plasma proteins including coagulation cascade, patient is more prone to bleeding
- loss of plasma proteins including complement cascade; patient will be more likely to develop infections

how do you treat patients who no longer have functioning kidneys

- hemodialysis: machine takes your blood and removes toxins
- peritoneal dialysis
- kidney transplant: old kidneys are left in place (except with renal carcinoma) and new kidneys come from alive or dead patients and placed in lower abdomen near pelvis 

what are anatomical renal abnormalities of congenital abnormalities

- ectopic kidney: kidneys fail to ascend into abdomen from pelvis (kidney is in wrong place)
- horseshoe kidney: kidney fuse in middle of abdomen as they ascend (kidney fuses together in middle)
- renal agenesis: absence of one or both kidneys; remaining kidney is typically normal but becomes hypertrophic and prone to developing CKD due to increased stress on an organ

what are anatomical urinary tract abnormalities of congenital abnormalities

- vesicoureteral reflux: malfunctioning valve allows backwards flow of urine; common presenting symptoms are frequent UTIs
- congenital bladder outlet obstructions (not peeing - bad)

what is hemolytic uremic syndrome (HUS) - (pediatric nephrological diseases)

- acute disorder characterized by hemolytic anemia, thrombocytopenia, and renal impairment (similar to DIC but not as bad/severe)
- most common community-acquired cause of acute renal failure in children
- associated with bacterial and viral endotoxin agents (esp E. coli)

describe bacterial and viral endotoxin agents in hemolytic uremic syndrome (HUS) - (pediatric nephrological diseases)

- bacterial toxin causes lysis of RBCs and activation of caogulation cascade and platelets
- toxin also travels to kidneys where it causes lysis of endothelial basement membrane cells of glomeruli
- arterioles of glomerulus become swollen and occluded with fibrin clots
→ this leads to further destruction of RBCs as they pass through the swollen glomeruli blood vessels

what are clinical manifestations for hemolytic uremic syndrome (HUS) - (pediatric nephrological diseases)

- classic triad: anemia, thrombocytopenia, and AKI (most will recover)
- classic presentation is prodromal gastrointestinal illness with diarrhea followed by sudden onset of severe HUS symptoms 1-2 weeks later
→ HUS symptoms include anemia due to destruction of RBC
→ stimulation of platelets leads to microthrombi while overuse and depletion of coagulation plasma protein leads to easy bruising, purpura, and bloody diarrhea
→ acute renal failure symptoms like volume overload, oliguria, hypertension, metabolic acidosis, hyperkalemia

what is a willis tumor - (pediatric nephrological diseases)

- malignant embryonal tumor of kidney also known as nephroblastoma
- most common solid tumor of childhood → peak incident is 2-3 years of age
- can develop sporadically or from genetic inheritance

what is the two-hit hypothesis of willis tumor - (pediatric nephrological diseases)

- willis tumor-suppressor genes WT1 and WT2 are located on chromosome 11
- children who inherit a mutation in one allele of a tumor-suppression gene require just one more somatic mutation for a tumor to form
(*you need both of these to happen for willis tumor)

what are clinical manifestations and treatment for a willis tumor - (pediatric nephrological diseases)

- most common presentation is an enlarging asymptomatic upper abdominal mass in a healthy, thriving child (presenting symptoms is nothing so if u feel something its abnormal)
- as mass grows, child may experience vague abdominal pain, hematuria, fever, and hypertension
- treatment: cancer staging for prognosis and treatment - surgery, chemotherapy, radiation