Nutritional Diseases

Slide 1 · Nutritional Diseases

Mechanisms, morphology and clinicopathologic consequences

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Distinguish primary from secondary nutritional disorders and explain their pathogenesis.

Recognize protein–energy malnutrition and its tissue manifestations.

Link characteristic micronutrient deficits to their molecular functions.

Explain how excess adiposity and dietary patterns contribute to systemic disease.

Slide 3 · The nutritional disease spectrum

Insufficiency

Deficient intake or assimilation

Specific deficiency

Vitamins, minerals or trace elements

Excess adiposity

Energy homeostasis dysregulation

Systemic injury

Metabolic, vascular and neoplastic effects

Undernutrition and overnutrition are both causes of structural and functional disease.

Slide 4 · Three essential contributions of diet

Energy

Carbohydrate, fat and protein supply

Structural substrates

Amino acids and essential fatty acids

Regulatory nutrients

Vitamins, minerals and cofactors

Defects at any level can compromise growth, tissue maintenance and repair.

Slide 5 · Primary versus secondary malnutrition

Dimension

Primary

Secondary

Fundamental defect

Diet lacks required nutrients

Nutrients unavailable or inadequately utilized

Example

Food insecurity; Restricted intake

Malabsorption; Chronic illness

Physiologic problem

Insufficient supply

Impaired absorption, excess loss or increased need

Clinical implication

Restore adequate intake

Identify and address underlying disease

Slide 6 · Mechanisms producing nutrient deficiency

Low intake

Poverty, restricted diet

Low availability

Malabsorption or defective storage

High loss

Chronic gastrointestinal or renal loss

High demand

Growth, pregnancy or illness

These pathways may coexist in the same patient.

Slide 7 · Poverty and environmental disruption

Food insecurity may reflect limited access to protein, energy and micronutrient-rich foods.

Crop failure, drought, displacement and conflict amplify nutritional vulnerability.

Children, older adults and socially disadvantaged populations are particularly exposed.

Deficiency patterns reflect both food quantity and dietary diversity.

Slide 8 · Chronic disease promotes wasting

Underlying disease

Cancer, chronic lung or inflammatory disease

Inflammatory response

Cytokines and altered energy expenditure

Muscle proteolysis

Amino acids used for metabolism

Clinical phenotype

Weight loss and impaired recovery

Nutritional support alone may not fully reverse inflammation-driven catabolism.

Slide 9 · Excessive alcohol use and deficiency

Deficiency arises through poor diet, abnormal absorption, utilization and storage.

Thiamine, pyridoxine, folate and vitamin A deficiencies are emphasized.

Unrecognized thiamine depletion can lead to Wernicke encephalopathy and lasting neurologic injury.

Clinical evaluation should assess specific deficits, not only caloric intake.

Slide 10 · High-demand physiological states

Infancy and adolescence require nutrients for rapid tissue growth.

Pregnancy increases demands for selected nutrients and building blocks.

Failure to adjust dietary intake may produce clinically important deficiencies.

An apparently sufficient diet can become insufficient when needs change.

Slide 11 · Impaired absorption, storage or utilization

Gastrointestinal disorders may prevent absorption despite adequate dietary supply.

Certain genetic disorders or drug exposures interfere with nutrient use.

Chronic protein losses can produce a kwashiorkor-like phenotype.

MECHANISM MAP

Dietary availability

Intestinal absorption

Tissue transport / storage

Cellular use

Slide 12 · Common nutritional phenotypes

Phenotype

Dominant defect

Typical finding

Energy deficiency

Negative energy balance

Loss of fat and muscle

Protein-predominant deficit

Visceral protein depletion

Edema; Fatty liver

Micronutrient deficiency

Defective enzyme or tissue function

Specific organ syndromes

Obesity

Dysregulated adiposity

Metabolic and inflammatory injury

Slide 13 · Why infection worsens malnutrition

Low nutritional reserve

Defective immune responses

Intercurrent infection

Cytokines and increased demand

Further catabolism

Muscle and nutrient depletion

Clinical deterioration

More susceptibility to infection

Malnutrition and infection form a reinforcing pathogenic cycle.

