Pathophysiology of Diabetes Mellitus Type II

Precipitating factors:

1. development of glucose intolerance during drug therapy

2. GDM3. sedentary lifestyle4. stress5. obesity6. decrease serum potassium7. Toxin/Virus

Predisposing factors:

1. family history of DM/Genetic2. Age above 403. Race4. Gender

Idiopathic

Insufficient insulin-receptor on the insulin-dependent cells (liver

cells, muscles and fats)

Impaired beta cell function and insulin secretion

Reduced hepatic insulin sensitivity

Body does not respond to the action of insulin (Insulin

Resistance)

Decreased insulin production

Reduced tissue uptake of glucose

Liver senses low glucose level

Liver converts Glycogen to glucose

and releasing it to the Blood

A B

Acidity of urine Urethral flora

UTI VaginitisTreatment:

Medications:-Metronidazole-Azithromycin-Diflucan-Doxycycline

Treatment:

Medications:

-Amoxicillin

-Nitrofurantoin

-Ciprofloxacin

-Quinolones

C

Decreased transportation and use of glucose

↑ Insulin demand

Insulin response by beta cells declines d/t exhaustion

Blood glucose level rise: Initial Stage

S/Sx:

Hyperglycemia (>120 mg/dl)

Blood glucose > renal threshold

↓reabsorbtion capacity of the renal tubules

Excess glucose spills into the urine

High blood glucose draw water

from the cell

S/Sx:glucosuria

↑ Osmotic pressure in the filtrate

S/Sx:PolyuriaElectrolyte imbalance

Large volume of urine to be excreted

Fluid loss

Dehydration

S/Sx:polydipsia

Treatment:

Insulin Administration

Fluid & electrolytes

Continuous Decreased transportation of glucose and

nutrients into the cells

Stimulation of hunger mechanism via hypothalamus

Stimulation of appetite

S/Sx:polyphagia

If Treated:

Insulin therapy or Hypoglycemic agent

Exercise Reduction of

stress Diet

FAIR PROGNOSIS

A

B

C

D E

Severe hypoglycemia

If insulin rise due to many factors

Excess insulin transports glucose into cells

Increase gluconeogensis

SNS stimulation

Decreased CNS function

Glucose intake Insulin stores excess glucose in

the Blood

Blood glucose decrease

Return to stable state

Relative insulin deficit

Hyperosmotic plasma

Severe dehydration of cells

Hyperosmolar Hyperglycemic Nonnketotic

Syndrome(HHNS)

Coma

Death

Cells convert fats into glycerol and fatty acids for energy

Fatty Acids accumulate in the Liver

Fatty Acids are converted to Ketones: hydroxybutyric

acid, acetoacetic acid, acetone

Glucose available for brain drops

Some ketoacids excreted in the urine

ketoacidosis

S/Sx:

ketonuria

Ketone acids associate to yield hydrogen ions

Decrease in pH

Metabolic acidosis

S/Sx: Acetone Breath

F

I

J

If poor compliance

Insulin deficit severe/prolonged:

Damage of small blood vessels

Development of microaneurysms in the

capillary walls

Development of microaneurysms in the

capillary walls

Shifting of fluid in the interstitial spaces

Hard exudate formation

Tearing, partial or complete retinal

detachment

Atrophy of new vessels and contractions

Transitory lens change

Opacity of the lens

Neovascularization

New vessels formed are fragile causing hemorrhage and

contractures of the vitreous and pulling of

retina

S/Sx:

Blurring of vision

Decrease color perception

S/Sx:

Dark red circular spots

Sorbitol accumulation in the nerve cells

Damage on the Schwann cells

Diabetic Neuropathy

Impaired peripheral and central vision

Blindness

D E

F

G

KO

Increased blood viscosity

Sluggish circulationBlood pooling at left ventricle

Left ventricle hypertrophy

Imitation of endothelial lining of the blood

vessels

Blood Stasis

Shunting of glucose in polyol pathway

Enzyme system converts glucose to sorbitol and slowly to

fructose in an attempt to normalize the glucose level

Accumulation of sorbitol in the basement membrane of the cell and between that uses sorbitol

pathway

Basement membrane thickening

Poorly controlled glucose

Ischemia

myocardial infarction

Thrombus Formation

Heart

Cerebrovascular Accident(Stroke)

Brain

Decrease blood flow to the periphery(big vessels)

Delayed wound healing

ischemia

necrosis

gangrene

The cell receives inadequate oxygen and nutrition and retained waste products

Decreased blood flow in small vessels S/Sx:

Ulceration Diabetic

foot

Treatment:

debridementamputation

G

K

L

Neurons unable to store glucose

Energy Crisis

Hypoglycemic shock

Neurons cannot function

DEATH

coma

Lung exhaustion

Failure of respiratory buffer system

Rise in carbonic acid

Further decrease in the pH level, hyperosmolality, hypotension, tissue damage, depression of

central function

Coma

Death

pH compensation; Kussmaul respirationABG: Decreased PaCO2

I

J

Associated Complications

as a result

of DM together with CRF

Accumulation of fats and toxic substances in the liver as a result of DM and CRF

Liver necrosis

Fibrosis and scarring

glucose

Liver inflammation

Bile saltLipoprotein cholesterol

Hyper bilirubenemia

Steroid hormones

bilirubnDrug interaction/t

oxicities

Amino acidsproteins bilirubin

hypoalbuminemia Decreased coagulation factors

Dec. cholesterol

Impaired fat absorption

Impaired conver-sion of ammonia to urea

Hepatic encephalo-pathy

Increased aldosterone

Disorders of synthesis and storage functions

Disorders of metabolic and excretory functions

Increased androgen, estrogen

S/Sx:

