Pathophysiology

PHCL 415

• Lecturer: Haya M. Al-Malaq, Msc- course co-ordenator.

• Lecturer: Rania Al-Jaizani, Msc

Contact info• E-mail: haya_malak@yahoo.com

Grade distribution • Mid 1 -25• Mid 2 -25• Assignment 10• Final 40

Text book• Price SA, Pathophysiology, clinical concept of

disease process, Fifth edition.• Zdanowicz MM, Essentials of pathophysiology

for pharmacy.• Handouts for anatomy part.

Part 1Renal System Disorders

Lecture 1• Introduction • Anatomy & physiology of renal system• Major functions of the kidney• Manifestation of renal disorders• Diagnosis • UTI• NB

Introduction • The kidneys are vital organs that play a critical role

in the maintenance of stable internal environment.• The kidneys regulate fluid and electrolyte and acid

base balance of the body and excrete metabolic wast products and foreign chemicals.

• When the kidneys fail to perform vital functions a condition known as uremia or ESRD results and this require dialysis or death may occur within 3-4 wks.

Introduction • ESRD is a major cause of morbidity and

mortality.

Medical encyclopedia- Medline plus

Anatomy of Urinary tract • The kidneys are bean shaped organs situated

on both sides of the vertebral column.• The rt kidney are slightly lower than left b/c it

is bushed down by the liver.• The 2 ureters are tubes 10-12 inc long

extending from the kidneys to the bladder, their only function is to convey urine to the bladder.

Anatomy of Urinary tract• The bladder is a collapsible muscle bag with 3

openings (2 ureters, 1 urethra).• The bladder has 2 basic functions: 1) reservoir

for urine, 2) expels urine from the body.• The kidney is protected from direct trauma by

the ribs and intestine.

Microscopic structures of the kidney

• Nephron: functional unit of the kidney, 1000 000 in each one, we can survive with onley 20 000

• Renal corpusle: bowmans capsule and the glumarular capillary tuft

• Juxtaglomerular apparatus: produce renin

Functions of the kidneys

Excretory function • Maintain plasma osmolality near 285 mosm by varying

the excretion of water.• Maintain ECF volume and BP by varying excretion of Na+• Maintain the plasma conc of each electrolyte within

normal range• Maintain plasma PH near 7.4 by eliminating xs H+ and

regenerating HCO3-• Excrete the nitrogenous end product of protein

metabolism (urea, UA, Cr)• Serves as excretory route for most drugs

Non-excretory functions • Synthesis and activate hormones:• Renin: BP• Erythropoietin: RBCs from BM• Vit D: hydroxylation of Vit D to its vital form• PG: vasodilator acts locally and protect from

renal ischemia• Degradation of polypeptide hormones (insulin,

glucagon, GH, prolactin, ADH, parathormon, GI hormones)

Basic renal physiology• Glomerular ultrafiltration• Autoregulation of renal plasma flow and GFR• Tubular reabsorption and secretion• Regulation of water balance• Regulation of body Na

Glomerular ultrafiltration• Renal blood flow 25% of cardiac output• GFR: 125ml/min• Passive process• Same as plasma but with no protien• Charge selective, size selective

Autoregulation of renal plasma flow and GFR

• RPF and GFR kept constant through the day• 1) myogenic strech receptor, 2)

tubuloglomerular feed back.• Hormones: NE, angio II, PG

Tubular reabsorption and secretion• Electrolytes (Na, K, Ca, Mg, Cl, HCO, HPO) &

non electrolytes (glucose, Cr, Ua) are filtered.• Most of filtered substance are reabsorbed

through minute pores in the tubules and some substance are secreted.

• Active passive transport mechanism.

Regulation of water balance• High water intake >>>>>>> diluted urine• Low water intake >>>>>>>> conc urine

Regulation of body Na• Renin-angiotensin-aldosterone system

Diagnostic procedure in renal disease

Diagnosis

Biochemicalmethod

Chemical examination GFR

Morphologic method

Microscopicexam

Bacterialogic exam

Radiologic exam

Renal biopsy

Manifestations of renal disease Characteristic Abnormality

Appearance Color

OdorSps gr Protein Glucose, ketonsRBCsEpithelial cellsBacteriaOval fat bodies Casts Crystals

Cloudy (renal disease)Red or brown (hematourea) renal dis or jandeceUnplesent in UTILo in RFMost renal diseaseDMUTI, nephritis, neoplasm, stoneRenal diseaseUTINephrotic syndrumRenal diseaseAbnormal aminoacidurea

UTI

Introduction • A urinary tract infection (UTI) is a

bacterial infection that affects any part of the urinary tract.

• Although urine contains a variety of fluids, salts, and waste products, it usually does not have bacteria in it.

• When bacteria get into the bladder or kidney and multiply in the urine, they cause a UTI.

Types • The most common type of UTI is a bladder

infection which is also often called cystitis. • Another kind of UTI is a kidney infection,

known as pyelonephritis, and is much more serious.

• Complicated, uncomplicated, recurrent.

Most common• DM, SCA.• Female (short urethra, absence of prostate, near the

annus).• Poor toilet habits.• Pregnancy and prostatits. • Allergy• Urinary catheter• Prostatic stent• Sexual intercourse• Elderly.

Treatment • Appropriate antibiotic• Surgical correction of obstruction or structural

abnormality that might be causing urine retention

Neurogenic bladder

Introduction • Neurogenic bladder refers to dysfunction of

the urinary bladder due to disease of the central nervous system or peripheral nerves involved in the control of micturition.

Introduction • The bladder is a distensible reservoir for urine

from which the urine is evacuated at suitable intervals. The innervation of the bladder consist of reflex arc at the S1 & S4 level of the spinal cord, whose function is modified by sensory & motor connections to higher centers in the brain.

• Interference of efferent or afferent limbs of the reflex arc can disrupt normal micturition; this condition is referred to as neurogenic bladder.

Causes • Neurogenic bladder is often associated

with spinal cord diseases, injuries, and neural tube defects including spina bifida.

• It may also be caused by brain tumours & other diseases of the brain, & by peripheral nerve diseases.

• It is a common complication of major surgery in the pelvis, such as for removal of sacrococcygeal teratoma & other tumours.

Types • Uninhibited NB• Reflex NB• Autonomus NB• Sensory paralytic NB• Motor paralytic NB

Uninhibited NB• Defect in corticoregulatory tract.• Lesions that involves cerebral cortex.• The patient is aware of sudden desire to

urinate as the bladder fills but maybe unable to inhibit the desire to void even though the situation may not be appropriate.

Reflex NB• Occurs in spinal cord injury above S2 level.• All bladder sensation is lost.• Empting occur reflexly whenever there is

pressure.• Emptying is incomplete b/c lack of motor

input.

Autonomus NB• Destruction of both limps of the bladder arc as

in surgery• Patient cannot initiate urination.• Manual pressure.

Sensory paralytic NB• Lesions in the sensory limb of the bladder

reflex arc (diabetic neuropathy, MS).• Gradual loss of bladder sensation.• Emptying is incomplete.

Motor paralytic NB• Involve motor nerve as in tumor• The sensation of bladder fullness is intact but

the patient cant initiate urination.• Patient may require catheterization.