If one advances confidently in the direction of his dreams, he will meet with a success unexpected in common hours

--Henry David Thoreau

"Shoot for the moon. Even if you miss it, you will land among the stars.!"
- Les Brown

Pathology of Hypertension:
Dr. Venkatesh M. Shashidhar.
Associate Professor of Pathology Fiji School of Medicine

Hypertension - Introduction
Silent Killer painless complications dizziness, headache, and visual difficulties, It is the leading risk factor MI, DM, Stroke 25% of population, <35% unaware. <5% ..!

Introduction
Complications bring to diagnosis but late Sustained increase in blood pressure Systolic >140, Diastolic > 90 mm of Hg*

Control of Blood Pressure:

Vasoconstrictors Angiotensin II Catecholamines Humoral Factors Vasodilators Pg & Kinins

Blood Volume Na+, Aldosterone

BP
Cardiac Factors Rate & Contract..

Cardiac Output

Peripheral Resistance
Local Factors pH, Hypoxia

Neural Factors Adrenergic Cons Adrenergic - Dil

Etiologic Classification:
Primary or Essential Hypertension(95%) Secondary Hypertension (5-10%)
Renal Kidney disorders. Other endocrine, drugs etc.

Pathogenesis of complications Of Hypertension

Ishchemia MI, CNS, Kidney, eye
Aneurism / Rupture CNS, Aorta,

Myocardial Hypertrophy LVH, Cardiac failure.

Consequences of Hypertension:
Blood Vessels Atherosclerosis, Arteriolosclerosis. Heart Enlarge, Ischemia, Infarction. Kidney Ischemia, Infarction - nephrosclerosis. Eyes: Retinopathy Ischemia, infarction. Brain: Ischemia, infarction, Haemorrhages.

Thickening of blood vessel:

Narrow Lumen

Onion Skin Thickening Of arterioles.

Hypertrophy of heart:

Left Ventricular Hypertrophy

Brain Haemorrhage:
Cerebral Blood vessels Special features: Thin walled* End arteries* Cong. Aneurisms

Cerebral Infarction (Stroke) :

Haemorrhagic Necrosis

Cerebral Infarction:

Kidney damage Benign Nephrosclerosis:

Leathery Granularity due to minute scarring

Risk Factors for Atherosclerosis:

Hypertension Hyperplastic A. sclerosis Diabetes Hyaline A. sclerosis Smoking Endothelial damage. Hypercholesterol Endothelial damamge Life style, lack of exercise, stress, obesity.

All factors damaging Blood vessels predispose to development of atherosclerosis.

Normal Retina - Fundoscopy

Hypertensive Retinopathy:

Conclusions:
Persistent increased blood pressure (140/90) 95% Essential, 5% secondary - Renovascular Benign and Malignant types (>120Diastolic) Vessel damage & Arteriolosclerosis Complicates - Atherosclerosis, Diabetes, IHD Ischemia or Infarction in end organs. Kidney, Brain, Heart & Eyes. Nephrosclerosis, renal damage, IHD, MI, Stroke & Retinopathy.

Pathology of Diabetes

Dr. Venkatesh M. Shashidhar Senior Lecturer in Pathology Fiji School of Medicine

Diabetes Mellitus
Disorder of metabolism (Carb, Prot & Fat) Due to Absolute or relative deficiency of insulin. Characterized by hyperglycemia. Clinically : Polyuria, Polydypsia, Polyphagia.

Classification
Primary DM.
Type I IDDM / Juvenile 10%. Type II NIDDM /Adult onset 80%. MODY 5% maturity onset - young - Genetic

Secondary DM islet destruction.

Infectious congenital rubella, CMV. Pancreatitis/tumors/Hemochromatosis. Endocrinopathy, gestational DM, downs. Drugs Corticosteroids.

Pathogenesis of Type I DM
Genetic HLA-DR3/DR4 Environment ? Viral infe..??

Autoimmune Insulitis cell Destruction Severe Insulin deficiency

Type I DM

Pathogenesis of Type II DM
cell defect Genetic Abnormal Secretion Environment Obesity ??? Insulin resistance

Relative Insulin Def.

cell exhaustion

Type II DM

IDDM

Complications:
Short term Complications: (metabolic)
Hypoglycemia Diabetic Ketoacidosis Non Ketotic hyperosmolar diabetic coma Lactic acidosis

Long term Complications:(microangiopathy)

Angiopathy, Retinopathy, Nephropathy, Neurophathy

Long term Complications:

Angiopathy
Atherosclerosis Hyaline arteriolosclerosis Diabetic microangiopathy

Nephropathy
Nodular glomerulosclerosis

Retinopathy
Non Proliferative & Proliferative

Neuropathy
Peripheral axonal neuropathy

Pathogenesis of Microangiopathy:
1. Long standing diabetes 2. Glycosylation of BV proteins. 3. Protein deposits in the BM.

4. Thick and Leaky blood vessels

5. Exudation & Ischemia

6. End Organ damage...

Diabetic Micro-angiopathy is the primary cause of diabetic pathies

(hyaline arteriolosclerosis)

Infections in Diabetes:
Blood vessel damage ischemia Decreased intracellular glucose - defence Glycosylation of inflammatory mediators Glycosylation of immunoglobulins Lastly increased glucose in blood.

*** Not just due to increased glucose.!

Microangiopathy

Pathogenesis of Complications

Atheroma Coronary Artery:

Diabetic Gangrene

Normal Retina

Diabetic Retinopathy
Cotton wool spots

Pathogenesis of Nephropathy

Diabetic Glomerulosclerosis

Laboratory Diagnosis:
Urine glucose - dip-stick Screening Random or fasting blood glucose (<11) Fasting > 7mmol, Random >11mmol If Fasting level is between 7-11 then OGTT HbA1c - for follow-up, not for diagnosis Fructosamine - for long term maintenance.

Take home points:

Type-I Young, Acute Metabolic complications - Ketoacidosis. Type-II - Chronic Vascular complications
Microangiopathy Kidney,Retina,Brain, BV.

Hypoglycemia is more dangerous.

Take home points:

Duration & level of hyperglycemia are directly proportional to Chronic (Vascular) complications. Infections are due to microangiopathy and ischemia, immuno suppression and lastly hyperglycemia.