Slide 14 · Clinical assessment of undernutrition

Anthropometric measures assess growth, body mass and tissue wasting.

Subcutaneous fat stores and muscle bulk document somatic depletion.

Edema may mask true weight loss, especially in kwashiorkor.

Serum proteins require interpretation in the context of inflammation and disease.

Slide 15 · Severe acute malnutrition: Textbook criteria

Criterion

Textbook threshold / observation

Mid-upper arm circumference

Less than 115 mm

Weight-for-height

More than 3 SD below reference median

Nutritional edema

Bilateral pitting edema of lower limbs

The source presents alternative criteria in young children; Not a substitute for a full clinical assessment.

Slide 16 · Wasting and stunting describe different patterns

Wasting reflects reduced tissue mass relative to linear growth.

Stunting reflects impaired longitudinal growth after sustained or early-life nutritional insult.

Maternal and early childhood malnutrition may contribute to stunting.

Acute and chronic nutritional disorders can occur together.

Slide 17 · Two functional protein compartments

Compartment

Main representative

Depletion most apparent in

Somatic

Skeletal muscle proteins

Marasmus

Visceral

Proteins of liver and visceral organs

Kwashiorkor

Assessment correlate

Muscle circumference / serum proteins

Patterns differ by phenotype

Slide 18 · Marasmus: Adaptive tissue catabolism

Severe calorie lack

Energy substrate shortage

Lipolysis

Subcutaneous adipose loss

Proteolysis

Skeletal muscle depletion

Wasting

Emaciation and growth failure

Visceral protein stores are relatively protected compared with somatic muscle.

Slide 19 · Marasmus: Clinical morphology

Marked loss of subcutaneous fat and skeletal muscle creates emaciated limbs.

The head may appear disproportionately large relative to the wasted body.

Growth failure, anemia and accompanying vitamin deficiencies are common.

Defective cell-mediated immunity promotes secondary infections.

Slide 20 · Kwashiorkor: Protein-predominant depletion

Relatively severe protein deficit

Visceral protein stores fall

Albumin synthesis decreases

Plasma oncotic pressure declines

Fluid redistributes

Dependent or generalized edema

Edema can conceal loss of underlying lean tissue.

Slide 21 · Kwashiorkor: Recognizable phenotype

Peripheral or generalized edema and sometimes ascites.

Patchy pigmentation, desquamation and hypopigmentation of skin (“flaky paint”).

Pale or alternating hair bands, fragility and reduced scalp attachment.

Apathy, anorexia and an enlarged fatty liver.

Slide 22 · Why a fatty liver develops in kwashiorkor

Protein deficiency

Lipoprotein apoprotein synthesis falls

Lipid export declines

Triglycerides retained by hepatocytes

Hepatic steatosis

Enlarged fatty liver

Hepatic steatosis is a characteristic distinction from uncomplicated marasmus.

Slide 23 · Intestinal injury in kwashiorkor

Crypt proliferative activity falls

Epithelial renewal slows

Villus / microvillus atrophy

Reduced absorptive surface

Disaccharidase deficiency

Transient milk intolerance

Potentially reversible mucosal changes with treatment.

Slide 24 · Hematologic effects of severe malnutrition

Bone marrow may become hypoplastic, particularly in the erythroid lineage.

Anemia has multiple potential contributors: Protein, iron, folate and inflammation.

Peripheral red cells may be microcytic, normocytic or macrocytic.

Peripheral blood morphology reflects the dominant combination of deficiencies.

Slide 25 · Immune and developmental consequences

Thymic and lymphoid atrophy correlate with reduced immune competence.

Infections increase demands and may accelerate nutritional deterioration.

Growth faltering and developmental impairment may persist beyond acute illness.

Severe early-life malnutrition can have neurologic consequences.