Hypoglyce-mic

S/Sx:Edema/ascites

S/Sx:bleeding

S/SDef. of fat-soluble vitamins

S/Sx:Fatty stools

S/Sx:Asterixis, confusion, coma

S/Sx:edema, ascite

S/Sx:Menstrual irregularities

S/SxJaundice, ictieric sclera, clay-colored

stool

drugs

Decreased renal blood

flow

Nodular glomerulosclerosis

(inter-capillary glumerulosclerosis

Diffuse glomerular sclerosis (mesangial

matrix)

Progressive loss of kidney function

Acute Renal Failure

Initiation Stage

Maintenance Stage

Slow progress characterized by irreversible reduction in

GFR

Loss of nephrons

S/S:

Oliguria Scanty

output Hematuria Decrease

urine

Management:

Maintenance of body fluids

Hemodialysis Peritoneal

Dialysis Medicatrtions Nutritional

Therapy

Nephropathy

L

M

Fibrosis and scarring

Portal hypertension

Inc. pressure in peritoneal cavities

Portosystemic shunting of blood

splenomegaly

Shunting of ammonia and toxins into circulation

Development of collateral channels

S/Sx:

ascites

S/Sx:HemorrhoidsEsophageal varices

Hepatic encephalopathy

S/Sx:

asterixis

S/Sx:Anemia, thrombocytopenia

Stage 1

Decreased Renal Reserve

No symptoms:

Residual Reserve 40%

Further loss of nephron function

Stage 2

Renal Insufficiency

S/S:

Mild azotemia Mild anemia GFR decrease to 20

mL/min Residual renal function

15-20%

No homeostasis;

symptomatic in many systems;

5 % residual renal function

Loss of excretory renal function

Stage 3Renal Failure

Decreased excretion of nitrogenous waste

Uremia

Stage 4End Stage Renal Disease (ESRD)

Chronic Kidney Disease

S/S:

Severe azotemia

Severe anemia Nocturia 5-15% residual

renal function

M

N

Excess pronucleating factor

(Mucin and Non-mucin glycoprotein)

Deficiency of antinucleating factor (apolipoproteins AI &

AII)

Cholesterol monohydrate crystal nucleation and crystal growth within mucin gel layer

Unstable cholesterol-rich vesicle remain

Vesicle fusion

Liquid Crystals

Continued growth of the crystals by direct nucleation of cholesterol molecules from supersaturated unilamellar or multilamellar biliary vesicles

Biliary sludge

SUPERSATURATION OF BILE WITH CHOLESTEROLSupersaturation of

cholesterol is a necessary but not

sufficient condition for the formation of

gallstone

Gallstone formation:

CHOLECYSTOLITHIASIS

Silent/ Asymptomatic gallstones

If Treated:

• Nutritional and supportive Therapy

•Pharmacologic Therapy

• T-tube Tract

•Extracorporeal Shockwave Lithotripsy

•Intracorporeal Lithotripsy

•Cholecystectomy

FAIR

R

O

G

N

O

S

I

If not treated

Small Stones pass into CBD

<5mm

Obstruction of Bile Flow on

CBD

Larger stones obstruct bile flow

on the Gallbladder

CHOLEDOCHOLITHIASIS

Gallbladder Distention

Migrate in the extra hepatic biliary tree through cystic duct

MIZZIRI’S SYNDROME

Increase Intraluminal pressure

(Mechanical inflammation)

Release of lysolecithin and other tissue local

factors(Chemical inflammation)

Bacterial Inflammation

Erodes lining of Gallbladder

Erodes lining of CBD

S/S:

• Asymptomatic gallstonesOr

• Follows acute cholecystitis

If Treated:

Hemodialysis Peritoneal

Dialysis Pharmacologic

Therapy Nutritional

Therapy Kidney

Transplant

Fair prognosis

If Not Treated

Hematologic:

Anemia Bleeding Infection

Musculoskeletal:

Retarded growth Renal

osteodystrophy

Cardiovascular:

Increase Blood Pressure

Congestive Heart Failure

Pericarditis

Neurologic:

Peripheral neuropathy

Uremic encephalopathy

Neurologic:

Peripheral neuropathy

Uremic encephalopathy

Multi-system Failure

Death

N

O

PHERIPHERAL NEUROPATHY

AUTONOMIC NEUROPATHY

PROXIMAL NEUROPATHY

FOCAL NEUROPATHY

numbness or insensitivity to pain or temperature

a tingling, burning, or prickling sensation

sharp pains or cramps extreme sensitivity to

touch, even light touch loss of balance and

coordination

HEART GASTRO-INTESTINAL

Urinary Tract & Sex Organs

Sweat Glands

EYES

Sharp Decrease in Blood Pressure

Increased Heart rate Constipation

Gastroparesis Nausea and

Vomiting Loss of Apetite

GASTROPATHY Urine retention Impotence

Profuse sweating at night or during eating

Sluggish pupils Cannot see well

when there is sudden change in light

Pain in thighs, hips, buttocks, or legs

Weakness of legs

Inability to focus the eye

Double vision Aching behind

one eye Paralysis on one

side of Face( Bell’s Palsy)

Severe pain on lower back

Pain in chest, abdomen, foot