Slide 26 · Marasmus versus kwashiorkor

Characteristic

Marasmus

Kwashiorkor

Predominant deficit

Severe energy lack

Protein deficit relatively greater

Somatic tissue

Marked muscle and fat loss

Relative preservation, often obscured

Visceral protein / albumin

Relatively preserved

Substantially depleted

Edema

Generally not characteristic

Characteristic

Liver

Usually not fatty

Fatty enlargement

Skin / hair

Less characteristic changes

Flaky-paint skin; Hair changes

Slide 27 · Malnutrition in high-resource settings

Chronic illness, advanced age and immobility confer substantial risk.

Examine shoulders, upper limbs and thighs for loss of fat or muscle.

Ankle or sacral edema can coexist with severe tissue depletion.

Secondary malnutrition increases infection, wound-healing and postoperative risks.

Slide 28 · Inflammation-associated adult malnutrition

Cancer / chronic disease

Inflammatory mediators released

Metabolic adaptation

Energy expenditure and proteolysis increase

Muscle loss

Amino acids diverted to fuel generation

Muscle wasting may continue despite apparently adequate protein intake.

Slide 29 · Reduced intake versus cachexia

Feature

Predominantly reduced intake

Inflammation-related wasting

Principal driver

Substrate deprivation

Inflammatory, catabolic signaling

Muscle wasting

Energy adaptation

Often pronounced and persistent

Typical context

Dysphagia; Food insecurity

Advanced malignancy; Chronic disorders

Teaching implication

Correct intake and cause

Address illness-associated catabolism

Slide 30 · Eating disorders: Contrasting mechanisms

Disorder

Characteristic eating pattern

Key nutritional consequence

Anorexia nervosa

Severe restriction of intake

Marked weight loss and starvation effects

Bulimia nervosa

Binge episodes followed by purging

Fluid/electrolyte injury, often without severe low weight

Slide 31 · Anorexia nervosa: Multisystem starvation

Marked restrictive intake produces a severe malnutrition phenotype.

Bradycardia, cold intolerance, constipation and dry skin reflect endocrine adaptation.

Anemia, lymphopenia and hypoalbuminemia may occur.

Electrolyte abnormalities can result in life-threatening arrhythmias.

Slide 32 · Hypothalamic–gonadal suppression in anorexia

Severe energy restriction

Hypothalamic GnRH decreases

LH / FSH decrease

Reduced gonadal hormone production

Clinical consequence

Menstrual disturbance and bone loss

Low estrogen contributes to reduced bone mineral density.

Slide 33 · Anorexia: Bone marrow pathology

Marrow hematopoietic cellularity decreases during severe starvation.

An extracellular mucinous matrix may accumulate: Gelatinous transformation.

The source describes this feature as highly characteristic of anorexia nervosa.

MECHANISM MAP

Starvation

Hypocellular marrow

Mucinous stromal matrix

Reduced hematopoiesis

Slide 34 · Bulimia: The medical consequences of purging

Binge eating

Recurrent excess intake

Vomiting / laxative misuse

Fluid and electrolyte losses

Hypokalemia

Arrhythmia vulnerability

Repetitive vomiting may also produce aspiration and esophageal injury.

Slide 35 · Anorexia and bulimia: Clinical distinctions

Finding

Anorexia nervosa

Bulimia nervosa

Body weight

Often severely reduced

May remain near expected range

Menstrual changes

Common suppression

Irregularity; Amenorrhea less common

Major mechanism

Starvation / endocrine adaptation

Recurrent purging injury

Potential emergency

Cardiac arrhythmia

Arrhythmia; Aspiration; Rupture

Slide 36 · Vitamin deficiencies: Classification

Thirteen vitamins are required for normal human physiology.

Fat-soluble vitamins are A, D, E and K; Storage is generally more substantial.

Water-soluble vitamins include B-group vitamins and ascorbic acid.

Deficiencies may be dietary or secondary to abnormal absorption or metabolism.

Slide 37 · Why solubility matters

Property

Fat soluble

Water soluble

Members

A, D, E, K

B vitamins and C

Body storage

Often larger stores

Generally more limited stores

Malabsorption risk

Fat malabsorption particularly important

Variable by transport / disease

Example deficiency

Night blindness; Rickets

Beriberi; Scurvy

Slide 38 · Vitamin A: Functions and target tissues

Retinal

Photopigment formation in vision

Retinoic acid

Epithelial growth and differentiation

Retinoid signaling

Regulation of cellular responses

Vitamin A deficiency affects vision and the integrity of specialized epithelia.

Slide 39 · Vitamin A in the visual cycle

11-cis-retinal + opsin

Rhodopsin pigment

Light exposure

Retinal photoisomerization

Signal transduction

Visual nerve signal

Recycling

Chromophore regenerated

Insufficient vitamin A impairs dark adaptation and produces night blindness.

Slide 40 · Vitamin A deficiency: Morphology and function

Night blindness reflects impaired rhodopsin-dependent vision.

Conjunctival and corneal dryness may progress to xerophthalmia and ocular injury.

Abnormal epithelial differentiation predisposes to squamous metaplasia.

Defective epithelial barriers and immune function increase infection risk.

Slide 41 · Vitamin D: An endocrine nutrient

Skin / dietary sources

Vitamin D precursor

Liver hydroxylation

25-hydroxyvitamin D

Kidney hydroxylation

1,25-dihydroxyvitamin D

Target organs

Intestinal Ca and phosphate handling

Vitamin D supports bone mineralization through calcium/phosphate homeostasis.

Slide 42 · Vitamin D deficiency: The fundamental lesion

Impaired mineral availability causes excess unmineralized osteoid.

In children, mineralization failure disrupts the growth plate: Rickets.

In adults, mineralization failure affects existing bone: Osteomalacia.

Biochemical and skeletal findings must be interpreted together.

Slide 43 · Rickets: Disturbed growth-plate sequence

Poor provisional calcification

Cartilage fails to mature normally

Disorganized metaphysis

Cartilage and osteoid persist

Weak bone

Expansion and deformity under load

Rachitic rosary, metaphyseal enlargement and skeletal bowing arise from weak mineralization.

Slide 44 · Rickets versus osteomalacia

Feature

Rickets

Osteomalacia

Patient context

Growing skeleton

Mature skeleton

Principal site

Growth plate and metaphysis

Newly deposited osteoid

Structural effect

Growth-plate disruption and deformity

Poorly mineralized bone; Fragility

Shared basis

Vitamin D–related mineralization failure

Vitamin D–related mineralization failure

Slide 45 · Vitamins E and K: High-yield effects

Vitamin

Major physiologic role

Deficiency consequence

Vitamin E

Lipid-phase antioxidant

Neurologic dysfunction; Hemolytic anemia

Vitamin K

γ-carboxylation of clotting proteins

Bleeding tendency

Clinical context

Fat absorption matters

Fat absorption and gut availability matter

Slide 46 · Thiamine (B1): Energy metabolism

Thiamine deficiency

Reduced thiamine pyrophosphate

Oxidative metabolism

Impaired coenzyme-dependent reactions

Tissue dysfunction

Neurologic and cardiovascular syndromes

Beriberi and Wernicke–Korsakoff syndrome are the characteristic associations.

Slide 47 · Niacin deficiency: Pellagra

Niacin contributes to NAD and NADP-dependent oxidation–reduction reactions.

Pellagra classically produces dermatitis, diarrhea and dementia.

These organ systems are sensitive to altered intermediary metabolism.

The constellation, not a single isolated sign, suggests the deficiency.

Slide 48 · B6, B12 and folate: Contrasting syndromes

Nutrient

Biochemical role

Typical deficiency effect

Pyridoxine (B6)

Enzyme cofactor in intermediary reactions

Dermatitis; Glossitis; Neuropathy

Cobalamin (B12)

DNA synthesis / folate metabolism

Megaloblastic anemia; Spinal cord injury

Folate

One-carbon transfer for DNA synthesis

Megaloblastic anemia; Neural tube defects

Slide 49 · Vitamin C: Why collagen loses strength

Ascorbate deficiency

Prolyl / lysyl hydroxylation impaired

Unstable procollagen

Deficient collagen maturation

Weak connective tissue

Hemorrhage and poor wound healing

Scurvy is fundamentally a defect of stable collagen formation.

Slide 50 · Scurvy: Morphology explains the symptoms

Fragile connective tissue permits skin and mucosal hemorrhages.

Gingival changes and poor wound healing reflect reduced collagen integrity.

Defective osteoid matrix can produce bone abnormalities in growing children.

Capillary fragility and connective-tissue weakness provide the unifying mechanism.

Slide 51 · Trace-element deficiency: Organ consequences

Element

Main physiologic role

Deficiency-associated pathology

Iron

Hemoglobin and metalloenzymes

Microcytic hypochromic anemia

Iodine

Thyroid hormone synthesis

Goiter; Hypothyroidism

Zinc

Multiple enzyme functions

Periorificial dermatitis; Poor healing

Copper

Oxidases / connective tissue functions

Anemia; Neurologic abnormalities

Selenium

Glutathione peroxidase

Myopathy; Cardiomyopathy

Slide 52 · Micronutrient deficiency: Diagnostic localization

Ocular and epithelial abnormalities suggest vitamin A depletion.

Bone and growth-plate changes suggest mineralization deficits.

Anemia morphology guides consideration of iron, B12 and folate deficits.

Hemorrhage and poor wound healing suggest defects in vitamin C or vitamin K pathways.

MECHANISM MAP

Eye / epithelium

Bone / growth plate

Blood / marrow

Connective tissue

Slide 53 · Obesity is a disorder of energy homeostasis

Body weight reflects long-term integration of nutrient intake and expenditure.

Hypothalamic neuroendocrine networks respond to peripheral energy signals.

Genetic, environmental and behavioral factors modulate these pathways.

Central adiposity has prominent cardiometabolic consequences.

Slide 54 · Three components of energy regulation

Afferent signals

Adipose, gut and pancreatic hormones

Central integration

Hypothalamic arcuate networks

Efferent response

Food intake and energy expenditure

The system generates anorexigenic and orexigenic responses to energy state.

Slide 55 · Peripheral appetite signals

Signal

Principal origin

Textbook action

Leptin

Adipocytes

Signals energy sufficiency; Reduces intake

Ghrelin

Stomach

Promotes hunger / food intake

PYY

Intestine

Postprandial satiety signaling

GLP-1 and GIP

Enteroendocrine cells

Meal-related gut signals

Insulin

Pancreatic β cells

Energy-status / anorexigenic signaling

Slide 56 · Hypothalamic pathways: Opposite effects

Circuit

Mediators

Physiologic direction

Anorexigenic

POMC / CART → α-MSH → MC3/4R

Decreased food intake; Higher expenditure

Orexigenic

NPY / AgRP → Y1 / Y5

Increased intake; Lower expenditure

Integration

Leptin, insulin, ghrelin and gut peptides

Balances circuit activity

Slide 57 · Leptin closes the energy-storage feedback loop

Adipose stores rise

Leptin secretion increases

Hypothalamic signal

POMC activated; NPY/AgRP inhibited

Behavior / metabolism

Appetite falls; Expenditure rises

Reduced stores produce the opposite regulatory response.

Slide 58 · Obesity: Genetic signaling and resistance

Rare disabling leptin or leptin-receptor variants can cause severe obesity.

Loss-of-function variants affecting melanocortin signaling also contribute.

Common obesity often features elevated leptin with diminished central response.

A high leptin concentration does not imply effective leptin signaling.

Slide 59 · Gut hormones help regulate meal timing

Ghrelin rises around hunger states and activates orexigenic hypothalamic pathways.

PYY and incretin peptides participate in postprandial signaling.

GLP-1 and GIP connect nutrient sensing to pancreatic and central regulation.

Meal-to-meal signals operate within the long-term adiposity feedback system.

Slide 60 · Adipose tissue as an inflammatory organ

Excess adiposity

Altered adipokines and lipid flux

Inflammation

Cytokines and inflammasome signaling

Insulin resistance

Metabolic dysregulation

Adipose tissue is biologically active, not merely an energy-storage depot.

Slide 61 · Obesity: Cardiometabolic consequences

Process

Associated complication

Pathophysiologic link

Insulin resistance

Type 2 diabetes mellitus

Impaired glucose regulation

Dyslipidemia

Atherosclerotic disease

Triglycerides ↑; HDL often ↓

Blood-pressure dysregulation

Hypertension

Neurohumoral and vascular effects

Visceral adiposity

Metabolic syndrome

Combined inflammation and risk factors

Slide 62 · Obesity: Organ-system manifestations

System

Representative consequence

Liver

Steatotic liver disease; Possible fibrosis

Gallbladder

Cholesterol-rich gallstones

Respiratory

Obstructive sleep apnea; Hypoventilation

Musculoskeletal

Degenerative joint disease

Cardiovascular

Increased atherosclerotic burden

Slide 63 · Mechanistic links between obesity and cancer

Insulin resistance

Hyperinsulinemia; IGF signaling

Hormonal effects

Altered estrogen availability

Inflammation / adipokines

Growth-supportive tissue signaling

Cancer association

Multiple organ sites

Several plausible mechanisms; A single mechanism is not established.

Slide 64 · Diet and carcinogenesis: Evidence boundaries

Dietary compounds may contain carcinogens or influence endogenous carcinogen formation.

Associations have been described between dietary patterns and organ-specific malignancies.

Mechanistic and epidemiologic evidence has important inconsistencies.

Robbins does not establish a single diet that reliably causes or prevents cancer.

Slide 65 · Dietary fats and atherogenesis

Fat composition

Saturated versus polyunsaturated fractions

Lipid response

Serum cholesterol may change

Vascular context

Atherogenic lipoproteins drive plaque risk

Separate changes in intermediate lipid markers from demonstrated clinical-event benefits.

Slide 66 · Diet composition beyond calorie count

Sodium restriction can reduce blood pressure.

Dietary fiber increases stool bulk and alters transit.

Metabolic and cardiovascular consequences depend on diet composition as well as energy intake.

Specific supplement claims require evidence from clinical outcomes, not mechanistic plausibility alone.

Slide 67 · Clinicopathologic synthesis

Nutrient imbalance

Insufficiency or excess

Cellular alteration

Defective synthesis or dysregulated signaling

Tissue lesion

Wasting, poor mineralization or steatosis

Clinical disease

Immunity, skeletal, metabolic or vascular injury

Start from the affected biochemical function, then explain the observed morphology.

Slide 68 · Application: An edematous malnourished child

CLINICAL PRESENTATION

A young child has restricted dietary diversity, generalized edema, pigmentary skin changes and hepatomegaly.

Which protein compartment is preferentially depleted—and why is the liver enlarged?

CLINICOPATHOLOGIC INTERPRETATION

Kwashiorkor pattern: Visceral protein depletion lowers albumin; Deficient lipoprotein synthesis favors hepatic triglyceride retention.

Slide 69 · Application: Obesity and systemic risk

CLINICAL PRESENTATION

An adult with central adiposity has hypertension, hypertriglyceridemia and impaired glucose regulation.

What shared disease process links these findings?

CLINICOPATHOLOGIC INTERPRETATION

Metabolic syndrome links insulin resistance, dyslipidemia, hypertension and chronic low-grade inflammatory signaling.

Slide 70 · Five clinicopathologic principles

Determine whether nutrient supply, absorption, storage, demand or regulation is abnormal.

Distinguish somatic muscle loss from visceral protein depletion.

Relate specific vitamin and mineral functions to affected tissues.

Treat adiposity as an endocrine and inflammatory condition.

Avoid attributing systemic disease to diet without considering evidence quality.

Slide 71 · Selected source

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026).

Chapter 9: Environmental and Nutritional Diseases, pp. 394–410.

Primary lecture scope: Nutritional Diseases and the contiguous sections on dietary insufficiency, severe acute malnutrition, vitamin deficiencies, obesity and diet-associated systemic disease.

Slides are original educational syntheses; diagrams are native PowerPoint schematics, not clinical specimens.